WO2024130044A1 - Treatment of psychological factors affecting other medical conditions (pfaomc) - Google Patents

Abstract

The present disclosure provides methods for treating psychological factors affecting other medical conditions (PFAOMC) in a subject by administering a reversible monoamine oxidase inhibitor (RIMA), for example moclobemide, optionally in combination with a second pharmaceutical agent, which may for example be an antihyperglycemic agent, an anti-hypertensive agent, an anti-inflammatory agent, an antioxidant, an anxiolytic agent, or an antidepressant, as well as certain other disclosed pharmaceutical agents. In some aspects, the combinations provide synergistic effects in the treatment of the psychological factor(s) and the medical condition(s). Also disclosed are pharmaceutical compositions and pharmaceutical kits comprising such agents and such combinations, including for use in treating subjects with PFAOMC.

Description

2023-12-14 TREATMENT OF PSYCHOLOGICAL FACTORS AFFECTING OTHER MEDICAL CONDITIONS (PFAOMC) INVENTORS: Igor Elman, Louis Herlands CROSS-REFERENCE [01] Priority is claimed under PCT Article 8(1) and Rule 4.10 to U.S. Provisional App. No.63/432,573, filed December 14, 2022, and incorporated by reference for all purposes as if fully set forth herein. FIELD OF THE INVENTION [02] The disclosure relates generally to methods of treating a subject with psychological factors affecting other medical conditions (PFAOMC) by administering a reversible monoamine oxidase inhibitor (RIMA), optionally together with a second pharmaceutical agent. In further aspects are pharmaceutical compositions and kits comprising a RIMA and an optional second agent, such as for use in treating PFAOMC. BACKGROUND OF THE INVENTION [03] Psychological factors affecting other medical conditions (PFAOMC) is a disorder that is diagnosed when clinically significant psychological or behavioral factors adversely affect an individual's underlying medical condition and increase the individual's risk for suffering, death, or disability from that condition (Am Psych Assoc.2022. Diagnostic and Statistical Manual of Mental Disorders , 5th ed., text rev.). [04] The frequent co-occurrence of medical and psychiatric morbidity has repeatedly been documented. This comorbidity leads to increased mortality and morbidity, loss of quality of life, and excess healthcare utilization through several psychosocial and biological mechanisms, including promotion of risk factors, amplification of somatic symptoms, nonadherence and noncompliance, adverse effects on the doctor-patient relationship and systems of care, and pathophysiologic effects. Yet, potentially treatable psychiatric symptoms in the medically ill, including such psychological factors, remain undiagnosed and undertreated. [05] PFAOMC can occur across the lifespan. A range of medical conditions can be affected by psychological factors, including those with a clear pathophysiology (e.g., diabetes, cancer, cerebrovascular disease, coronary artery disease, asthma, psoriasis, systemic lupus erythematosus, inflammatory bowel disease, helicobacter pylori infection, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), functional syndromes (e.g., migraines, irritable bowel syndrome, fibromyalgia), and idiopathic medical symptoms (e.g., insomnia, pain, fatigue, dizziness). Depending on the underlying (“other”) medical condition, the prognosis can vary significantly. Certain conditions include immediate medical consequences (e.g., myocardial infarction, takotsubo cardiomyopathy), while others include chronic consequences that persist over a long period of time (e.g., chronic occupational stress leading to increased risk for hypertension or denial of symptoms, denial of the need for treatment, and noncompliance with the recommended treatment plan and diagnostic work up resulting in heightened morbidity and mortality). 2023-12-14 [06] Currently, there are no safe and effective treatments for patients with PFAOMC, and particularly for those with insulin resistance and related disorders (IRARD), hypertension, and inflammatory disorders, as well as with additional other medical conditions. There is accordingly a need for treatments for such patients. [07] Provided herein are methods, compositions, and kits to meet this need and others, and having such advantages and improvements as will become readily appreciated through the disclosure below. INCORPORATION BY REFERENCE [08] Each cited patent, publication, and non-patent literature is incorporated by reference in its entirety, as if each was incorporated individually, and as if each is fully set forth herein. However, no such citation should be construed as an admission that a cited reference comes from an area that is analogous or directly applicable to the invention, nor should a citation be construed as an admission that a document or underlying information, in any jurisdiction, is prior art or forms part of the common general knowledge in the art. BRIEF SUMMARY OF THE INVENTION [09] The following presents a brief and simplified summary of some embodiments of the invention in order to provide a basic understanding thereof. It is not an extensive overview of the invention, nor intended to identify key or critical elements of the invention or to delineate its scope. Its sole purpose is to present some exemplary embodiments in a simplified form as a prelude to the more detailed description that follows. [10] In some aspects are disclosed methods of treating a psychological factor affecting other medical conditions (PFAOMC) in a subject in need thereof, comprising administering to the subject a therapeutic combination comprising a first agent and a second agent, including pharmaceutically acceptable salts thereof, wherein: the first agent is a reversible monoamine oxidase inhibitor (RIMA); and the second agent is any of an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, and an antihypertensive agent. [11] In some embodiments, the RIMA is any of moclobemide, brofaromine, caroxazone, eprobemide, metralindole, minaprine, and pirlindole. In some embodiments, the RIMA is moclobemide. [12] In embodiments, the second agent is an antihyperglycemic agent. In embodiments, the antihyperglycemic agent is any of an insulin, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an ɑ-glucosidase inhibitor, a DPP-4 inhibitor, a SGLT2 inhibitor, and a dopamine receptor agonist. In embodiments, the antihyperglycemic agent is any of insulin glulisine, aspart, or lispro, regular insulin, NPH insulin, glipizide, glyburide, gliclazide, glimepiride, repaglinide, nateglinide, metformin, rosiglitazone, pioglitazone, acarbose, miglitol, voglibose, sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin, dapagliflozin, canagliflozin, and bromocriptine. In embodiments, the antihyperglycemic agent is metformin. [13] In embodiments, the second agent is an antioxidant. In embodiments, the antioxidant is any of ascorbic acid, glutathione, a flavonoid, alpha lipoic acid, beta-carotene, alpha-tocopherol, ubiquinone, lycopene, coenzyme Q10, ellagic acid, retinol, masoprocol, pramipexole, nitric oxide, allopurinol, pentoxifylline, melatonin, probucol, quercetin, acetylcysteine, N-acetylcysteine, acetyl-L-carnitine, and 2023-12-14 L-methylfolate. In some embodiments, the antioxidant is N-acetylcysteine. [14] In some embodiments, the second agent is an anti-inflammatory agent. In some embodiments, the anti-inflammatory agent is any of apremilast, prednisone, hydrocortisone, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, mefenamic acid, nabumetone, naproxen, tolmetin, piroxicam, celecoxib, etoricoxib, aspirin, naproxen, meloxicam, apremilast, an anti-cytokine agent, and a selective COX-2 inhibitor. In some embodiments, the anti-cytokine agent is any of adalimumab, etanercept, infliximab, and tocilizumab. In some embodiments, the selective COX-2 inhibitor is lumiracoxib. In some embodiments, the anti-inflammatory agent is ibuprofen. [15] In some embodiments, the second agent is an anxiolytic agent. In some embodiments, the anxiolytic agent is any of a benzodiazepine, an azapirone, an alpha blocker, a beta blocker, an antidepressant, a barbiturate, a nonbenzodiazepine sedative, a hypnotic, nefazodone, pregabalin, mirtazapine, and gabapentin. In some embodiments, the benzodiazepine is any of lorazepam, diazepam, alprazolam, clonazepam, chlordiazepoxide, and chlordiazepoxide/clidinium bromide. In some embodiments, the benzodiazepine is lorazepam. In some embodiments, the azapirone is buspirone. In some embodiments, the barbiturate is any of pentobarbital, phenobarbital, and amobarbital. In some embodiments, the hypnotic is any of zolpidem, zaleplon, and zopiclone. [16] In some embodiments, the second agent is an antidepressant. In embodiments, the antidepressant is any of a selective serotonin reuptake inhibitor (SSRI), a selective norepinephrine reuptake inhibitor (NRI), a serotonin and norepinephrine reuptake inhibitor (SNRI), a dual norepinephrine/dopamine reuptake inhibitor (NDRI), a tricyclic antidepressant (TCA), a noradrenaline and specific serotonergic antidepressant (NaSSA), a serotonin antagonist and reuptake inhibitor (SARI), and a norepinephrine-dopamine disinhibitor (NDDI). [17] In embodiments, the SSRI is any of fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, vortioxetine, and vilazodone. In embodiments, the NRI is atomoxetine or reboxetine. In embodiments, the SNRI is any of desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine. In embodiments, the NDRI is any of amineptine, bupropion, desoxypipradrol, dexmethylphenidate, difemetorex, diphenylprolinol, ethylphenidate, fencamfamine, fencamine, lefetamine, methylenedioxypyrovalerone, methylphenidate, nomifensine, O-2172, phenylpiracetam, pipradrol, prolintane, pyrovalerone, solriamfetol, tametraline, and WY-46824. In embodiments, the NDRI is bupropion. In embodiments, the TCA is any of amitriptyline, doxepin, clomipramine, nortriptyline, imipramine, desipramine, protriptyline, dosulepin, maprotiline, trimipramine, and amoxapine. In embodiments, the NaSSA is any of aptazapine, esmirtazapine, mianserin, mirtazapine, and setiptiline. In embodiments, the SARI is any of etoperidone, lorpiprazole, mepiprazole, nefazodone, and trazodone. In embodiments, the NDDI is any of agomelatine, fluoxetine, flibanserin, and mirtazapine. In embodiments, the antidepressant is any of amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine, phenelzine, tranylcypromine, isocarboxazid, selegiline, mirtazapine, nefazodone, 2023-12-14 trazodone, bupropion, a neurotropic agent, an adaptogen, an actoprotector, a nootropic, a eugeroic, a racetam, an antihypoxant, a cognitive enhancer, potassium orotate, asparkam, a psychedelic, solriamfetol, vilazodone, atomoxetine, milnacipran, dosulepin, duloxetine, escitalopram, venlafaxine, citalopram, fluoxetine, fluvoxamine, vortioxetine, reboxetine, sertraline, paroxetine, esketamine, ketamine, dextromethor- phan/bupropion, naltrexone/bupropion, and lithium. In embodiments, the antidepressant is solriamfetol. [18] In embodiments, the psychedelic is any of MDMA, paramethoxyamphetamine, a 2C-x compound, 4-bromo-2,5-dimethoxyphenethylamine (2C-B), a 3C-x compound, a DOx compound, 2,5-dimethoxy-4- methylamphetamine (DOI), 3,4,5-trimethoxyamphetamine (TMA), a tryptamine, a benzofuran, an iboga alkaloid, an ergoline, a lysergamide, a phenethylamine, a benzocyclobutene derivative, a NBOMe derivative, a NBOH derivative, a NBMD derivative, a NBF derivative, a phenylcyclopropylamine derivative, DMMDA, DMMDA-2, a benzoxazine, an empathogen, an entactogen, a cannabinoid, a harmala alkaloid, a beta-carboline, ayahuasca, salvinorin A, salvinorin B, a piperazine, myristicin, elemicin, cryogenine, an active constituent of a species of Heimia , atropine, scopolamine, hyoscyamine, psilocybin, psilocin, DMT, 5-MeO-DMT, LSD, ketamine, esketamine, an active constituent of a species of Solanaceae , and an active constituent of Amanita muscaria mushrooms. [19] In some embodiments, the antidepressant is a cognitive enhancer. In some embodiments, the cognitive enhancer is any of D-serine, L-serine, L-theanine, caffeine, creatine, bacopa monnieri, rhodiola rosea, panax ginseng, ginkgo biloba, tanakan, salvia officinalis, lavandulaefolia, centella asiatica, nicotine, noopept, piracetam, phenotropil, a cholinergic, an amphetamine, citicoline, choline bitartrate, alpha-GPC, ethomersol, bemithyl, pyrazidol, actovegin forte, glutamine, bemethyl, mildronate, phenibut, armodafinil, modafinil, and phenylpiracetam. In some embodiments, the cognitive enhancer is modafinil. [20] In some embodiments, the second agent is an antihypertensive agent. In some embodiments, the antihypertensive agent is any of nimodipine, a diuretic, a beta blocker, an ACE inhibitor, an angiotensin II receptor blocker, a calcium channel blocker, an alpha blocker, an alpha-2 receptor agonists, a combined alpha and beta blocker, a central agonist, a peripheral adrenergic inhibitor, and a vasodilator. In some embodiments, the antihypertensive agent is nimodipine. In some embodiments, the antihypertensive agent is a beta blocker. In some embodiments, the beta blocker is propranolol. [21] In some embodiments, the therapeutic combination comprises any of: moclobemide and metformin; moclobemide and nimodipine; moclobemide and propranolol; moclobemide and solriamfetol; moclobemide and modafinil; moclobemide and lumiracoxib; and moclobemide and ibuprofen. [22] In some embodiments, moclobemide is administered daily. In some embodiments, the daily dose of moclobemide is between 50 mg and 600 mg. In some embodiments, the daily dose of moclobemide is between 50 mg and 150 mg. In some embodiments, the daily dose of moclobemide is between 150 mg and 600 mg. In some embodiments, the daily dose of moclobemide is between 300 mg and 600 mg. [23] In some embodiments, moclobemide is administered daily for at least 1 week, at least 2 weeks, at 2023-12-14 least 3 weeks, at least 4 weeks, at least 5 weeks, at least 10 weeks, at least 15 weeks, at least 16 weeks, or at least 20 weeks. In some embodiments, moclobemide is administered daily for at least 16 weeks. [24] In some embodiments, the psychological factor is any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. In some embodiments, the maladaptive health behavior is any of denial of symptoms, poor adherence to medical recommendations, and medication nonadherence. [25] In some embodiments, the disclosed methods further comprise treating the other medical condition in the subject. In some embodiments, the other medical condition is any of an insulin resistance and related disorder (IRARD), hypertension, an inflammatory disorder, a sleep disorder, a musculoskeletal condition, a renal disorder, a hematological disorder, a neurodegenerative disorder, cancer, an allergy, an immunological condition, a neurological condition, an infection, a genetic disorder, an otolaryngological disorder, a pulmonary condition, a urinary or bladder disorder, a digestive disorder, a hepatic disorder, an ophthalmic condition, a dental or oral health issue, a vascular disorder, a gyneco- logical condition, a skin disorder, a rare disease, an endocrinopathy, and congestive heart failure. In some embodiments, the other medical condition is any of an IRARD, hypertension, and an inflammatory disorder. [26] In some embodiments, the other medical condition is an IRARD. In some embodiments, the IRARD is any of insulin resistance, glucoregulatory disorders, glucoregulatory disorders induced by treatment with mood stabilizers, glucoregulatory disorders induced by treatment with antipsychotics, glucoregulatory disorders induced by treatment with opioids, insulin resistance induced by pharmacotherapy, coronary artery disease, ischemic heart disease, obesity, stroke, being overweight, a genetic disorder, and polycystic ovary disease. In some embodiments, the glucoregulatory disorder is any of prediabetes, diabetes, metabolic syndrome, obesity, and dyslipidemia. [27] In some embodiments, the other medical condition is hypertension. In some embodiments, hypertension is any of primary hypertension, secondary hypertension, resistant hypertension, malignant hypertension, white coat hypertension, hypertensive urgency, and isolated systolic hypertension. In some embodiments, the malignant hypertension is a hypertensive emergency. [28] In some embodiments, the other medical condition is an inflammatory disorder. The method of claim 63, wherein the inflammatory disorder is any of acne vulgaris, acid reflux or heartburn, age-related macular degeneration (AMD), an allergy, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, appendicitis, arteritis, arthritis, skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation, intestinal inflammation, neuroinflammation, ocular inflammation, brain inflammation, long COVID, a food allergy, post-treatment lyme disease syndrome, an ulcer, asthma, atherosclerosis, autoimmune disorder, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, burns, bursitis, cancer, cardiovascular 2023-12-14 disease, celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, congestive heart failure, conjunctivitis, colitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, lacrimal inflammation, and dementia. [29] In some embodiments, the genetic disorder is either of Prader-Willi syndrome (PWS) and a Prader-Willi-Like syndrome. In some embodiments, the sleep disorder is any of insomnia, dyssomnia, and parasomnia. In some embodiments, the musculoskeletal condition is any of arthritis, osteoporosis, and dystonia. In some embodiments, the arthritis is any of osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathy, reactive arthritis, psoriatic arthritis, enteroarthritis associated with inflammatory bowel disease, Whipple and Behcet's disease, septic arthritis, gout, pseudogout, and Still's disease. In some embodiments, the spondyloarthropathy is ankylosing spondylitis. In some embodiments, the reactive arthritis is Reiter syndrome. In some embodiments, the gout is any of gouty arthritis, crystalline synovitis, and metabolic arthritis. In some embodiments, the pseudogout is calcium pyrophosphate deposition disease. In some embodiments, the renal disorder is renal failure. In some embodiments, the hematological disorder is any of anemia, a clotting disorder, and polycythemia vera. [30] In some embodiments, the neurodegenerative disorder is Alzheimer's disease or Parkinson's disease. In embodiments, the neurological condition is any of seizure disorder, head trauma, multiple sclerosis, and tremor. In embodiments, the infection is either of a helicobacter pylori infection and a pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection. In embodiments, the pulmonary condition is either of chronic obstructive pulmonary disease (COPD) and interstitial lung disease. In embodiments, the urinary or bladder disorder is any of urinary incontinence, interstitial cystitis, and benign prostatic hyperplasia. In embodiments, the digestive disorder is any of gastroesophageal reflux, chronic gastritis, and a peptic ulcer. In some embodiments, the hepatic disorder is any of cirrhosis, cholelithiasis, and hepatitis. In some embodiments, the otolaryngological disorder is either of chronic otitis media and Meniere's disease. In some embodiments, the ophthalmic condition is either of glaucoma and dry eye syndrome. In some embodiments, the dental or oral health issue is a temporomandibular joint disorder. In some embodiments, the vascular disorder is either of peripheral artery disease and venous insufficiency. In some embodiments, the gynecological condition is endometriosis. In some embodiments, the endocrinopathy is Cushing’s disease. In some embodiments, the cancer is an NF-κB-induced inflammatory cancer. [31] In some embodiments, the cardiovascular disease is any of endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart abnormalities, vascular inflammation, arterial occlusive disease, inflammatory cardiac hypertrophy, peripheral arterial disease, aneurysm, embolism, incision, pseudoaneurysm, vascular malformation, vascular nevus, thrombosis, varicose veins, stroke, cardiac arrest, and carditis. In some embodiments, the vascular inflammation is arteritis, phlebitis, or vasculitis. In embodiments, the arterial occlusive disease is arteriosclerosis or stenosis. [32] In some embodiments, the subject has a co-occurring mental health disorder. In some embodiments, 2023-12-14 the co-occurring mental health disorder is any of a depressive disorder, a mood disorder, an anxiety disorder, a trauma- or stressor-related disorder, obsessive-compulsive disorder (OCD), a neurocognitive disorder, a feeding or eating disorder, intermittent explosive disorder, an addiction disorder, a substance use disorder, an impulse control disorder, compulsive buying disorder, repetitive self-mutilation syndrome, a nonparaphilic sexual addiction or paraphilia, a personality disorder, and attention deficit hyperactivity disorder (ADHD). [33] In some embodiments, treating the psychological factor affecting other medical conditions in the subject results in an improvement in the psychological factor. In some embodiments, the improvement in the psychological factor is an improvement in any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. In some embodiments, the improvement in the psychological factor is determined using an outcome measure. [34] In some embodiments, the outcome measure is any of a physiological measure, a patient-centered outcome measure, a behavioral factor measure, or a psychodiagnostic or psychometric tool. In some embodiments, the psychodiagnostic or psychometric tool is any of the Structured Clinical Interview for DSM-5, the Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Daily Stress Inventory, the Perceived Stress Scale, the Profile of Mood States questionnaire, the Yale Food Addiction Scale, the Eating Disorder Examination Questionnaire, the Food Craving Inventory, the Yale-Brown Obsessive-Compulsive Scale, the Food Craving Questionnaires, the Three-Factor Eating Questionnaire, the Relationship Patterns Questionnaire, the Treatment Adherence Perception Questionnaire, the Reward Deficiency Syndrome Questionnaire, the Genetic Addiction Risk Severity (GARS) test, the Clinician-Administered PTSD Scale, and the Civilian Mississippi Post-Traumatic Stress Disorder (PTSD) Scale. [35] In some embodiments, treating the psychological factor affecting other medical conditions in the subject results in an improvement in the other medical condition. In some embodiments, the improvement in the other medical condition is an improvement in any of an insulin resistance and related disorder (IRARD), hypertension, an inflammatory disorder, a sleep disorder, a musculoskeletal condition, a renal disorder, a hematological disorder, a neurodegenerative disorder, cancer, an allergy, an immunological condition, a neurological condition, an infection, a genetic disorder, an otolaryngological disorder, a pulmonary condition, a urinary or bladder disorder, a digestive disorder, a hepatic disorder, an ophthalmic condition, a dental or oral health issue, a vascular disorder, a gyneco- logical condition, a skin disorder, a rare disease, an endocrinopathy, and congestive heart failure. In some embodiments, the improvement in the other medical condition is an improvement in any of an IRARD, hypertension, and an inflammatory disorder. [36] In some embodiments, the improvement in the other medical condition is determined using an outcome measure. In some embodiments, the outcome measure is any of a physiological measure, a patient-centered outcome measure, or a behavioral factor measure. [37] In some further aspects are disclosed pharmaceutical kits for treating a psychological factor affecting 2023-12-14 other medical conditions (PFAOMC) in a subject, comprising a first pharmaceutical composition and a second pharmaceutical composition, wherein: the first pharmaceutical composition comprises a RIMA, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient; and the second pharmaceutical composition comprises a second agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient; and wherein the second agent is any of an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, and an antihypertensive agent. [38] In some embodiments of a pharmaceutical kit, the second agent is any of metformin, nimodipine, propranolol, solriamfetol, modafinil, lumiracoxib, ibuprofen, a PDE-1 inhibitor, a PDE-2 inhibitor, a PDE-3 inhibitor, a PDE-4 inhibitor, a PDE-5 inhibitor, N-acetylcysteine, meldonium, acetyl-L-cysteine, phenylpiracetam, vitamin D, L-methylfolate, buspirone, an anticonvulsant, lorazepam, a benzodiazepine, lithium, a triptan, acamprosate, naltrexone, vivitrol, buprenorphine, and a barbiturate. [39] In some embodiments of a kit, the first agent and the second agent are any of: moclobemide and metformin; moclobemide and nimodipine; moclobemide and propranolol; moclobemide and solriamfetol; moclobemide and modafinil; moclobemide and lumiracoxib; and moclobemide and ibuprofen. [40] In some embodiments of a pharmaceutical kit, the RIMA is formulated for any of intravenous, intramuscular, subcutaneous, and oral administration. In some embodiments of a pharmaceutical kit, the second agent is formulated for any of intravenous, intramuscular, subcutaneous, and oral administration. [41] In some embodiments of a pharmaceutical kit, the RIMA is in unit dosage form. In some embodiments of a pharmaceutical kit, the unit dosage form is any of an immediate release, a controlled release, a sustained release, an extended release, and a modified release formulation. [42] In some embodiments of a pharmaceutical kit, the second agent is in unit dosage form. In some embodiments of a pharmaceutical kit, the unit dosage form is any of an immediate release, a controlled release, a sustained release, an extended release, and a modified release formulation. [43] In some embodiments, the method further comprises administering an additional active agent. In some embodiments, the pharmaceutical kit further comprises an additional active agent. In embodiments, the additional active agent is any of an amino acid, an antioxidant, an anti-inflammatory agent, an analgesic, an antineuropathic or antinociceptive agent, an antimigraine agent, an anxiolytic, an antidepressant, an antipsychotic, an anti-PTSD agent, a cannabinoid, a dissociative, an immunostimulant, an anti-cancer agent, an anti- emetic, an orexigenic, an antiulcer agent, an anticholinergic agent, an anti-ischemic agent, an anti- histamine, an antihypertensive, an anticonvulsant, an antiepileptic, a bronchodilator, a mood stabilizer, a neuroprotectant, a serotonergic agent, a neuroactive agent, a psychedelic, an entactogen or empathogen, an entheogen, a MAOI, a tryptamine, a terpene, a phenethylamine, a sedative, a stimulant, an opioid modulator, an NMDA receptor agent, a vitamin, an SSRI, a NRI, an SNRI, a NDRI, a TCA, a NaSSA, a SARI, a NDDI, a benzodiazepine, or a phosphodiesterase (PDE-1, PDE-2, PDE-3, PDE-4, or PDE-5) inhibitor. 2023-12-14 [44] In some further aspects are disclosed the use of the therapeutic combination of any of the foregoing embodiments to treat PFAOMC in a subject. [45] In yet further aspects are disclosed methods of treating a psychological factor affecting other medical conditions (PFAOMC) in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a RIMA, or a pharmaceutically acceptable salt thereof. [46] In some such embodiments, the RIMA is any of moclobemide, brofaromine, caroxazone, eprobemide, metralindole, minaprine, and pirlindole. In some such embodiments, the RIMA is moclobemide. [47] In some such embodiments, moclobemide is administered daily. In some such embodiments, the daily dose of moclobemide is between 50–600 mg. In embodiments, the daily dose of moclobemide is between 50–150 mg, between 150–600 mg, or between 300–600 mg. In some such embodiments, moclobemide is administered daily for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 10 weeks, at least 15 weeks, at least 16 weeks, or at least 20 weeks. [48] In some such embodiments, the psychological factor is any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. In some such embodiments, the maladaptive health behavior is any of denial of symptoms, poor adherence to medical recommendations, and medication nonadherence. [49] In some such embodiments, the method further comprises treating the other medical condition in the subject. In some such embodiments, the other medical condition is any of an IRARD, hypertension, and an inflammatory disorder. In embodiments, treating the psychological factor affecting other medical conditions in the subject results in an improvement in the psychological factor. In embodiments, treating the psychological factor in the subject results in an improvement in the other medical condition. [50] In some further aspects are disclosed the use of the pharmaceutical composition of any of the embodiments above comprising a RIMA, such as moclobemide, to treat PFAOMC in a subject. [51] The foregoing has outlined broadly and in summary certain pertinent features of the disclosure so that the detailed description of the invention that follows may be better understood, and so that the present contribution to the art can be more fully appreciated. Hence, this summary is to be considered as a brief and general synopsis of only some of the objects and embodiments disclosed herein, is provided solely for the benefit and convenience of the reader, and is not intended to limit in any manner the scope, or range of equivalents, to which the claims are lawfully entitled. Additional features of the invention are described hereinafter. It should be appreciated by those in the art that all disclosed specific compositions and methods are only exemplary, and may be readily utilized as a basis for modifying or designing other compositions and methods for carrying out the same purposes. Such equivalent compositions and methods will be appreciated to be also within the scope and spirit of the invention as set forth in the claims. [52] It will be appreciated that the headings in this document are used only to expedite its review by the reader. They should not be construed as limiting the invention in any manner. 2023-12-14 BRIEF DESCRIPTION OF THE FIGURES [53] To further clarify various aspects of the invention, a more particular description is rendered by reference to certain exemplary embodiments illustrated in the figures. It will be appreciated that these figures depict only illustrated embodiments of the invention and should not be considered limiting of its scope. They are merely provided as exemplary illustrations of certain concepts of some embodiments of the invention. [54] Certain aspects of the invention are therefore further described and explained with additional specificity and detail, but still by way of example only, with reference to the accompanying figures in which: [55] FIG.1 illustrates an interplay between physiological and psychological conditions present in a diagnosis of PFAOMC as it relates to brain function in a subject and pharmacotherapy, according to some embodiments of the disclosure. [56] FIG.2 illustrates an interplay between a stressor, a subject, and the subject’s external environment with a focus on PFAOMC, according to some embodiments of the disclosure. [57] FIG.3 illustrates exemplary independent, interactive, and common processes occurring between physiological factors and psychological factors in conjunction with a medical condition, such as diabetes. DETAILED DESCRIPTION OF THE INVENTION [58] While various aspects and features of certain embodiments are summarized above, the following detailed description illustrates several exemplary embodiments in further detail to enable a person having ordinary skill in the art to which the invention pertains (equivalently as shorthand, “one of skill”) to practice such embodiments, and to make and use the full scope of the invention claimed. The examples are provided for illustrative purposes and are not intended to limit the scope of the invention or its applications. [59] It will be understood that many modifications, substitutions, changes, and variations in the described examples, embodiments, applications, and details of the invention illustrated herein can be made by those of skill without departing from the spirit of the invention, or the scope of the invention as described in the claims, and the general principles defined herein may be applied to a wide range of aspects. Thus, the invention is not intended to be limited to the aspects presented, but is to be accorded the widest scope consistent with the principles and features disclosed. The description is designed to make such embodiments apparent to one of skill, in that embodiments will be both readily cognizable and readily creatable without undue experimentation, solely using the teachings herein and the general knowledge of the art. [60] While the methods described herein may include particular steps, it should be apparent that other methods including fewer, more, or different steps than those described are also within the scope of the invention. The described methods and uses of discussed and associated steps herein therefore should be understood as being provided for purposes of illustration, not limitation. It should be further understood that the specific order or hierarchy of steps in the methods and uses disclosed are only exemplary approaches. I. General Definitions and Terms [61] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include 2023-12-14 plural referents unless the context clearly dictates otherwise. While the term “one or more” may be used, its absence (or its replacement by the singular) does not signify the singular only. The terms “comprising,” “including,” “such as,” and “having” are intended to be inclusive and not exclusive (i.e., there may be other elements in addition to the recited elements). Thus, the term “including” as used herein means, and is used interchangeably with, the phrase “including but not limited to.” The term “or” is used herein to mean, and is used interchangeably with, the term “and/or,” unless context clearly indicates otherwise. [62] All numbers expressing quantities, properties, reaction conditions, and so forth, used to describe and claim certain embodiments, are to be understood as being modified by the term “about,” even where they are not so expressly modified, and as not being modified by the term “about,” even where they are so expressly modified. Each such number will be understood as being both modified and not modified by the term “about.” [63] In some embodiments, “about” refers to plus or minus five percent (±5%) of the recited unit of measure. In some embodiments, “about” refers to plus or minus ten percent (±10%) of the recited unit of measure. The term “substantially,” where it is applied to modify a feature or limitation herein, and where not otherwise defined or described, will be read in the context of the disclosure and in light of the knowledge in the art to provide the appropriate certainty, e.g., by using a standard recognized in the art for measuring the meaning of “substantially” as a term of degree, or by ascertaining the scope as would one of skill. [64] In some embodiments (equivalently as shorthand, “in embodiments”), numerical parameters set forth in the description and claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in embodiments may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements. [65] Generally, the nomenclature used and procedures performed herein are those known in fields relating to one or more aspects of the invention, such as biology, chemistry, pharmacology, neuroscience, and medicine, and are those that will be well known and commonly employed in such fields. Standard techniques and procedures will be those generally performed according to conventional methods in the art. [66] Unless defined otherwise, all technical and scientific terms herein have the meaning as commonly understood by one of skill. Certain definitions that may assist a reader in understanding the disclosed embodiments follow; however, it will be appreciated that these definitions are not intended to limit the scope of the invention, which is properly interpreted and understood by reference to the full description (as well as any plain meaning known to one of skill) in view of the language used in the claims. Further, all terminology used herein is for the purpose of describing particular embodiments only; it is not intended to be limiting. [67] “ACE inhibitor” (angiotensin-converting enzyme inhibitor) may refer to an agent that inhibits ACE and 2023-12-14 helps the body produce less angiotensin. ACE inhibitors help the blood vessels relax and open up, which, in turn, lowers blood pressure. Examples of ACE inhibitors include benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, and ramipril. [68] “Actoprotector” may refer to an agent that enhances body stability against physical loads without increasing oxygen consumption or heat production. [69] “Adaptogen” may refer to an agent that controls the compensatory-adaptive reactions of microorganisms to stressful effects and the development of cultures under non-optimal growth conditions. [70] “Addiction” may refer to a chronic, relapsing disorder characterized by uncontrollable or uncontrolled seeking, craving, and use of the object of the addiction, despite the possibility of adverse consequences. [71] “Agent” may refer to an agent that affects or modulates the activity of a target, such as a receptor. In embodiments, an agent is a ligand for a receptor and modulates the activity of the receptor. In embodiments, an agent binds to, blocks, activates, inhibits, or otherwise influences (e.g., via an allosteric reaction) activity at a given receptor system. Unless context clearly indicates otherwise, the term “agent” refers to a pharmaceutical agent; “agent” and “pharmaceutical agent” may be used interchangeably herein. [72] “Alexithymia” may refer to a characteristic inability to use appropriate words to describe emotions. [73] “Alpha blocker” or “α-blocker” may refer to an agent that lowers blood pressure by preventing norepinephrine from increasing arterial resistance. Alpha blockers include α1 blockers and α2 blockers. Exemplary α1 blockers include alfuzosin, doxazosin, terazosin, tamsulosin, and prazosin. Exemplary α2 blockers include atipamezole, efaroxan, idazoxan, yohimbine, rauwolscine, and phentolamine. [74] “Alpha-2 receptor agonist” or “α2 agonist” may refer to an agent which reduces blood pressure and stabilizes affective states in a subject by decreasing the activity of the sympathetic nervous system. Examples include brimonidine, clonidine, dexmedetomidine, guanfacine, lofexidine, methyldopa, naphazoline, tizanidine, and xylazine. [75] “Angiotensin II receptor blocker” may refer to an agent which blocks the effects of angiotensin, a peptide hormone that causes vasoconstriction and increases blood pressure. Examples of angiotensin II receptor blockers include candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. [76] “Anniversary reaction” may refer to a common psychological response to a big, often traumatic event that has happened in a subject’s life. [77] “Antihypoxant” may refer to an agent that helps to prevent or reduce the effects of hypoxia, which is a condition where the body or a part of the body is deprived of adequate oxygen supply. [78] “Anxiety” may refer to the apprehensive anticipation of future danger or misfortune accompanied by worry, distress, and/or somatic symptoms of tension ( see, e.g. , Elman et al. Front Psychiatry.2018;9:29). [79] “Baseline body weight” may refer to the body weight of a subject at the initiation of treatment. [80] “Beta blocker” or “β-blocker” may refer to an agent that lowers blood pressure by blocking effects of epinephrine, which results in a reduced heart rate and cardiac output. Exemplary beta blockers include 2023-12-14 acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nadolol, penbutolol, propranolol, nadolol, pindolol, labetalol, timolol, carteolol, carvedilol, oxprenolol, nebivolol, sotalol, pronethalol, alprenolol, esmolol, butoxamine, and ritodrine. [81] “Binge eating” may refer to a disorder wherein a person eats an amount of food larger than most people would eat in a similar period of time under similar circumstances. An occurrence of excessive food consumption is often accompanied by a sense of a lack of control. [82] “Calcium channel blocker” may refer to an agent which prevents calcium from entering the cells of the heart and arteries. Calcium channel blockers relax and broaden narrowed blood vessels, reduce heart rate, and lower blood pressure. Exemplary calcium channel blockers include amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, and verapamil. [83] “Central agonist” may refer to an agent which lowers heart rate and reduces blood pressure by blocking the signals from the brain to the nervous system that increase the heart rate and narrow blood vessels. Exemplary central agonists include methyldopa, clonidine, lofexidine, guanabenz, and guanfacine. [84] “Combined alpha and beta blocker” may refer to an agent having properties of both an alpha and a beta blocker. Exemplary combined alpha and beta blockers include propranolol, carvedilol, and labetalol. [85] “Cognitive enhancer” may refer to an agent that acts on the central nervous system to improve cognitive functions. Cognitive functions which may be improved following the use of a cognitive enhancer include memory, motivation, reward, and overall mental performance. Exemplary cognitive enhancers include nootropics and eugeroic agents. [86] “Chronic pain” may refer to a pain which persists over a long period of time and may be profoundly affected by psychological factors ( see, e.g. , Elman et al. Archives Gen Psych, 2011;68(1):12-20 ; Elman et al. Progress Neurobiol.2013;109:1-27 ; Elman et al. Frontiers Psych.2018;9:29). [87] “Conversion” may refer to a type of defense mechanism in which anxiety caused by psychological conflict is converted and expressed in a symbolic somatic manifestation. One or more neurological symptoms of various types may result. Motor symptoms include weakness or paralysis; abnormal movements, such as tremors, jerks, or dystonic movements; and gait abnormalities. Sensory symptoms include altered, reduced, or absent skin sensation, vision, or hearing. Episodes of apparent unresponsiveness with or without limb movements may resemble epileptic seizures, syncope, or coma. Other symptoms include reduced or absent speech volume, altered speech articulation, a sensation of a lump in the throat (globus), or diplopia. [88] “Demoralization” may refer to a dysphoric state characterized by a subject’s sense of disempowerment and futility. [89] “Diabetes” may refer to a disease characterized by a fasting plasma glucose concentration (FPG) of greater than 125 mg/dL. [90] “Disease phobia” may refer to a persistent, unfounded fear of suffering from a disease, with doubt 2023-12-14 remaining, despite examination and reassurance. It also includes the fear of inheriting or acquiring a disease. [91] “Diuretic” may refer to an agent which improves the body’s ability to excrete excess sodium and water. Diuretics also help control blood pressure and cardiac function. Exemplary diuretics include chlorthalidone, chlorothiazide, hydrochlorothiazide, indapamide, metolazone, amiloride hydrochloride, spironolactone, triamterene, furosemide, and bumetanide. [92] “Dyslipidemia” may refer to a condition wherein an abnormal concentration of lipids and lipoproteins are present in the blood. [93] “Exacerbation” may refer to an increase in the severity of a disease or any of its symptoms. [94] “Health anxiety” may refer to nonspecific dimensions of abnormal illness behavior, such as generic worries about illness, or concerns about pain and bodily preoccupations (accompanied by the tendency to amplify somatic sensations). [95] “Hyperglycemia,” or “hyperglycemic” may refer to a higher than normal fasting blood glucose concentration, usually 126 mg/dL or higher. Hyperglycemia commonly affects individuals with diabetes, but can also have causes that are not due to underlying disease. [96] “Hypochondriasis” may refer to a chronic mental illness characterized by a persistent fear of having a serious or life-threatening illness, despite few or no symptoms. [97] “Illness denial” may refer to a psychological response to one’s own illness and covers several phenomenological phenomena ranging from an unrealistic optimism to the complete denial of disease. For example, patients may deny urgency, seriousness, affect, personal relevance, responsibility, long-term prognosis (including the possibility of death), implications of the diagnosis, or the need for therapy. Denial is termed as maladaptive, for example, when it prevents the adoption of healthy behaviors and results in a delay in seeking medical care and nonadherence to therapies or lifestyle modification programs. [98] “Irritable mood” may refer to a feeling state characterized by reduced control over temper, which usually results in irascible verbal or behavioral outbursts, although the mood may be present without observed manifestation. It may be experienced as brief episodes, in particular circumstances, or it may be prolonged and generalized. The experience of irritability is always unpleasant for the individual, and overt manifestation lacks the cathartic effect of justified outbursts of anger. [99] “Mental health disorder” may refer to a condition in a subject that generally involves negative changes in emotion, mood, thinking, and/or behavior. A mental health disorder, where otherwise undefined, will in embodiments refer to the disorder as defined in the DSM-5; however, in other embodiments it may refer to a disorder as defined in the DSM-IV, or based on other clinically acceptable criteria, such as the ICD-10 or ICD-11, or on other diagnostic criteria known to and generally accepted by those of skill in the art. [100] “Metabolic hormones” may refer to hormones that are released by the endocrine system to regulate the metabolism networks of cells and organs in a subject. For example, metabolic hormones can be peptide based hormones that affect and regulate the metabolism networks of cells and/or organs in a subject (Elman 2023-12-14 et al. Neuropsychopharmacology .2006;31(10):2091-2120). Exemplary metabolic hormones include insulin, glucagon, ghrelin, cortisol, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine (peptide YY, PYY). [101] “Metabolic syndrome” may be defined in accordance with the American Heart Association and the National Heart, Lung, and Blood Institute Consensus Statement by satisfying three or more of the following criteria: (1) having a waist circumference greater than 88 cm for women, or greater than 102 cm for men; (2) having triglyceride levels greater than 150 mg/dL; (3) having high-density lipoprotein (HDL) levels greater than 40 mg/dL for men, or greater than 50 mg/d for women; (4) having a blood pressure greater than 130/85 mmHg; and (5) having a fasting plasma glucose (FPG) greater than 110 mg/dL ( see, e.g., Elman et al. Sci Rep.2020;10(1):5617). [102] “Modulate” or “modulation” as used herein with respect to an activity of cell membrane receptors and/or a quantifiable biological event, such as release of monoaminergic neurotransmitters, indicates the process of interfering with the activity or biological event. Examples of interfering with the activity or biological event comprise increasing, decreasing, or maintaining the activity and/or biological event, for example increasing, decreasing, or maintaining the release of monoaminergic neurotransmitters. [103] “Monoaminergic neurotransmitter” may refer to a neurotransmitter or neuromodulator that contains an amino group connected to an aromatic ring by a two-carbon chain (–CH ₂ -CH ₂ –). Monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, and tryptophan, by the action of aromatic amino acid decarboxylase enzymes. Exemplary monoamine neurotransmitters include histamine; glutamate; catecholamines, e.g., dopamine, norepinephrine, and epinephrine; tryptamines, e.g., serotonin (5-HT) and melatonin; trace amines, e.g., β-phenylethylamine (PEA), tyramine, tryptamine, and octopamine. [104] “Neuroactive agent” may refer to an agent which acts on the central nervous system, or is administered for purposes of alleviating symptoms of a brain disorder (e.g., a psychiatric disease). [105] “Oral glucose tolerance” may refer to a subject’s response to orally administered glucose by examin- ing the subject’s blood glucose levels. Glucose tolerance refers to the ability to dispose of a load of glucose. [106] “Obesity” may refer to a condition characterized by an abnormal or excessive accumulation of fat in the body. A BMI over 30 kg/m ² is an indication of obesity. [107] “Opioid modulator” refers to an agent that can produce both agonistic and (partial) antagonistic effects by binding to different opioid receptors, and therefore cannot be classified as one or the other alone. [108] “Persistent somatization” may refer to frequent and/or continuous occurrences of somatization, which is a tendency to experience and communicate psychological distress as bodily and organic symptoms, and to seek medical help for them. [109] “Peripheral adrenergic inhibitor” may refer to an agent which reduces blood pressure by inhibiting brain neurotransmitters. Exemplary peripheral adrenergic inhibitors include guanadrel, guanethidine, monosulfate, and reserpine. 2023-12-14 [110] “Psychological function” describes how emotions, brain functioning, life circumstances, intellect, thinking patterns, and level of consciousness affect mood and cognitive abilities. It also may refer to the ability to achieve goals within oneself and the external environment, in relation to a subject’s behavior, emotions, social skills, and overall mental health, for example. [111] “Prediabetes” may refer to a state of latent impairment of carbohydrate metabolism, in which the criteria for diabetes mellitus are not all satisfied. Prediabetes is sometimes controllable by diet alone. [112] “Selective COX-2 inhibitor” may refer to a type of non-steroidal anti-inflammatory drug (NSAID), which directly targets cyclooxygenase-2 (COX-2), an enzyme responsible for inflammation and pain. Exemplary COX-2 inhibitors include lumiracoxib, celecoxib, rofecoxib, and valdecoxib . [113] “Serotonergic agent” may refer to an agent which modifies the effects of serotonin in a subject by acting on neurotransmission pathways involving serotonin. [114] “Thanatophobia” may refer to the sense of dying (e.g., angor animi). [115] “Type A behavior” may refer to a ‘specific emotion action complex’ resulting from the encounter of individual predispositions with particular situations perceived as being stressful or challenging. The most relevant features of type A behavior include excessive involvement in work and activities subjected to deadlines, time urgency, rapid speech and movements, hostility, competitiveness, and desire for achievement. [116] “Vasodilator” may refer to an agent that causes blood vessels to dilate, reducing blood pressure. Exemplary vasodilators include hydralazine, hydrochloride, and minoxidil. [117] Still additional definitions and abbreviations are provided elsewhere herein. II. Therapeutic Methods [118] In some aspects, provided are methods of treating a subject with PFAOMC. In some aspects, disclosed methods of treatment include the administration of an agent that modulates monoaminergic neurotransmission, such as a reversible inhibitor of monoamine oxidase A (RIMA). In embodiments, disclosed methods are useful in treating PFAOMC in a subject. In embodiments, disclosed methods are useful in treating the other medical condition in a subject with PFAOMC. In embodiments, disclosed methods are useful in treating PFAOMC and the other medical condition in a subject. [119] In embodiments, disclosed methods are useful in treating PFAOMC in a subject, where treating PFAOMC also produces a benefit or an improvement in the other medical condition in the subject. [120] In embodiments, disclosed methods are useful in treating PFAOMC and the other medical condition in a subject, where treating PFAOMC in the subject also produces a further benefit or improvement in the other medical condition in the subject, beyond treating the other medical condition directly. [121] As used herein, the terms “subject,” “patient,” and “individual” are used interchangeably, and refer to any person for which a disclosed composition or method may be efficacious, or who otherwise may benefit from a disclosed composition or method. In general, all of the disclosed compositions and methods will be 2023-12-14 appreciated to be useful for all individuals for which they are described herein to treat, although individual variation is to be expected, and will be understood in view of the teachings herein and knowledge in the art. [122] In general, “treating” or “treatment” refers to treating a disease or disorder in a mammal, and preferably in a human, and includes causing a desired biological or pharmacological effect, such as: (a) preventing a disorder from occurring in a subject who may be predisposed to the disorder but has not yet been diagnosed with it; (b) inhibiting a disorder, i.e. arresting its development; (c) relieving a disorder, i.e., causing regression thereof; (d) protecting from or relieving a symptom or pathology caused by or related to a disorder; (e) reducing, decreasing, inhibiting, ameliorating, or preventing the onset, severity, duration, progression, frequency, or probability of one or more symptoms or pathologies associated with a disorder; and (f) preventing or inhibiting of a worsening or progression of symptoms or pathologies associated with a disorder or comorbid with a disorder. In embodiments, treatment includes prevention. In other embodiments, treatment does not include prevention. Other measures, benefits, and surrogate or clinical endpoints, alone or in combination, will be understood to one of skill in view of the teachings herein and knowledge in the art. A. Psychological Factors Affecting Other Medical Conditions (PFAOMC) [123] “Psychological factors affecting other medical conditions” or “PFAOMC” (sometimes also “PFAMC”) refers to a disorder that may be diagnosed when a general medical condition is adversely affected by psychological or behavioral factors. These factors may precipitate or exacerbate the medical condition, interfere with treatment, or contribute to morbidity and mortality. The presence of one or more clinically significant psychological or behavioral factors can adversely affect a medical condition by increasing the risk of suffering, death, or disability. [124] PFAOMC is diagnosed if the following three criteria are present: (A) a medical symptom or condition (other than a mental disorder) is present; (B) psychological or behavioral factors adversely affect the medical condition in at least one of the following ways: (1) the factors have influenced the course of the medical condition as shown by a close temporal association between the psychological factors and the development or exacerbation of, or delayed recovery from, the medical condition; (2) the factors interfere with the treatment of the medical condition (e.g., poor adherence); (3) the factors constitute additional well-established health risks for the subject; or (4) the factors influence the underlying pathophysiology, precipitating or exacerbating symptoms, or necessitating medical attention; and (C) the psychological and behavioral factors in criterion (B) are not better explained by another mental disorder (e.g., panic disorder, major depressive disorder, post-traumatic stress disorder) ( see, e.g. , Am Psych Assoc., 2022, DSM-5-TR). [125] Examples of psychological or behavioral factors include psychological distress, patterns of interpersonal interaction, coping styles, and maladaptive health behaviors (e.g., denial of symptoms or poor adherence to medical recommendations); others are known and are discussed elsewhere. [126] As it is used in relation to psychological factors or PFAOMC, the term “other medical condition” herein refers to the medical condition that is adversely affected by the psychological or behavioral factors 2023-12-14 underlying a diagnosis of or diagnosable PFAOMC. The factors may (among the other ways above), e.g., precipitate or exacerbate the other medical condition, interfere with treatment of the other medical condition, contribute to the morbidity and mortality of the other medical condition, or some combination of the foregoing. [127] A diagnosis of PFAOMC considers the variety of ways in which specific psychological or behavioral factors can adversely affect other medical conditions. Likewise, there are also effects of the medical condition on psychological function in patients (Levenson & Bledowski. Psychosomatic Medicine & PFAOMC. In Tasman et al. eds. Psychiatry .4th ed. John Wiley & Sons; 2015:Chapter 116). [128] The prevalence of PFAOMC is unknown, but it is thought to be more commonly diagnosed than conversion disorder and other somatic symptom disorders ( id ). For example, 27% of general medical patients display symptoms of irritability, and 21% of general medical patients display symptoms of demoralization, in the absence of any co-occurring mental health disorder (Fava et al. Psychol Med .2012; 42(2):401-407; Mangelli et al. J Clin Psych .2005;66(3):391-394) . Similarly, the prevalence of nonadherence to prescribed medication regimes is about 62% in patients with chronic pain, about 33% in patients with post-myocardial infarction, and about 14% of patients with insulin-resistance related impaired metabolic status ( see, e.g. , Gast A. et al. Systematic Reviews .2019;8(1)). Symptoms of PFAOMC which remain unaddressed can thus exacerbate known risks for medical conditions, influence how patients respond to their symptoms, reduce adherence, and negatively impact pathophysiology. Thus, there remains a need for methods of treatment for patients with PFAOMC. This need is among those solved by the present disclosure. [129] “Psychological factors of PFAOMC” or “psychological factors” refer to elements related to mental function, emotions, and behavior, which adversely affect the other medical condition or may arise in the context of a medical condition in the subject, which leads to a diagnosis of PFAOMC. [130] Examples of psychological or behavioral factors include psychological distress, patterns of interpersonal interaction, coping styles, maladaptive health behaviors (e.g., denial of symptoms or poor adherence to medical recommendations), symptoms of depression or anxiety, stressful life events, relationship styles, personality traits, stress coping styles, regression to dysfunctional patterns of behavior, anger, denial, bereavement, and conflict defense mechanisms. [131] Used herein, the terms “psychological factors of PFAOMC” and “psychological factors” also will refer to and include “behavioral factors of PFAOMC” and “behavioral factors,” unless context indicates otherwise. [132] In embodiments, the psychological factor is any of (i.e., selected from the group consisting of) psychological distress, patterns of interpersonal interaction, coping styles, and maladaptive health behaviors (e.g., denial of symptoms, poor adherence to medical recommendations, or medication nonadherence) ( see, e.g. , DSM-5-TR). In embodiments, the psychological factor is psychological distress. In embodiments, the psychological factor is a pattern of interpersonal interaction. In embodiments, the psychological factor is a coping style. In embodiments, the psychological factor is a maladaptive health behavior. [133] Where an item, such as an agent, is chosen from “any of” a list (i.e., a group) of items, or where an 2023-12-14 item, such as an agent, is “selected from a group consisting of” the items, it will be appreciated that the group is closed (i.e., is a Markush group); however, in some embodiments, multiple items, such as agents, may be selected together from the group, in that each such group may be considered to include the implied term “or a combination thereof” unless the words “only one of” are used. For each such group, the disclosure also expressly includes an embodiment wherein “only one of” the group of items, such as agents, is intended. [134] In embodiments, the psychological factor is any of impaired quality of life, health anxiety, thanatophobia, disease phobia, illness denial, persistent somatization, conversion symptoms, functional somatic symptoms secondary to a psychiatric disorder, anniversary reaction, demoralization, irritable mood, type A behavior, alexithymia, stressful life events, depression, general anxiety, anger, hostility, maladaptive health behaviors (e.g., non-adherence to a prescribed regimen), and hypochondriasis. [135] In embodiments, the psychological factor is any of anhedonia, emotional numbing, and affective flattening. In embodiments, the psychological factor is anhedonia. In embodiments, the psychological factor is emotional numbing. In embodiments, the psychological factor is affective flattening. [136] In embodiments, the psychological factor influences a cognitive process or the cognition of the subject (e.g., contextual processing, perception, attention, memory, problem-solving or decision-making, selective attention, divided attention, pragmatics, sustained attention, heuristics, biases, decisional conflict, goal-setting, or self-regulation) ( see, e.g ., Elman et al. Addiction Neuroscience .2023;7:100100). [137] In embodiments, the psychological factor influences an emotion of the subject (e.g., happiness, sadness, anger, fear, or disgust). In embodiments, the psychological factor influences a personality trait of the subject (e.g., risk-seeking, risk-aversive, novelty-seeking, conscientious, honest, dishonest, extraverted, agreeable, or neurotic). In embodiments, the psychological factor influences sensations and perceptions of the subject (e.g., sensory processing, illusions, or hallucinations). [138] In embodiments, the psychological factor influences the motivation of the subject (e.g., intrinsic motivation, extrinsic motivation, achievement motivation, affiliation motivation, urges, or craving). In embodiments, the psychological factor influences individual beliefs and attitudes of the subject (e.g., cognitive dissonance, attitude formation, change in attitude, stereotyping, prejudice, implicit bias, or discrimination). [139] In embodiments, the psychological factor influences perceptions of control of the subject (e.g., locus of control, learned helplessness, social influence, peer pressure, conformity, obedience, social or societal norms, social facilitation, stress coping, or resilience). In embodiments, the psychological factor influences a developmental factor of the subject (e.g., attachment style, self-concept, or identity). In embodiments, the developmental factor relates to Erikson’s stages of psychosocial development. In embodiments, the developmental factor relates to Piaget’s stages of cognitive development. [140] In embodiments, the psychological factor influences the self-esteem of the subject (e.g., self-efficacy or identity formation). In embodiments, the psychological factor influences the language and communication 2023-12-14 of the subject (e.g., verbal or nonverbal). In embodiments, the psychological factor influences interpersonal relationships (e.g., familial relationships, relationships with friends, relationships with romantic partners, relationships with work colleagues, or platonic relationships) of the subject. [141] In embodiments, the psychological factor influences the mental health of the subject (e.g., anxiety, depression, compulsions, obsessions, paranoia, narcissistic traits, histrionic traits, antisocial traits, shyness, schizoid traits, or immaturity). In embodiments, the psychological factor influences a health behavior of the subject (e.g., sick role, health beliefs, health-promoting behaviors, or health risk behaviors). [142] In embodiments, the psychological factor influences the body image of the subject (e.g., anorexia, bulimia, or dysmorphic perceptions). In embodiments, the psychological factor influences addictive behavior of the subject (e.g., substance abuse, gambling, excessive shopping, or excessive use of pornography). In embodiments, the psychological factor influences cross-cultural factors (e.g., cross-cultural influences on behavior and attitude, influence of (social) media, media literacy, cultural intelligence, adaptability to different cultures, cultural empathy, or cross-cultural communication). In embodiments, the psychological factor influences the learning and conditioning of the subject (e.g., classical conditioning, operant conditioning, fear conditioning, or observational learning). [143] In embodiments, the psychological factor influences a therapeutic factor (e.g., therapeutic alliance, transference, countertransference, or therapeutic techniques). In embodiments, the psychological factor influences ethical decision-making skills of the subject (e.g., informed consent or confidentiality). In embodiments, the psychological factor influences the subject’s ability to experience pleasure (e.g., reward deficiency) (Bowirrat et al. Psychol Res Behav Manag . 2023;16:4839-4857; Borsook et al. Neurosci Biobehav Rev .2016;68:282-297; Elman & Borsook. Neuron .2016;89(1):11-36; Elman et al. Prog Neurobiol . 2013;109:1-27). [144] In embodiments, the psychological factor disrupts compliance. A psychological factor that disrupts compliance includes: stigma, shame, or humiliation regarding the medical condition; helplessness or depression regarding the medical condition; mistrusting clinicians; or anger with clinicians or the medical condition ( see, e.g., Claxton et al. Clin Ther .2001;23(8):1296-1310). [145] Psychological factors, in general, as well as other specific psychological factors, will be appreciated by those of skill, in view of the teachings herein and general knowledge in the art ( see, e.g. , Porcelli et al. Psychological Factors Affecting Medical Conditions: A New Classification for DSM-V . Karger; 2007). [146] It will be readily appreciated that a subject may have more than one psychological factor that affects a medical condition. For example, in embodiments, a subject has two psychological factors, three psychological factors, four psychological factors, five psychological factors, or more than five psychological factors. In some embodiments, more than one psychological factor affects the other medical condition. Therefore, in embodiments, the two psychological factors, three psychological factors, four psychological factors, five psychological factors, or more than five psychological factors affect the other medical condition. 2023-12-14 [147] However, “treating a psychological factor” or “treating PFAOMC,” and similar terms, herein refers to treating a single psychological factor, unless context indicates otherwise, including where a subject may have more than one psychological factor. Nonetheless, among the advantages of the disclosure is that in some embodiments, the disclosed methods are useful to treat more than one psychological factor. In embodiments, the disclosed methods treat more than one psychological factor of a subject. For example, in embodiments, the disclosed methods will treat two psychological factors, three psychological factors, four psychological factors, five psychological factors, or more than five psychological factors. Additionally, in embodiments, the psychological factor, or the more than one psychological factor, will affect more than one medical condition, including two medical conditions, three medical conditions, or more than three medical conditions. B. Other Medical Conditions [148] In the DSM-5-TR, the essential feature characterizing PFAOMC is its pathophysiological overlap with the index medical condition, that is, the presence of psychological factors (e.g., distress) or behaviors (e.g., maladaptive behaviors, such as nonadherence) that adversely affect a general medical symptom or condition. Causality also can run in the opposite direction, i.e., a medical condition can worsen a psychological factor. [149] In some aspects, a disclosed method promotes avoidance of a vicious cycle wherein exacerbation of a medical condition provoked by psychological factors or behaviors produces additional deterioration in the medical condition, leading to further negative psychological symptomatology that may eventually produce a transition from mild to severe and extreme clinical course DSM-5-TR specifiers, for example resulting in the psychological symptomatology worsening from a psychological factor to a clinical diagnosis of a mental health condition, and/or the medical condition or any symptoms thereof increasing in severity or worsening. Thus, in embodiments, treating a psychological factor prevents the psychological factor from increasing in severity or worsening and leading to a clinical diagnosis of a mental health condition. In embodiments, treating a psychological factor prevents a medical condition from increasing in severity or worsening. [150] In embodiments, a disclosed method is useful for treating the other medical condition in a subject with PFAOMC. In embodiments, a disclosed method is useful for treating PFAOMC and the other medical condition in a subject. [151] In embodiments, the other medical condition is selected from the group consisting of IRARD, hypertension, and inflammatory disorders. In embodiments, the other medical condition is IRARD. In embodiments, the other medical condition is hypertension. In embodiments, the other medical condition is an inflammatory disorder. In embodiments, the other medical condition is an additional other medical condition. 1. Insulin Resistance and Related Disorders (IRARD) [152] In embodiments, a disclosed method is useful for treating IRARD in a subject with PFAOMC. [153] “Insulin resistance” may refer to a phenomenon wherein the cells of a subject fail to respond normally to the hormone insulin. Therefore, glucose in the blood cannot enter cells, thus causing 2023-12-14 hyperglycemia, and further, cells themselves cannot perform normal functions thereof due to a shortage of glucose. Insulin resistance most commonly occurs in conjunction with diabetes, but may result from other underlying causes. Exemplary disorders related to insulin resistance include glucoregulatory disorders (e.g., prediabetes, diabetes, metabolic syndrome, obesity, dyslipidemia) of any etiology (including glucoregulatory disorders induced by treatment with mood stabilizers, glucoregulatory disorders induced by treatment with antipsychotics (e.g., clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, cariprazine, lurasidone, iloperidone, brexpiprazole, asenapine, lumateperone, pimavanserin), and glucoregulatory disorders induced by treatment with opioids), insulin resistance induced by pharmacotherapy, coronary artery disease, ischemic heart disease, overweight, obesity, stroke, excessive stress, reduced number of function of insulin receptors, the pancreas’ failure to produce insulin, a genetic disorder, and polycystic ovary disease ( see, e.g. , Elman et al. Neuropsychopharmacol . 2006;31(10):2091-2120; Kurbanov et al. J Psychopharmacol .2012;26(9): 1244-1251; Taviera et al. J Psychopharmacol .2014;28(4):395-400; Guina et al. Human Psychopharmacol: Clinical & Experimental . 2017;32(4); and Elman et al. Sci Reports-Nature .2020;10:5617). [154] Emotions and behaviors can be regulated by monoaminergic neurotransmitters and metabolic hormones, such as insulin ( see, e.g. , Gu et al., Pharmaceuticals (Basel) .2022;15(10):1203). Certain emotional and behavioral habits may be influenced by modulating the concentrations of monoaminergic neurotransmitters in the brain in conjunction with improving glucoregulatory function ( id ). For example, monoaminergic neurotransmission may be enhanced by inhibiting a monoamine oxidase (MAO) enzyme (e.g., monoamine oxidase A (MAO-A)) ( see, e.g. , Shih et al., Pol. J. Pharmacol . 1999;51(1):25-9). Post-synaptic monoaminergic signal transduction may be further enhanced by improved insulin sensitivity and other aspects of glucoregulatory function ( see, e.g. , Shpakov et al., Future Sci OA .2015;1(3):FSO25). [155] Normatively, insulin secretion during physiologically determined anabolism restrains (i.e., increases refractoriness of) the dopaminergic hedonic and motivational neural pathways driving the consumption of palatable food (Elman et al., Neuropsychopharmacol . 2006;31(10):2091-120; Elman et al., Sci. Rep . 2020;10(1):5617). This metabolic restraint by insulin, however, is rendered inefficient by insulin resistance, which prompts further consumption of palatable food with high caloric content ( id ). This produces additional deterioration in the glucoregulatory mechanisms of affected subjects, which result in unhealthy eating patterns ( id ). Individuals may additionally experience PFAOMC in the context of an insulin resistance and related disorder (IRARD), wherein PFAOMC adversely affects the IRARD. For example, a subject diagnosed with hyperglycemia experiences distress, and consequently, impaired quality of life as a result of the diagnosis. The impaired quality of life experienced by the subject interferes with the course of their treatment for hyperglycemia, as the subject continues to consume foods with a high caloric content to alleviate distress, contrary to instructions given by their healthcare professional. The subject’s impaired quality of life is not better explained by another mental disorder, which suggests the existence of PFAOMC. 2023-12-14 [156] Psychological stress can adversely affect glucose control in subjects suffering from IRARD ( see, e.g., Elman et al. Neuropsychopharmacol .2006;31(10):2091-2120; Sharma et al., Cureus .2022 Sep;14(9): e29142). For example, glycemic control is poorer in diabetic subjects who have more perceived stress. In some embodiments, a disclosed method synergistically reduces stress and improves glycemic control. [157] In some embodiments, IRARD is selected from the group consisting of insulin resistance, glucoregulatory disorders (e.g., prediabetes, diabetes, metabolic syndrome, obesity, dyslipidemia), glucoregulatory disorders induced by treatment with mood stabilizers, glucoregulatory disorders induced by treatment with antipsychotics, glucoregulatory disorders induced by treatment with opioids, insulin resistance induced by pharmacotherapy, coronary artery disease, ischemic heart disease, obesity, stroke, overweight, a genetic disorder, and polycystic ovary disease. In some embodiments, IRARD is insulin resistance. [158] In some embodiments, IRARD is a glucoregulatory disorder. In some embodiments, the glucoregulatory disorder is prediabetes. In some embodiments, the glucoregulatory disorder is diabetes. In some embodiments, the glucoregulatory disorder is metabolic syndrome. In some embodiments, the glucoregulatory disorder is obesity. In some embodiments, the glucoregulatory disorder is dyslipidemia. [159] In some embodiments, IRARD is a glucoregulatory disorder induced by treatment with a mood stabilizer. In some embodiments, IRARD is a glucoregulatory disorder induced by treatment with an antipsychotic. In embodiments, IRARD is a glucoregulatory disorder induced by treatment with an opioid. [160] In some embodiments, IRARD is insulin resistance induced by pharmacotherapy. In some embodiments, IRARD is coronary artery disease. In some embodiments, IRARD is ischemic heart disease. In some embodiments, IRARD is obesity. In some embodiments, IRARD is a stroke. In embodiments, IRARD is overweight. In embodiments, IRARD is a genetic disorder. In embodiments, the genetic disorder is Prader-Willi syndrome or Prader-Willi-Like syndrome. In embodiments, IRARD is polycystic ovary disease. 2. Hypertension [161] In embodiments, a disclosed method is useful for treating hypertension in a subject with PFAOMC. “Hypertension” may refer to a medical condition of persistent elevated blood pressure in the arteries. A subject has hypertension if they have a systolic pressure of greater than 140 mm Hg and a diastolic pressure of greater than 90 mm Hg. Literature suggests that PFAOMC is particularly relevant as it relates to hypertension ( see, e.g. , Tasman A. et al, 2015). Symptoms of PFAOMC, such as blood pressure reactivity to stress, may influence progression of hypertension or prolong its treatment ( id ). [162] In some embodiments, hypertension is selected from the group consisting of primary hypertension, secondary hypertension, resistant hypertension, malignant hypertension (e.g., a hypertensive emergency), white coat hypertension, hypertensive urgency, and isolated systolic hypertension. [163] In embodiments, hypertension is primary hypertension. In embodiments, hypertension is secondary hypertension. In embodiments, hypertension is resistant hypertension. In embodiments, hypertension is malignant hypertension. In embodiments, hypertension is white coat hypertension. In embodiments, 2023-12-14 hypertension is hypertensive urgency. In embodiments, hypertension is isolated systolic hypertension. 3. Inflammatory Disorders [164] In embodiments, a disclosed method is useful for treating an inflammatory disorder in a subject with PFAOMC. The terms “inflammation” and “inflammatory disorder” may be used interchangeably herein, unless context dictates otherwise. Inflammation is an essential immune response to tissue insults such as microbial infection, acute injury, chemical irritants, or other such dysregulation of normal tissue functioning. The inflammatory process is a feature of the innate immune system, whereby molecular patterns of tissue damage are recognized and responded to by a variety of inflammatory agents, such as cytokines and chemokines. These inflammatory agents act directly to remove harmful stimuli and initiate various signaling responses to return damaged tissue to a state of homeostasis. Although this response is often self-terminating, the resolution of inflammation may fail for multiple reasons, extending the inflammation response into a chronic stage and thereby becoming an inflammatory disorder (Ahmed AU. Front Biol . 2011;6(4):274–281). Inflammatory disorders are often associated with or underlie a variety of pathological conditions, including major cardiovascular and neuropsychiatric disorders (Nichols CD. Cardiovasc Psychiatry Neurol .2009:475108). Recent evidence suggests that symptoms of PFAOMC, such as chronic stress, activate the immune response system in a subject and release increased amounts of pro-inflammatory mediators into the body, resulting in worsened inflammation ( see, e.g. , Koh, K.B., Stress & Somatic Symptoms, Biopsychosociospiritual Perspectives. Springer Nature Switz. AG.2018. Ch.5, 55–63.) [165] In embodiments, the inflammatory disorder is selected from the group consisting of acne vulgaris, acid reflux/heartburn, age-related macular degeneration (AMD), allergies, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, anti-NMDAR encephalitis, appendicitis, arteritis, arthritis (e.g., osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathy such as ankylosing spondylitis, reactive arthritis (Reiter syndrome), psoriatic arthritis, enteroarthritis associated with inflammatory bowel disease or Whipple and Behcet's disease, septic arthritis, gout (also known as gouty arthritis, crystalline synovitis, metabolic arthritis), pseudogout (calcium pyrophosphate deposition disease), and Still's disease), skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation, intestinal inflammation, neuroinflammation, ocular inflammation, brain inflammation, long COVID, a food allergy, post-treatment lyme disease syndrome, an ulcer, asthma, atherosclerosis, autoimmune disorder, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, a burn, bursitis, cancer (e.g., NF-κB-induced inflammatory cancer), cardiovascular disease (e.g., endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart abnormalities, vascular inflammation such as arteritis, phlebitis, and vasculitis, arterial occlusive disease such as arteriosclerosis and stenosis, inflammatory cardiac hypertrophy, peripheral arterial disease, aneurysm, embolism, incision, pseudoaneurysm, vascular 2023-12-14 malformation, vascular nevus, thrombosis, varicose veins, stroke, cardiac arrest, and carditis), celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, congestive heart failure, conjunctivitis, colitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, lacrimal inflammation, and dementia. [166] In embodiments, the inflammatory disorder is acne vulgaris. In embodiments, the inflammatory disorder is acid reflux/heartburn. In embodiments, the inflammatory disorder is age-related macular degeneration (AMD), In embodiments, the inflammatory disorder is allergies. In embodiments, the inflammatory disorder is allergic rhinitis. In embodiments, the inflammatory disorder is Alzheimer’s disease. In embodiments, the inflammatory disorder is amyotrophic lateral sclerosis. In embodiments, the inflammatory disorder is anemia. In embodiments, the inflammatory disorder is anti-NMDAR encephalitis. In embodiments, the inflammatory disorder is appendicitis. In embodiments, the inflammatory disorder is arteritis. In embodiments, the inflammatory disorder is arthritis. In embodiments, the inflammatory disorder is skin inflammation. In embodiments, the inflammatory disorder is muscle inflammation. In embodiments, the inflammatory disorder is tendon inflammation. In embodiments, the inflammatory disorder is ligament inflammation. In embodiments, the inflammatory disorder is bone inflammation. In embodiments, the inflammatory disorder is cartilage inflammation. In embodiments, the inflammatory disorder is lung inflammation. In embodiments, the inflammatory disorder is heart inflammation. In embodiments, the inflammatory disorder is liver inflammation. In embodiments, the inflammatory disorder is pancreatic inflammation. In embodiments, the inflammatory disorder is kidney inflammation. In embodiments, the inflammatory disorder is bladder inflammation. In embodiments, the inflammatory disorder is gastric inflammation. In embodiments, the inflammatory disorder is intestinal inflammation. In embodiments, the inflammatory disorder is neuroinflammation. In embodiments, the inflammatory disorder is ocular inflammation. In embodiments, the inflammatory disorder is brain inflammation. In embodiments, the inflammatory disorder is long COVID. In embodiments, the inflammatory disorder is a food allergy. In embodiments, the inflammatory disorder is post-treatment lyme disease syndrome. In embodiments, the inflammatory disorder is an ulcer. In embodiments, the inflammatory disorder is asthma. In embodiments, the inflammatory disorder is atherosclerosis. In embodiments, the inflammatory disorder is autoimmune disorder. In embodiments, the inflammatory disorder is balanitis. In embodiments, the inflammatory disorder is blepharitis. In embodiments, the inflammatory disorder is bronchiolitis. In embodiments, the inflammatory disorder is bronchitis. In embodiments, the inflammatory disorder is bullous pemphigoid. In embodiments, the inflammatory disorder is a burn. In embodiments, the inflammatory disorder is bursitis. In embodiments, the inflammatory disorder is cancer. In embodiments, the inflammatory disorder is cardiovascular disease. In embodiments, the inflammatory disorder is celiac disease. In embodiments, the inflammatory disorder is cellulitis. In embodiments, the inflammatory disorder is cervicitis. In embodiments, the inflammatory disorder is cholangitis. In embodiments, the inflammatory disorder is cholecystitis. In embodiments, the inflammatory 2023-12-14 disorder is chorioamnionitis. In embodiments, the inflammatory disorder is chronic obstructive pulmonary disease (COPD). In embodiments, the inflammatory disorder is cirrhosis. In embodiments, the inflammatory disorder is congestive heart failure. In embodiments, the inflammatory disorder is conjunctivitis. In embodiments, the inflammatory disorder is colitis. In embodiments, the inflammatory disorder is cyclophosphamide-induced cystitis. In embodiments, the inflammatory disorder is cystic fibrosis. In embodiments, the inflammatory disorder is cystitis. In embodiments, the inflammatory disorder is lacrimal inflammation. In embodiments, the inflammatory disorder is dementia . 4. Additional Other Medical Conditions [167] In embodiments, the other medical condition is selected from the group consisting of IRARD, hypertension, inflammatory disorders, and additional other medical conditions. In embodiments, the other medical condition is an additional other medical condition. Herein, an additional other medical condition refers to a medical condition other than IRARD, hypertension, or an inflammatory disorder. [168] Exemplary additional other medical conditions include sleep disorders (e.g., insomnias, dyssomnias, or parasomnias); musculoskeletal conditions (e.g., arthritis, osteoporosis, or dystonia); renal disorders (e.g., renal failure); hematological disorders (e.g., anemia, a clotting disorder, or polycythemia vera); neurodegenerative disorders (e.g., Alzheimer's disease or Parkinson's disease); cancer; allergies; immunological conditions; neurological conditions (e.g., a seizure disorder, head trauma, multiple sclerosis, or tremor); infections (e.g., helicobacter pylori infection or pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (Blum et al. Open J Immunol .2022;12(3):65-75)); genetic disorders (e.g., psychological factors may impact the expression and management of genetic conditions); pulmonary conditions (e.g., chronic obstructive pulmonary disease (COPD) or interstitial lung disease); urinary and bladder disorders (e.g., urinary incontinence, interstitial cystitis, or benign prostatic hyperplasia); digestive disorders (e.g., gastroesophageal reflux, chronic gastritis, or peptic ulcer); hepatic disorders (e.g., cirrhosis, cholelithiasis, or hepatitis); otolaryngological disorders (e.g., chronic otitis media or Meniere's disease); ophthalmic conditions (e.g., glaucoma or dry eye syndrome); dental and oral health issues (e.g., temporomandibular joint disorders); vascular disorders (e.g., peripheral artery disease or venous insufficiency); gynecological conditions (e.g., those affecting the tissue lining the uterus, such as endometriosis); skin disorders; rare diseases (e.g., various uncommon conditions that may have psychological components in their management and impact, such as Prader-Willi syndrome); endocrinopathy (e.g., Cushing's disease); and congestive heart failure . In embodiments, the additional other medical condition is any of the foregoing other medical conditions. [169] In embodiments, the other medical condition is a sleep disorder. In embodiments, the other medical condition is a musculoskeletal condition. In embodiments, the other medical condition is a renal disorder. In embodiments, the other medical condition is a hematological disorder. In embodiments, the other medical condition is a neurodegenerative disorder. In embodiments, the other medical condition is cancer. In 2023-12-14 embodiments, the other medical condition is allergies. In embodiments, the other medical condition is an immunological condition. In embodiments, the other medical condition is a neurological condition. In embodiments, the other medical condition is an infection. In embodiments, the other medical condition is a genetic disorder. In embodiments, the other medical condition is a pulmonary condition. In embodiments, the other medical condition is a urinary or bladder disorder. In embodiments, the other medical condition is a digestive disorder. In embodiments, the other medical condition is a hepatic disorder. In embodiments, the other medical condition is an otolaryngological disorder. In embodiments, the other medical condition is an ophthalmic condition. In embodiments, the other medical condition is a dental or oral health issue. In embodiments, the other medical condition is a vascular disorder. In embodiments, the other medical condition is a gynecological condition. In embodiments, the other medical condition is a skin disorder. In embodiments, the other medical condition is a rare disease. In embodiments, the other medical condition is endocrinopathy. In embodiments, the other medical condition is congestive heart failure. In some other embodiments, the other medical condition is postpartum depression or seasonal affective disorder. C. Co-Occurring Mental Health Disorders [170] In embodiments, a subject with PFAOMC also may have a co-occurring mental health disorder. [171] “Co-occurring mental health disorder” refers to a mental health disorder which a subject has in addition to both PFAOMC and the other medical condition. Examples of co-occurring mental health disorders include depressive disorders, mood disorders, anxiety disorders and anxiety-related disorders, schizophrenia and other psychotic disorders, stressor related disorders, obsessive-compulsive disorder (OCD), feeding and eating disorders, breathing-related sleep disorders, parasomnias, sexual dysfunctions, gender dysphoria, neurocognitive disorder, disruptive, conduct disorders, intellectual disabilities, addiction and substance use disorders (SUDs), autism spectrum disorder, trauma- and stressor-related disorders, dissociative disorders, somatic symptom and related disorders, impulse control disorder, compulsive buying disorder (alternatively for buying, “shopping” or “spending”), repetitive self-mutilation syndrome, a nonparaphilic sexual addiction or paraphilia, personality disorder, and attention deficit hyperactivity disorder (ADHD). [172] It will be readily appreciated that a subject may have symptoms of a mental health disorder (e.g., symptoms of depression). However, the symptoms may only rise to the level of psychological factors, and thus would be insufficient to receive a diagnosis of the mental health disorder (e.g., depression or a depressive disorder; for example, where a diagnosis requires five depression symptoms every day, nearly all day, for at least two weeks, and a subject has fewer than five such symptoms, or has such symptoms with lesser frequency or persistence). [173] Where a subject has symptoms of a mental health disorder sufficient to receive a diagnosis of the mental health disorder, or has received a diagnosis of the mental health disorder, the mental health disorder will be a co-occurring mental health disorder, and the symptoms will be those of the co-occurring mental health disorder, and not psychological factors of PFAOMC. However, in embodiments, a subject may have 2023-12-14 psychological factors that themselves do not rise to the level of or support a clinical diagnosis of a mental health disorder, together with a co-occurring mental health disorder diagnosed based on other symptoms (i.e., the psychological factors and the symptoms of the co-occurring mental health disorder are separate). [174] For example, when PFAOMC is diagnosed by applying the DSM-5 criteria, psychological factors should not rise to the level of diagnosis for a specific disorder; Criterion C provides that the psychological and behavioral factors (in Criterion B) are not better explained by another mental disorder (e.g., panic disorder, major depressive disorder, PTSD). However, where such symptoms do not rise to the level of diagnosis, a subject may be inadequately treated; for example, pharmacotherapy generally is not indicated for treating depressive symptoms or mood states (e.g., emptiness, anhedonia, hopelessness, or irritability), or minor (subsyndromal) depression, in the absence of a diagnosis such as major depressive disorder (MDD). [175] In embodiments, the co-occurring mental health disorder is selected from the group consisting of a depressive disorder, a mood disorder, an anxiety disorder, a trauma- or stressor-related disorder, OCD, a neurocognitive disorder, binge eating disorder, intermittent explosive disorder, an addiction disorder, an impulse control disorder, compulsive buying disorder, repetitive self-mutilation syndrome, a nonparaphilic sexual addiction or paraphilia, a personality disorder, and ADHD. [176] In embodiments, the co-occurring mental health disorder is a depressive disorder. In embodiments, the co-occurring mental health disorder is a mood disorder. In embodiments, the co-occurring mental health disorder is an anxiety disorder. In embodiments, the co-occurring mental health disorder is a trauma- or stressor-related disorder. In embodiments, the co-occurring mental health disorder is obsessive-compulsive disorder (OCD). In embodiments, the co-occurring mental health disorder is a neurocognitive disorder. In embodiments, the co-occurring mental health disorder is feeding or eating disorder such as binge eating disorder. In embodiments, the co-occurring mental health disorder is intermittent explosive disorder. In embodiments, the co-occurring mental health disorder is an addiction disorder. In embodiments, the co-occurring mental health disorder is an impulse control disorder. In embodiments, the co-occurring mental health disorder is compulsive buying disorder. In embodiments, the co-occurring mental health disorder is repetitive self-mutilation syndrome. In embodiments, the co-occurring mental health disorder is a nonparaphilic sexual addiction or paraphilia. In embodiments, the co-occurring mental health disorder is a personality disorder. In embodiments, the co-occurring mental health disorder is ADHD. [177] In some embodiments, the co-occurring mental health disorder is a mental health disorder due to the other medical condition. In some other embodiments, the co-occurring mental health disorder is not due to the other medical condition . D. Modulating Neurotransmission 1. Neurocircuitry of PFAOMC [178] Behaviors and mood are regulated by the homeostatic and reward systems of the brain ( see, e.g., Elman et al., Neuropsychopharmacol.31(10):2091-120; Kleinridders et al. Curr Nutr Rep .2019;8:83-91). The 2023-12-14 homeostatic system is regulated by metabolic hormones, and senses the current energy state of the body ( id ). The reward system is regulated by emotional and physiological stimuli. Evidence suggests that there is also a substantial functional and neurochemical overlap between physical and emotional stimuli (e.g., pain) ( see, e.g. , Elman et al. Prog Neurobiol .2013;109:1-27). The homeostatic and reward systems interact, and studies suggest that their dysregulation may be linked to PFAOMC (Kleinridders et al. Curr Nutr Rep . 2019;8:83-91). For example, loneliness encompasses a comprehensive set of systemic changes that can coincide with alterations in immunometabolism patterns and contribute to the development of cardiovascular, glucoregulatory and oncological morbidity ( see, e.g. , Bowirrat et al. Psychol Res Behav Manag . 2023;16:4839-4857). Improvements in PFAOMC, in relation to adherence to medical recommendations, are correlated with an improved BMI in opioid dependent subjects (Li et al. Front Psychiatry .2023;14:1247961). [179] Brain insulin resistance, for example, causes anxiety and depressive behavior and compromises the dopaminergic system. Thus, insulin resistance and reduced function of monoaminergic neurotransmitters are associated with behavioral abnormalities, and such effects can interfere with medical treatment. In some embodiments, modulating monoaminergic neurotransmission is useful to treat subjects with PFAOMC. [180] FIG.1 illustrates exemplary interactions between physiological measures, such as glucose control, and psychological measures, such as hedonic well-being, as they relate to parts of the brain involved in PFAOMC, according to some disclosed embodiments. For example, in a healthy subject, homeostasis in the brain results when there is stability across the subject’s physical and emotional states. A subject’s physical and emotional states are evaluated using physiological and psychological measures, respectively. In contrast, when a subject has a medical condition, the subject’s physical and emotional states are no longer in balance, resulting in a feed-forward cycle, such as allostasis. “Allostasis” refers to a process by which the body adjusts to stressors at the expense of compromising some important functions. Allostatic load may adversely affect a subject’s mental or emotional health, which may result in a diagnosis of PFAOMC if psychological factors exacerbate the medical condition. FIG.1 also illustrates an exemplary mechanism demonstrating the disclosed methods for treatment of PFAOMC, according to some disclosed embodiments. [181] For example, in embodiments, the disclosed methods affect a subject’s physical and emotional states. In embodiments, the disclosed methods have a greater effect on a subject’s physical state than the subject’s emotional state. In embodiments, the disclosed methods have a greater effect on a subject’s emotional state than the subject’s physical state. In embodiments, the disclosed methods improve physical symptoms experienced by a subject, which affect the subject’s physical state. In embodiments, the disclosed methods improve symptoms experienced by a subject, which affect the subject’s emotional state. In embodiments, the disclosed methods improve symptoms experienced by a subject, which affect the subject’s physical and emotional states. In embodiments, the disclosed methods improve one or more psychological factors in a subject. In embodiments, the disclosed methods improve one or more other medical conditions in a subject. In embodiments, the disclosed methods improve one or more psychological factors and one or 2023-12-14 more other medical conditions in a subject. [182] FIG.2 illustrates an exemplary schematic overview of the complex interplay that occurs among a stressor, a subject, and the subject’s external environment, with a focus on the concept of PFAOMC. In embodiments, the stressor is the medical condition. The stressor has two components, namely PFAOMC and the physical aspects associated with the medical condition. The stressor acts on the subject, and the subject’s external environment works to modulate the subject’s response to the stressor. The subject and the subject’s external environment are affected by PFAOMC and the physical aspects that come with the medical condition. To restore health, the subject must adapt to co-existing with the mixed mental/physical aspects induced by the stressor through recovery and habituation. If the subject does not adapt, the subject experiences allostatic load, which may result in manifestations of medical and/or psychiatric morbidities. [183] FIG.3 illustrates exemplary independent, interactive, and common processes of a medical condition, such as diabetes, for example. In embodiments, the course of a medical condition is affected by certain factors, including modulating variables, demographics, stress, drug metabolism, and neuropsychopathology. At the onset of a medical condition, physiological factors are independent from psychological factors. As time passes after diagnosis of the medical condition, physiological factors begin to interact more closely with psychological factors. Physiological factors eventually begin to act in common with psychological factors, which can intensify the medical condition and lead to a diagnosis of PFAOMC. [184] In embodiments, a disclosed method modulates the neurocircuitry involved in PFAOMC in a subject. In embodiments, modulating neurocircuitry involves modulating neurotransmission (e.g., monoaminergic neurotransmission) in the subject. [185] In embodiments, a disclosed method improves a subject’s mood. In embodiments, a disclosed method improves a subject’s mental health. In embodiments, a disclosed method improves a subject’s behavioral habits. In embodiments, a disclosed method improves a subject’s medication adherence. In embodiments, a disclosed method improves the amount of stress a subject experiences each day. [186] The prefrontal cortex, striatum, amygdala, and insula are involved in the complex neurocircuitry that underlies mechanisms associated with PFAOMC. In embodiments, a disclosed method modulates monoaminergic neurotransmission in any of a subject’s prefrontal cortex, striatum, amygdala, or insula, including combinations thereof, and in some embodiments, including all such regions. In embodiments, a disclosed method modulates monoaminergic neurotransmission in a subject’s prefrontal cortex. In embodiments, a disclosed method modulates monoaminergic neurotransmission in a subject’s striatum. In embodiments, a disclosed method modulates monoaminergic neurotransmission in a subject’s amygdala. In embodiments, a disclosed method modulates monoaminergic neurotransmission in a subject’s insula. [187] Prefrontal Cortex . In some embodiments, a disclosed method modulates the monoaminergic neurotransmission in the prefrontal cortex of a subject. Without being bound by theory, the prefrontal cortex (PFC) has an important role within the neural networks that regulate behavior and cognition. The PFC 2023-12-14 establishes a bridge between a stimulus and a response. This ultimately creates a bridge between the internal neural network world and the external world (Slachevsky et al. Prefrontal Cortex and Control of Behavior. In: Aboitiz & Cosmelli (eds), From Attention to Goal-Directed Behavior . Springer; 2009:231-248). [188] Deficits in the PFC and its related circuitry underlie a variety of neurological and psychiatric disorders. A healthy, functioning PFC is thought to display “cognitive control” in a subject, which results in controlled brain responses that are goal directed and flexible (Friedman & Robbins. Neuropsychopharmacol . 2022;47:72-89; Elman & Borsook. Neuro n.2016;89(1):11-36; Elman et al. Prog Neurobiol .2013;109:1-27). [189] The PFC mediates a range of cognitive control processes, including switching between tasks, stopping automatic responses, coordinating tasks, monitoring, and planning ( Diamond A. Annu Rev Psychol. 2013;64:135–68; Friedman. Cortex .2017;86:186–204 ). Literature shows that cognitive control is susceptible to pharmacological intervention and hence neuromodulation (Friedman & Robbins. op cit .2022;47:72-89). [190] In some embodiments, a disclosed method modulates monoaminergic neurotransmission in the prefrontal cortex of a subject, thereby treating PFAOMC in the subject. [191] Striatum . In some embodiments, a disclosed method modulates the monoaminergic neurotransmission in the striatum of a subject. The striatum is positioned at a site wherein glutamatergic input converges with innervation from midbrain dopamine neurons (Cox. Nat Rev Neurosci . 2019;20:482-494). The dopamine reward prediction error (RPE) signal and contextual processing (Elman & Borsook. Front Psychiatry . 2018;9:29; Elman et al. Front Neurosci .2020;14:604867; Elman et al. Add Neurosci .2023;7:100100) take part in the reinforcement learning mechanisms mediated by the striatum (Elman & Borsook. Neuron .2016;89(1):11-36; Elman et al. Prog Neurobiol .2013;109:1-27; Elman et al. Arch Gen Psychiatry .2011;68(1):12-20). The RPE may act as a reinforcement signal that modifies glutamatergic synaptic inputs to the striatum that are active during unexpected rewards (e.g., co-active with dopamine neurons). The striatum thus plays a central role in the process of learning which actions lead to reward and implementing those actions. [192] In some embodiments, a disclosed method modulates monoaminergic neurotransmission in the striatum of a subject, thereby treating PFAOMC in the subject. [193] Amygdala . In some embodiments, a disclosed method modulates the monoaminergic neurotransmission in the amygdala of a subject. To respond adaptively to threats and other stimuli in a changing environment, an organism must have a healthy, functioning amygdala (Elman & Borsook. Front Psych .2018;9:29). Without being bound by theory, the amygdala mediates many processes related to emotions and behaviors by processing the content of emotional stimuli and mediating aspects of the peripheral expression of the emotional response (Wood et al. Emotion .2014;14(4):693-700). The amygdala is composed of complex circuitry, including at least 13 different subnuclei. The most clearly defined subnuclei are the central, the basal, and lateral nuclei. The central nucleus is responsible for many aspects of the fear response (Ressler. Biol Psychiatry .2010;67(12):1117-1119), as research has shown that a lesion to this area 2023-12-14 eliminates conditioned fear (LeDoux, Curr Opin Neurobiol .1992;2:191-197). The lateral- and the basal nuclei are involved in learning processing (Ressler. Biol Psychiatry .2010;67(12):1117-1119). [194] The terms “emotional regulation” and “emotional modulation” refer to the types of regulatory processes that can control the physiological, behavioral, and experiential components of our affective responses (Gross & Thompson. Emotional Regulation: Conceptual Foundations . In: Gross (ed.) Handbook of Emotional Regulation . The Guilford Press.2007:3-24). Emotional regulation allows us to take action to cope with a distressing situation to create a positive outcome, change how we think about an emotion-evoking stimulus, or shift our attention to reduce an undesired emotion. Although humans have developed cognitive and social means for acquiring and representing fear and emotion, people still use phylogenetically shared mechanisms for fear expression (Hartley & Phelps. Neuropsychopharmacol .2009;35:136-146). [195] In some embodiments, a disclosed method modulates monoaminergic neurotransmission in the amygdala of a subject, thereby treating PFAOMC in the subject. [196] Insula . In some embodiments, a disclosed method modulates the monoaminergic neurotransmission in the insula of a subject. Without being bound by theory, the insula is a cortical region that is connected with salience detection, self-awareness, interoception, and pain processing (Elman et al. Prog Neurobiol . 2013;109:1-27). The insula is involved in integrating somatosensory, autonomic, and cognitive-affective information to guide a subject’s behavior, and the region acts as a hub for processing information related to the state of one’s body, cognition and mood (Christopher et al. Brain.2014;137(8):2143-2154). [197] “Interoception” encompasses the process by which one’s nervous system receives, integrates, and interprets sensory information such as physiological signals (e.g., heart rate, breathing, hunger, and pain), limbic inputs, and cognitive inputs. The insula is involved in integrating information used to adjust a subject’s behavior based on interoception, which in turn helps a subject form urges, feelings, drives, adaptive responses, and cognitive and emotional experiences (Rolls. Cell Mol Immunology .2023;20:1270-1276). [198] In some embodiments, a disclosed method modulates monoaminergic neurotransmission in the insula of a subject, thereby treating PFAOMC in the subject. 2. Monoaminergic Neurotransmission [199] Dopamine, glutamate, serotonin, and norepinephrine are monoaminergic neurotransmitters that are involved in the complex neurocircuitry that underlies mechanisms associated with PFAOMC. In some embodiments, a disclosed method modulates a subject’s monoaminergic neurotransmission. In some embodiments, a disclosed method modulates any of a subject’s dopaminergic, glutaminergic, serotonergic, and norepinephrinergic neurotransmission. In embodiments, a disclosed method modulates a subject’s dopaminergic neurotransmission. In embodiments, a disclosed method modulates a subject’s glutamatergic neurotransmission. In embodiments, a disclosed method modulates a subject’s serotonergic neurotransmission. In embodiments, a disclosed method modulates a subject’s norepinephrinergic neurotransmission. In embodiments, a disclosed method modulates any two or more of any of a subject’s 2023-12-14 dopaminergic, glutaminergic, serotonergic, and norepinephrinergic neurotransmission. In embodiments, a disclosed method modulates any three or more of any of a subject’s dopaminergic, glutaminergic, serotonergic, and norepinephrinergic neurotransmission. In embodiments, a disclosed method modulates all four of a subject’s dopaminergic, glutaminergic, serotonergic, and norepinephrinergic neurotransmission. [200] Dopamine . In some embodiments, a disclosed method modulates the dopaminergic neurotransmission of a subject. Without being bound by theory, dopamine influences reward, motivation and reinforcement, and dopamine release can promote adherence to treatment when a subject experiences positive outcomes that motivate continued compliance. Dopamine plays an important role in a variety of cognitive processes like cognitive control, reinforcement learning, and decision making (Chakroun et al. Nat Comm .2023;15:5369). Dopamine is also involved in motor control, mood, and pain perception (Rubí & Maechler. Endocrinology .2010;151(12):5570-5581). The brain releases dopamine when pleasant surprises are experienced, and such release helps one learn about the consequences of certain behaviors and actions (Bogacz. Comp Systems Bio Neuro .2020;9e53262). Such learning helps a subject choose actions based on predicted outcomes, a key part of decision-making and motivational control. Dopamine is not part of all forms of reward learning, but it causes goals to become ‘wanted’ in the sense of motivating a subject’s actions to achieve the goals (Martin et al. Neuron . 2010;68(5):815-834). Links may exist between PFAOMC and hyposensitivity of dopaminergic systems (Li et al. Front Psychiatry .2023;14:1247961; Elman et al. Sci Rep . 2020;10(1):5617; Elman et al. Neuropsychopharmacology .2006;31(10):2091-2120). Dopamine regulates pancreatic endocrine function (e.g., insulin release and insulin modulation), participates in the signaling of reward effects, and is engaged by physiological stimuli in reward circuits in the brain, which suggests that dopamine plays a role in some behavioral aspects of PFAOMC (Elman et al. Neuropsychopharmacol . 2006;31(10):2091-2120; Rubí & Maechler. Endocrinology .2010;151(12):5570-5581). [201] Glutamate . In some embodiments, a disclosed method modulates the glutamatergic neurotransmission of a subject. Without being bound by theory, glutamate is implicated in synaptic plasticity, learning, and memory, which enables a subject to encode and retain treatment-related information and adapt behavior based on feedback (Elman et al. Neuropsychopharmacology .2006;31(10):2091-2120; Breier et al, Synapse.1998;29:142-147; Elman & Borsook. Neurosci Biobehav Rev.2019;103:374-383). Glutamate is responsible for the brain’s ability to process and store information about the environment and direct behavior in response to the information. Excitatory neurons in the brain use glutamate, and the excitatory glutamatergic synapses have a unique synaptic plasticity. This robust plasticity feature is an essential mechanism of memory formation (Kennedy. Cold Spring Harb Perspect Biol. 2016;8(2):a016824). Glutamate’s role in plasticity includes long-term potentiation (LTP), regulation of spine density, and synaptic reorganization. Glutamate may be essential to the neuroplasticity in adapting to environmental stressors, like cognition, learning, and mood (Pal. Front Hum Neurosci.2021;15:722323). For example, synaptic plasticity is physiologically involved in stress, fear and emotional memory (Bazzari & Parri. Brain Sci .2019;9(11):300). 2023-12-14 [202] Serotonin . In some embodiments, a disclosed method modulates the serotonergic neurotransmission of a subject. Serotonin helps regulate virtually all human behavioral processes and other central nervous system (CNS) effects (Berger et al. Annu Rev Med.2009;60:355-366). Most serotonin is actually found outside of the CNS and influences a range of physiologic processes, while the small percentage of serotonin that is located in the CNS plays a role in mental health processes and mental health disorders (Lin et al. Clin Psychopharmacol Neurosci .2014;12(3):196-202). Brainstem serotonin neurons send projections in cortical, limbic, midbrain, and hindbrain regions; all brain regions express at least one of the fifteen different serotonin receptors (Berger et al. Annu Rev Med. 2009;60:355-366). Serotonin’s influence on behavioral processes like emotional and impulse control supports a subject’s ability to navigate the world (Kanen et al. Transl Psychiatry .2021;11(81)). Serotonin behavioral and neuropsychological effects include effects on mood, attention, perception, memory, anger, aggression, stress responses, appetite, addiction, and sexuality (Berger et al. Annu Rev Med.2009;60:355-366). [203] Norepinephrine . In some embodiments, a disclosed method modulates the norepinephrinergic neurotransmission of a subject. Without being bound by theory, norepinephrine mediates attention, arousal, and stress response which help a subject stay focused and motivated to follow a treatment regimen. Norepinephrine is a neurotransmitter that is implicated in processes that facilitate the processing of relevant versus irrelevant information (Berridge & Waterhouse. Brain Res Rev.2003;42:33-84). Norepinephrine is involved in regulating cortical function and also is connected in the pathophysiology of psychiatric disorders (Martino et al. Psychopharmacol (Berl).2008;197(1):127-136) as well as medical conditions including hypertension and obesity (Elman et al. Psychopharmacol .2004;176(3-4):369-375). Attention is important in the rapid recognition of reward cues and establishment of reward memories, and reward history reciprocally guides attention to reward stimuli. The locus coeruleus-norepinephrine system is involved in a variety of psychiatric conditions that are characterized by a disturbance in reward and attention (Zhang et al., Prog Neuropsychopharmacol Biol Psych .2023;125:110751). E. Outcome Measures [204] In embodiments, measures of therapeutic effect include any outcome measure, endpoint, effect measure, or measure of effect within clinical or medical practice or research which is used to assess the effect, both positive and negative, of an intervention or treatment, whether patient-reported (e.g., questionnaires, patient testimonies, etc.), based on other patient data (e.g., patient monitoring), gathered through laboratory tests such as blood work, urine samples, etc., through medical examination by a doctor or other medical professional, or by digital tools or means (e.g., electronic tools such as online tools, smartphones, wireless devices, biosensors, or health apps). [205] The term “outcome measure” may refer to data collected that is related to the treatment of a subject. The outcome measure may include one or more physiological measures, one or more patient-centered outcome measures (PCOMs), or one or more behavioral factor measures. 2023-12-14 [206] A measure may be a physiological measure. A physiological measure monitors the physical reaction of a subject (e.g., BMI, systolic/diastolic blood pressure, blood glucose level, biomarker concentration in blood). A measure may be a PCOM. A PCOM is an assessment of the patient’s beliefs, opinions and needs in relation to their treatment (e.g., patient-reported negative or positive effects relating to PFAOMC or the other medical condition). A measure may be a behavioral factor measure. A behavioral factor measure is a measure of specific behaviors of the subject (e.g., adherence to a prescribed medication regimen). [207] In embodiments, an outcome measure is a primary or a secondary outcome measure. “Primary outcome measure” refers to an outcome measure of greater relative importance, such as specified in a protocol. “Secondary outcome measure” refers to an outcome measure which may be more exploratory in nature, or for which effects may be too small to detect, but which are still of interest or valuable to assess. Because what is a “primary” as opposed to a “secondary” outcome measure may depend on circumstances and the goal(s) of a clinician or researcher, as well as a consideration of the totality of outcome measures used together for a particular purpose, reference herein to outcome measures as “primary” or “secondary” is suggestive only, and all outcome measures may be generally used and referred to as “outcome measures.” [208] In embodiments, improvements (e.g., in PFAOMC, in one or more psychological or behavioral factors, and/or in an underlying other medical condition) may be measured by monitoring or self-monitoring of a subject. In some embodiments, the result of a disclosed method is measured by monitoring the number or content of paper diaries submitted by a subject. In some embodiments, the result of a disclosed method is measured by monitoring the number or content of Internet-based diaries submitted by a subject. In some embodiments, the result of a disclosed method is measured by monitoring the scores on a survey taken by a subject. In some embodiments, the result of a disclosed method is measured by monitoring an available database wherein a subject tracks any psychological factors experienced. In some embodiments, the result of a disclosed method is measured by monitoring use of current technology, such as smartphones with applications which track any psychological factors experienced. [209] In embodiments, a measure of therapeutic effect, which may be an outcome measure, will include an assessment. “Assessment” may refer to any method used with a patient, whether before, during, after, or unrelated in time to a specific treatment protocol, to measure, estimate, or evaluate a nature, ability, symptom, disorder, or other characteristic of the patient, whether qualitatively or quantitatively, and whether performed by a clinician (e.g., an interview), by a patient his or herself (e.g., a self-reported questionnaire), by a third-party or by a computer, including a medical device (e.g., as such as defined by the FDA or other regulatory body) or other device (e.g., a medical sensor or biosensor, a watch or fitness tracker, or a “wearable”), and whether graded by a human decision-maker or an artificial intelligence, machine learning, or computer algorithm, and whether or not regulated as software as a medical device (SaMD). [210] An assessment may be computer-assisted, and other computer-assisted assessments may be performed besides the assessments above. The term “computer-assisted” in “computer-assisted 2023-12-14 assessment” means an assessment comprising the use of electronic tools such as online tools, smartphones, wireless devices, or health apps (in some such examples, also known as “digital phenotyping”). Computer-assisted assessment will include the use of an electronic psychiatric notes system, where relevant clinical information will be recorded for the duration of the therapy by a therapist interacting face-to-face with a patient, and will also include the use of computer systems where the therapist and patient interact virtually (either synchronously or asynchronously), as well as where a patient only interacts with a computer (“computer” broadly meaning any electronic tool suitable for such purposes, including desktop, laptop, and notebook computers; tablets, smartphones, and other mobile devices; watches, fitness trackers, and personal electronic devices; and the like). 1. Methods for Evaluating Improvement in Psychological Factors [211] In embodiments, improvements in psychological factors are monitored using an outcome measure. In embodiments, the outcome measure may be a physiological measure. In embodiments, the outcome measure may be a PCOM. In embodiments, the outcome measure may be a behavioral factor measure. [212] In embodiments, improvements in a psychological factor may be measured using psychodiagnostic and psychometric tools commonly employed by those skilled in the art. Examples of psychodiagnostic and psychometric tools include the Structured Clinical Interview for DSM-5 (SCID-5; see, e.g. , Am Psych Assoc. The Structured Clinical Interview for DSM-5® . Appi.org. Published 2017; see also, e.g. , Elman et al. Sci Rep. 2020;10(1):5617), the Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Daily Stress Inventory, the Perceived Stress Scale, the Profile of Mood States questionnaire, the Yale Food Addiction Scale, the Eating Disorder Examination Questionnaire, the Food Craving Inventory, the Yale-Brown Obsessive-Compulsive Scale, the Food Craving Questionnaires, the Three-Factor Eating Questionnaire, the Relationship Patterns Questionnaire, the Treatment Adherence Perception Questionnaire, the Reward Deficiency Syndrome Questionnaire, the Genetic Addiction Risk Severity (GARS) test (Blum et al. Psychol Res Behav Manag. 2023;16:4287-4291), the Clinician-Administered PTSD Scale, and the Civilian Mississippi Post-Traumatic Stress Disorder (PTSD) Scale, all of the foregoing known and used as will be ordinarily understood. For each of the psychodiagnostic and psychometric tools disclosed herein, it will be appreciated that such tools are generally known and employed by those in the art, and reference to such tools may be found in the art. [213] “Beck Depression Inventory” or “BDI” refers to a 21-question item, self-report rating inventory that measures characteristic attitudes and symptoms of depression ( see, e.g. , Beck, et al. Archives of General Psychiatry.1961;4:561-571). When the test is scored, a value of 0 to 3 is assigned for each answer, and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores are as follows: 0–9: indicates minimal depression; 10–18: indicates mild depression; 19–29: indicates moderate depression; and 30–63: indicates severe depression. [214] “Hamilton Rating Scale for Depression” or “HAM-D” refers to a multiple-item questionnaire used to 2023-12-14 provide an indication of depression and as a guide to evaluate recovery ( see, e.g. , Elman et al. Am. J. Addict.2010;19(4):332-9; Karlsgodt et al. Am. J. Drug Alcohol Abuse.2003;29(3):539-51; Elman et al. Am. J. Drug Alcohol Abuse.2001 May;27(2):193-202 ; Elman et al. Biol Psychiatry.2001;49(6):553-555 ; Elman et al. Drug Alcohol Depend.1999;56(1):39-45; Elman et al. J Psychopharmacol.2002;16(2);163-7). The original 1960 version contained 17 items (HDRS-17), but four other questions not added to the total score are used to provide additional clinical information. Each item on the questionnaire is scored on a 3- or 5-point scale, depending on the item, and the total score is compared to the corresponding descriptor. Assessment time is about 20 minutes. The National Institute for Health & Clinical Excellence of the UK established the levels of depression in relation to the 17 item HRSD compared with those suggested by the APA. The score provides the following indications: Not depressed: 0–7; Mild depression (subthreshold): 8–13; Moderate depression: 14–18; Severe depression: 19–22 and very severe depression: >23 ( see, e.g. , Hamilton M., J Neurology, Neurosurgery, Psych.1960;23(1):56–62; and Hamilton M., Br. J Med Psychol.1959;32:50-55). [215] “Hamilton Rating Scale for Anxiety” or “HAM-A” refers to a multiple-item questionnaire used to measure the severity of perceived anxiety symptoms. It consists of 14 symptom-defined elements, and caters for both psychological and somatic symptoms, comprising anxious mood; tension (including startle response, fatigability, restlessness); fears (including of the dark/strangers/crowds); insomnia; ‘intellectual’ (poor memory/difficulty concentrating); depressed mood (including anhedonia); somatic symptoms (including aches and pains, stiffness, bruxism); sensory (including tinnitus, blurred vision); cardiovascular (including tachycardia and palpitations); respiratory (chest tightness, choking); gastrointestinal (including irritable bowel syndrome-type symptoms); genitourinary (including urinary frequency, loss of libido); autonomic (including dry mouth, tension headache) and observed behavior at interview (restless, fidgety, etc.). Each item is scored on a basic numeric scoring of 0 (not present) to 4 (severe): >17/56 is taken to indicate mild anxiety; 25–30 is considered moderate–severe anxiety ( see, e.g. , Thompson E. Occupational Med .2015;65(7):601). [216] “State-Trait Anxiety Inventory” or “STAI” refers to a commonly used measure of trait and state anxiety ( Spielberger Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press ). The STAI is a psychological inventory consisting of 40 self-report items on a 4-point Likert scale. The STAI measures two types of anxiety: state anxiety and trait anxiety. Higher scores are positively correlated with higher levels of anxiety ( see, e.g ., Elman et al. Am. J. Addict.2010;19(4):332-9 ; Karlsgodt et al. Am. J. Drug Alcohol Abuse.2003;29(3):539-51). It can be used in clinical settings to diagnose anxiety and to distinguish it from depressive syndromes. It also is often used in research as an indicator of distress. Studies also have shown that it is a sensitive predictor of caregiver distress over time, and that it can vary with changes in support systems, health, and other individual characteristics. Scores range from 20 to 80, with higher scores correlating with greater anxiety. The creators of this test separated the different types of anxieties so both scales would be reliable. This means the S-anxiety scale would only measure S-anxiety, and the T-anxiety scale would only measure T-anxiety. 2023-12-14 [217] “Daily Stress Inventory” or “DSI” refers to a self-reported measure of stressors experienced during daily life (e.g., mundane hassles, strains, or annoyances associated with routine daily activities and transactions of everyday life). Daily stress is relatively minor, but has the potential to disrupt the flow of everyday life and add to overall levels of stress ( see, e.g., Elman et al. Am. J. Addict.2010;19(4):332-9 ; Tschibelu et al. J. Addict Dis.2011;30(1):81-87). [218] “Perceived Stress Scale” or “PSS-10” refers to a 10-item questionnaire originally developed by Cohen et al. (1983) widely used to assess stress levels in young people and adults aged 12 and above. It evaluates the degree to which a subject has perceived life as unpredictable, uncontrollable and overloading over the previous month. In each case, respondents are asked how often they felt a certain way on a five-point scale from ‘never’ to ‘very often’. Answers are then scored as follow: Never = 0; Almost never = 1; Sometimes = 2; Fairly often = 3; Very often = 4; To calculate a total PSS score, responses to the four positively stated items (items 4, 5, 7 and 8) first need to be reversed (i.e.0 => 4; 1 => 3; 2 => 2; 3 => 1; 4 => 0). The PSS score is then obtained by summing across all items. Higher scores indicate higher levels of perceived stress ( see, e.g. , Cohen et al. Journal of Health and Social Behavior.24(4), 385–396). [219] “Profile of Mood States questionnaire” or “POMS questionnaire” refers to a 65-item self-reported psychological instrument intended for use with adults age 18 and above ( see, e.g. , Tschibelu et al. J. Addict. Dis.2011;30(1):81-7 ; Karlsgodt et al. Am. J. Drug Alcohol Abuse.2003;29(3):539-51). The POMS assesses short-term mood states which are understood to be transient and frequently fluctuating. This scale was developed by McNair et al. (McNair et al. POMS Manual for the Profile of Mood States. Education and Industrial Testing Service; 1971). Advantages of using this assessment include the simplicity of administration and ease of participant understanding. POMS can be administered and measured through written or online forums. POMS measures six different dimensions of mood swings over a period of time. These include: Tension or Anxiety, Anger or Hostility, Vigor or Activity, Fatigue or Inertia, Depression or Dejection, Confusion or Bewilderment. A five-point scale ranging from "not at all" to "extremely" is administered by experimenters to patients to assess their mood states. There are two forms of the test; the long form that is administered primarily to adults, and the short form which is primarily administered to adolescents. Completion of the assessment can take 5–15 minutes, depending on the form. [220] “Yale Food Addiction Scale” or “YFAS” is the first measure designed specifically to assess signs of addictive-like eating behavior. The YFAS allows for a more systematic examination of the hypothesis that highly processed foods (e.g., French fries, milkshakes) might trigger an addictive process for certain people. The YFAS includes 25 items and translates the diagnostic criteria for substance dependence as stated in the DSM-IV (American Psychiatric Association, 2000) to relate to the consumption of calorie-dense foods (e.g., high in refined carbohydrates and fat). The scale includes items that assess specific criteria, such as diminished control over consumption, a persistent desire or repeated unsuccessful attempts to quit, withdrawal, and clinically significant impairment. The YFAS includes two scoring options: 1) a “symptom 2023-12-14 count” ranging from 0 to 7 that reflects the number of addiction-like criteria endorsed; and 2) a dichotomous “diagnosis” that indicates whether a threshold of three or more “symptoms” plus clinically significant impairment or distress has been met ( see, e.g. , Gerhardt et al., Appetite , 2009;52(2):430-436). [221] “Eating Disorder Examination Questionnaire” or “EDE-Q” is a 28-item self-reported questionnaire adapted from the semi-structured interview Eating Disorder Examination (EDE) and designed to assess the range and severity of features associated with a diagnosis of eating disorder using 4 subscales (e.g., Restraint, Eating Concern, Shape Concern, and Weight Concern) and a global score. The EDE-Q generates two types of data: frequency data on key behavioral features of eating disorders in terms of number of episodes of the behavior, and subscale scores reflecting the severity of characteristics of eating disorders. Subscales are Restraint, Eating Concern, Shape Concern, and Weight Concern. The user guide with information on calculating the subscales is found in Fairburn et al. Eating Disorder Exam.17th ed.; 2014. [222] “Food Craving Inventory” or “FCI” is a self-reported measure of specific food cravings, which measures specific food cravings using two subscales: (1) subjective cravings; and (2) consumption of particular foods. The first subscale (subjective) assessed the frequency of subjective cravings for 47 different foods. The second subscale (behavioral) was intended to measure the extent to which participants gave in to craved foods ( see, e.g ., White et al. Obes Res.2002;10(2):107-114). [223] “Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating” or “Y-BOCS-BE” was developed to assess binge eating related obsessions and compulsions, that is, obsessiveness of binge eating thoughts or urges and compulsiveness of binge eating behaviors. The content of the questions comprising the subscales (e.g., Obsessions and Compulsions) and the total score is the same as that of the original Y-BOCS designed to assess obsessive compulsive symptoms in subjects with OCD, but modified to specifically assess binge eating related obsessions and compulsions ( see, e.g. , Goodman et al. Archives Gen Psych .1989;46(11):1006-1011). [224] “Food Craving Questionnaire” or “FCQ” refers to the self-reported questionnaires designed to assess several aspects relating to food cravings, including any emotions present before a food craving is experienced or before eating, affective responses after eating, thoughts about food, or loss of control over food consumption. FCQs include two versions, namely a “state” questionnaire (FCQ-S) and a “trait” questionnaire (FCQ-T). The FCQ-T reflects 9 subscales, namely: (1) having intentions and plans to consume food; (2) anticipation of positive reinforcement that may result from eating; (3) anticipation of relief from negative states and feelings as a result of eating; (4) lack of control over eating; (5) thoughts and preoccupation with food; (6) craving as a physiological state; (7) emotions that may be experienced before or during food cravings or eating; (8) cues that may trigger food cravings; and (9) guilt from cravings and/or for giving into them ( see, e.g. , Meule et al. Front Psychol .2014;5:190). T he FCQ-S reflects five subscales, namely: (1) an intense desire to eat; (2) anticipation of positive reinforcement that may result from eating; (3) anticipation of relief from negative states and feelings as a result of eating; (4) obsessive preoccupation with 2023-12-14 food or lack of control over eating; and (5) craving as a physiological state ( see, e.g. , Nijs et al. Appetite . 2007;49(1):38-46 ). The term “Food Cravings Questionnaire” includes both the “FCQ-T” and “FCQ-S.” The term “Food Cravings Questionnaire” can be used interchangeably with “Food Urges Questionnaire.” [225] “Three-Factor Eating Questionnaire” or “TFRQ-R18” is a self-reported measure developed to define the relationship between eating behavior and reported food intake. The TFEQ-R18 measures 3 aspects of eating behavior: cognitive restraint (CR), uncontrolled eating (UE), and emotional eating ( see, e.g. , de Lauzon et al. J. Nutr.2004;134(9):2372-2380). [226] “Relationship Patterns Questionnaire” or “RPQ” is a self-reported measure developed to assess the relationship patterns concerning the subject's own behavior as well as the anticipated behavior of an important reference person ( e.g. , Kurth et al. Psychother Psychosom Med Psychol .2005;55(12):502-11). [227] “Treatment Adherence Perception Questionnaire” or “TAPQ” refers to a self-report instrument for assessing patient perceptions and attitudes regarding their own adherence to medical treatment plans. It includes 3 distinct scales: Perceived Behavior, Perceived Benefit, and Perceived Burden ( see, e.g. , Sanford et al. Psychol Assess .2020 Mar;32(3):227-238). [228] “Reward Deficiency Syndrome Questionnaire” or “RDSQ-29” refers to an instrument developed to assess the psychological aspects of “reward deficiency syndrome”, which integrates psychological, neurological, and genetic factors of addictive, impulsive, and compulsive behaviors. The RDSQ-29 has four subscales, namely: (1) lack of sexual satisfaction; (2) activity; (3) social concerns; and (4) risk-seeking behavior ( see, e.g. , Blum et al. Med Res Arch.2023;11(8):10). [229] “Genetic Addiction Risk Severity Test” or “GARS Test” refers to an instrument developed to predict vulnerability to pain, addiction, and other compulsive behaviors in a subject based on ten reward candidate genes that reflected a hypodopaminergic trait, including the dopamine receptors (DRD1, 2, 3, 4); Dopamine Transporter (DAT1); serotonin transporter, COMT, MAO, GABA, Mu opiate receptor, Single Nucleotide Polymorphisms (SNPs), and point mutations ( see, e.g. , Blum et al. Psychol Res Behav Manag . 2023;16:4287-4291). [230] “Civilian Mississippi Post-Traumatic Stress Disorder (PTSD) Scale” or “Civilian M-PTSD Scale” refers to an instrument developed to measure severity of PTSD symptoms. Items are rated on a 5-point Likert scale and summed to yield a continuous measure of PTSD symptom severity ( see, e.g. , Green et al. J Behav Addict.2017;6(1):98-101; [231] “Clinician-Administered PTSD Scale” or “CAPS” refers to an instrument developed to assess post-traumatic stress disorder status and symptom severity ( see, e.g. , Elman et al. Biol Psychiatry. 2009;66(12):1083-1090; Hopper et al. J of Psychiatric Research.2008;42(10):802-807; Elman et al. Front Neurosci.2020;14:604867; Elman et al. Transl Psychiatry.2018;8:240). [232] In embodiments where the psychological factor is health anxiety, improvements in the psychological factor may be evaluated using the STAI or the HAM-A. 2023-12-14 [233] In embodiments where the psychological factor is an impaired quality of life, improvements in the psychological factor may be evaluated using the BDI, the HAM-D, the HAM-A, the STAI, the DSI, the PSS-10, the POMS questionnaire, the YFAS, the EDE-Q, the FCI, the Yale-Brown Obsessive-Compulsive Scale, the FCQs, the TFRQ-R18, the RPQ , the TAPQ , the RDSQ-29, the GARS Test, the CAPS , or the Civilian M-PTSD Scale . [234] In embodiments where the psychological factor is thanatophobia, improvements in the psychological factor may be evaluated using the STAI, the HAM-A, the DSI, or the PSS-10. [235] In embodiments where the psychological factor is disease phobia, improvements in psychological factor may be evaluated using the STAI, the HAM-A, the DSI, or the PSS-10. [236] In embodiments where the psychological factor is illness denial, improvements in the psychological factor may be evaluated using the Cornell Medical Index, Birchwood Insight Scale, the STAI, the HAM-A, the DSI, the PSS-10, the TAPQ , or the Yale-Brown Obsessive-Compulsive Scale. [237] In embodiments where the psychological factor is persistent somatization, improvements in the psychological factor may be evaluated using the Somatic Symptom Scale, the STAI, the HAM-A, the DSI, or the PSS-10. [238] In embodiments where the psychological factor is conversion, improvements in the psychological factor may be evaluated using the AMDP scale for dissociation and conversion, the State Trait Anxiety Inventory, the HAM-A, the DSI, or the PSS-10. [239] In embodiments where the psychological factor is a functional somatic symptom secondary to a psychiatric disorder, improvements in the psychological factor may be evaluated using the BDI, the HAM-D, the HAM-A, the STAI, the DSI, the PSS-10, the POMS questionnaire, the YFAS, the EDE-Q, the FCI, the Yale-Brown Obsessive-Compulsive Scale, the FCQs, the TFRQ-R18, the RPQ , the TAPQ , the RDSQ-29, the GARS Test , the CAPS , the Cornell Medical Index, the Civilian M-PTSD Scale , the Visual Analogue Scale (VAS) for pain, the Numerical Rating Scale (NRS), the Verbal Rating Scale (VRS), or the Faces Pain Scale-Revised (FPS-R). [240] In embodiments where the psychological factor is an anniversary reaction, improvements in the psychological factor may be evaluated using the CAPS , or the Civilian M-PTSD Scale . [241] In embodiments where the psychological factor is demoralization, improvements in the psychological factor may be evaluated using the Demoralization Scale (DS-II), BDI, or the HAM-D. [242] In embodiments where the psychological factor is an irritable mood, improvements in the psychological factor may be evaluated using the the Affective Reactivity Index, the Brief Irritability Test (BITe), or POMS questionnaire. [243] In embodiments where the psychological factor is type A behavior, improvements in the psychological factor may be evaluated using the 24-item Multidimensional Type A Behaviour Scale. [244] In embodiments where the psychological factor is alexithymia, improvements in the psychological 2023-12-14 factor may be evaluated using the Toronto Alexithymia Scale, the CAPS , or the Civilian M-PTSD Scale . [245] In embodiments where the psychological factor is a stressful life event, improvements in the psychological factor may be evaluated using the CAPS , the DSI, or the PSS-10. [246] In embodiments where the psychological factor is depression, improvements in the psychological factor may be evaluated using the BDI or the HAM-D. [247] In embodiments where the psychological factor is general anxiety, improvements in the psychological factor may be evaluated using the STAI or the HAM-A. [248] In embodiments where the psychological factor is anger, improvements in the psychological factor may be evaluated using the Anger Management Scale or the POMS questionnaire. [249] In embodiments where the psychological factor is hostility, improvements in the psychological factor may be evaluated using the State Hostility Scale (SHOS) or the POMS questionnaire. [250] In embodiments where the psychological factor is a maladaptive health behavior, improvements in the psychological factor may be evaluated using the TAPQ . [251] In embodiments where the psychological factor is hypochondriasis, improvements in the psychological factor may be evaluated using the Health Anxiety Inventory (HAI) or STAI, the DSI, or the PSS-10. 2. Methods for Evaluating Improvement Related to IRARD [252] In embodiments, improvements related to IRARD may be improvements in hyperglycemic condition. In embodiments, improvements in hyperglycemic condition may be monitored using a physiological measure. In embodiments, improvements in hyperglycemic condition are monitored using a PCOM. In embodiments, improvements in hyperglycemic condition are monitored using a behavioral factor measure. In embodiments, improvements in hyperglycemic condition are monitored based on measures of glucoregulatory function. [253] In embodiments, glucoregulatory function may be monitored using a primary outcome measure or a secondary outcome measure (although as noted above, such terms are merely suggestive and non-limiting). [254] In embodiments, glucoregulatory function may be monitored using a primary outcome measure. In embodiments, the primary outcome measure is fasting plasma glucose (FPG) concentrations. “Fasting plasma glucose” may refer to the amount of glucose in the blood during a fasted state. In some embodiments, the subject’s glucose levels are compared to their baseline glucose levels, for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s glucose levels remain within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline glucose levels . [255] “Normal” function refers to a fasting plasma glucose (FPG) of less than 100 mg/dL. Prediabetes is diagnosed at a FPG of between 100-125 mg/dL. Diabetes is diagnosed at a FPG of greater than 125 mg/dL. [256] In embodiments, the primary outcome measure is data from a homeostatic model assessment for insulin resistance (HOMA-IR). “Homeostatic model assessment” or “HOMA” refers to a method for assessing 2023-12-14 β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations (Taveira et al. J Psychopharmacol. 2014;28(4):395-400). HOMA-IR estimates insulin resistance, or its inverse, insulin sensitivity (S _i ), from basal measurements of plasma insulin and glucose. Optimally, S _i is determined from a nomogram, but an approximation is often used: S _i = 22.5/I x G , where I and G are fasting insulin and glucose levels, that may be averaged over three measures at different timepoints to adjust for pulsatile secretion (Raziuk, Diabetes.2014;63(6):1850–1854). [257] In embodiments, the primary outcome measure is data collected using the Matsuda Index at 16 weeks following use of a disclosed method. “Matsuda index” refers to a measure of overall insulin sensitivity via simultaneous sampling of plasma insulin and glucose levels during an oral glucose tolerance test (oGTT) at five timepoints (e.g., 0, 30, 60, 90 and 120 min) following glucose ingestion ( see , e.g., Guina et al. Hum. Psychopharmacol.2017; and Guina et al. J Clin Psych.2016). “Oral glucose tolerance test” or “oGTT” refers to a test that measures blood glucose levels before and at a certain point in time after a subject has consumed a glucose-enriched beverage. The test is informative on how the subject processes sugar (Elman et al. Sci Rep.2020; 10(1):5617; Guina et al. J Clin Psych , 2016; 77(12):e1650-e1651). [258] “Normal” blood sugar may refer to a plasma glucose concentration following oGTT of less than 140 mg/dL. Prediabetes is diagnosed at a plasma glucose concentration following oGTT of between 140-199 mg/dL. Diabetes is diagnosed at a plasma glucose concentration following oGTT of greater than 200 mg/dL. [259] In embodiments, the primary outcome measure is the change in a subject’s insulin resistance. In some embodiments, the subject’s insulin resistance is compared to their baseline insulin resistance (e.g., the subject’s insulin resistance when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s insulin resistance remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline insulin resistance. [260] In embodiments, the primary outcome measure is the change in a subject’s hemoglobin A1c (HbA1c) levels. “H emoglobin A1c test” (“HbA1c test”) may refer to a blood test that measures the average blood sugar level of a subject over the past 3 months. The subject is not required to fast or consume glucose to participate in the test. “Normal” A1C is a result of less than 5.7%. Prediabetes is diagnosed at an A1C of 5.7-6.4%. Diabetes is diagnosed at an A1C of greater than or equal to 6.5%. [261] In some embodiments, the subject’s HbA1c is compared to their baseline HbA1c (i.e., the subject’s HbA1c when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s HbA1c remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline HbA1c . [262] In embodiments, glucoregulatory function may be monitored using a secondary outcome measure. In embodiments, the secondary outcome measure is BMI. “Body mass index,” or “BMI,” may refer to a weight 2023-12-14 to height ratio measurement that can be used to estimate whether a subject’s weight is appropriate for their height. A subject’s body mass index can be calculated as a person’s weight in kilograms (or pounds) divided by the square of height in meters (or feet). BMI does not directly measure body fat, but it can be a useful and inexpensive screening method for clinical purposes. For adults, BMI may be categorized into four ranges and indicates varying levels of health risks: < 18.5 kg/m ² indicates underweight; 18.5-24.9 kg/m ² indicates a normal/healthy state; 25-29.9 kg/m ² indicates overweight; and 30 kg/m ² or greater indicates obese. Too little or too much body fat (as compared to a BMI in normal range) reflects a risk of disease predisposition. In embodiments, the subject’s BMI is compared to their baseline BMI (e.g., the BMI when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s BMI remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline BMI . Preferably, their BMI remains within 1%, 5%, or 10% of their baseline BMI . [263] In embodiments, the secondary outcome measure is body fat and fat-free mass. “Body fat mass” (FM) may refer to the weight of fat in a human body. The term “fat-free mass” refers exclusively to the composite materials that make up the human body and which do not contain fat deposits, such as vital organs, bones, connective tissue, and water. [264] In embodiments, FM and fat-free mass may be determined in a subject using a bioelectrical impedance analysis or a dual x-ray absorptiometry (DEXA) scan with low-level x-rays ( see, e.g ., Taveira et al. J. Psychopharmacol.2014;28(4):395-400; and Elman et al. Sci Rep.2020;10(1):5617). A “bioelectrical impedance analysis” may refer to a measure of body composition based on the rate at which an electrical current travels through the body. Body fat (adipose tissue) causes greater resistance (impedance) than lean mass and slows the rate at which the current travels. A “dual x-ray absorptiometry scan” or a “DEXA scan” may refer to a test that uses imaging technology to measure whole body composition. [265] In embodiments, the subject’s FM and fat-free mass are compared to their baseline FM and fat-free mass (e.g., the subject’s FM and fat-free mass when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s FM and fat-free mass remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline FM and fat-free mass . [266] In embodiments, the secondary outcome measure is data collected from a lipid test. “Lipid test” may refer to a test which measures the amount of cholesterol and triglycerides present in a subject’s blood. In embodiments, lipid tests include monitoring for total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. Cholesterol are fats that are in the blood. LDL cholesterol is considered unhealthy cholesterol, and HDL cholesterol is considered healthy cholesterol because it helps the body get rid of excess cholesterol. Lipid test results are given in milligrams per deciliter (mg/dL). Adults with 2023-12-14 normal levels of cholesterol will show a lipid test result of less than about 200 mg/dL. Adults with borderline high levels of cholesterol will show a lipid test result of between about 200 to 239 mg/dL. Adults with high levels of cholesterol will show a lipid test result at or above about 240 mg/dL. In embodiments, the subject’s lipid levels are compared to their baseline lipid levels (i.e., the subject’s lipid levels when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s lipid levels remain within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline lipid levels . [267] In embodiments, the secondary outcome measure is data collected from a liver function test. “Liver function test” may refer to a blood test which measures liver function. Liver function tests measure levels of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Liver function tests also measure serum bilirubin, prothrombin time (PT), international normalized ratio (INR), and total protein and albumin levels. Liver function tests may be used to determine areas of the liver where damage may be taking place and, depending on patterns of elevation, can help ensure a proper diagnosis for a subject. For example, elevations in ALT and AST that are disproportionate to elevations in ALP and bilirubin may denote hepatocellular disease. An elevation in ALP and bilirubin in disproportion to ALT and AST would characterize a cholestatic pattern. [268] In embodiments, the secondary outcome measure is the change in the subject’s body weight. In some embodiments, the subject’s body weight is compared to their baseline weight (i.e., the subject’s weight when the subject was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject maintains their baseline weight. In embodiments, maintaining baseline weight is defined as the subject’s weight remaining within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline weight. In embodiments, the subject regains less than 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or 65% of the weight they lost during treatment. [269] In embodiments, the secondary outcome measure is the change in the subject’s average adipocyte diameter . Studies show that adipocyte diameter is related to insulin resistance, type 2 diabetes, and diet interventions (Stenkula & Erlanson-Albertsson. Am J Physiol Regul Integr Comp Physiol .2018;315(2):284- 295). Adipocyte diameter can be measured according to standard techniques known to those of skill. In embodiments, the subject’s average adipocyte diameter is compared to their baseline average adipocyte diameter (i.e., the subject’s average adipocyte diameter when he or she was diagnosed with hyperglycemia) for a period of time after commencement of treatment for hyperglycemia (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s average adipocyte diameter remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline adipocyte 2023-12-14 diameter . In embodiments, the subject’s average adipocyte diameter remains within 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, or 10 μm of their baseline adipocyte diameter. [270] Other methods for evaluating improvements related to IRARD, useful in the practice of the disclosed methods, will be known to those of skill in view of the teachings herein and the general knowledge in the art. 3. Methods for Evaluating Improvement Related to Hypertension [271] In embodiments, improvements related to hypertension may be improvements in hypertension. In embodiments, improvements in hypertension may be monitored using a physiological measure. In embodiments, improvements in hypertension may be monitored using a patient-centered outcome measure. In embodiments, improvements in hypertension may be monitored using a behavioral factor measure. In embodiments, improvements in hypertension are monitored based on measures of blood pressure. [272] One of skill can monitor improvements in hypertension in a subject by observing statistically significant changes in systolic and diastolic blood pressure. Upon commencement of treatment for hypertension, it would be expected that the subject would begin to exhibit a stabilized blood pressure, with systolic and diastolic values of less than 140/90 mm Hg, respectively. [273] In some embodiments, the result of a disclosed method is assessed by measuring a change in the subject’s systolic blood pressure. In some embodiments, the subject’s systolic blood pressure is compared to their baseline systolic blood pressure (e.g., the subject’s systolic blood pressure when the subject was diagnosed with hypertension) for a period of time after commencement of treatment for hypertension (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s systolic blood pressure remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline systolic blood pressure . [274] In some embodiments, the result of a disclosed method is assessed by measuring a change in the subject’s diastolic blood pressure. In some embodiments, the subject’s diastolic blood pressure is compared to their baseline diastolic blood pressure (e.g., the subject’s diastolic blood pressure when the subject was diagnosed with hypertension) for a period of time after commencement of treatment for hypertension (e.g., 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, or longer than 12 months). In embodiments, the subject’s diastolic blood pressure remains within 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% of their baseline diastolic blood pressure . [275] Other methods for evaluating improvements related to hypertension, useful in the practice of the disclosed methods, will be known to those of skill in view of these teachings and the knowledge in the art. 4. Methods for Evaluating Improvement Related to Inflammatory Disorders [276] In embodiments, improvements related to an inflammatory disorder may be improvements in an inflammatory response. In embodiments, improvements in an inflammatory response may be monitored using a physiological measure. In embodiments, improvements in an inflammatory response may be monitored using a patient-centered outcome measure. In embodiments, improvements in an inflammatory 2023-12-14 response may be monitored using a behavioral factor measure. [277] One of skill can monitor improvements in an inflammatory response by using one or more types of laboratory analyses to detect inflammatory biomarkers in a subject. [278] In embodiments, improvements in an inflammatory response may be monitored using a C-reactive protein test. “C-reactive protein” or “CRP” may refer to an annular (ring-shaped) pentameric protein found in blood plasma. A CRP test measures the level of CRP in a subject’s blood. The liver releases CRP into the bloodstream in response to inflammation. Traditional CRP tests only detect CRP in amounts ranging from between about 10 to 1,000 mg/L, whereas high sensitivity CRP tests (hs-CRPs) detect CRP in amounts ranging from between about 0.5 to 10 mg/L. [279] In embodiments, improvements in an inflammatory response may be monitored by determining the erythrocyte sedimentation rate (ESR) in a subject. “Erythrocyte sedimentation rate” (ESR) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. An ESR test is common in hematology, and is a non-specific measure of inflammation. To perform an ESR test, anticoagulated blood is placed in an upright tube, known as a Westergren tube, and the distance at which the red blood cells fall is measured and reported in millimeters at the end of one hour. In inflammatory disorders, fibrinogen, other clotting proteins, and alpha globulin are positively charged, thus increasing the ESR. For example, the ESR typically begins to rise at 24-48 hours after the onset of acute self-limited inflammation, decreases slowly as inflammation resolves, and can take weeks to months to return to normal levels. [280] In embodiments, improvements in an inflammatory response may be monitored using a plasma viscosity test. Plasma viscosity can serve as a marker of inflammation in a subject. Plasma viscosity (PV) measures the viscosity, or the 'thickness' of a subject’s plasma, and is affected by the amount of proteins in the blood. Protein levels in the blood can increase as part of a normal response to infection or inflammation. Normal levels of plasma viscosity in a subject are between about 1.3-1.7mPas (millipascal second). The higher the plasma viscosity in a subject, the more viscous the blood, which in turn signals the presence of a more severe inflammatory response. [281] In embodiments, improvements in an inflammatory response may be monitored by analyzing procalcitonin levels in a subject. Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. PCT arises once pre-procalcitonin is cleaved by endopeptidase. The level of procalcitonin in the blood stream of healthy subjects is below the limit of detection (0.01 µg/L) of clinical assays (Schuetz et al. BMC Medicine.2011;9:107). However, levels of procalcitonin in the blood may be elevated in a number of different inflammatory disorders. [282] In embodiments, improvements in an inflammatory response may be monitored by analyzing ferritin levels in a subject. Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. Ferritin serves as a biomarker of inflammation in subjects. For men, a normal range for ferritin levels in the blood is between about 24 to 336 micrograms per liter. For women, a normal range for ferritin levels in 2023-12-14 the blood is between about 11 to 307 micrograms per liter. Higher levels of ferritin in the blood indicate the presence of one or more inflammatory disorders in a subject (Khan et al. J. Obes.2016;2016:1937320). [283] In embodiments, improvements in an inflammatory response may be monitored by analyzing fibrinogen levels in a subject. Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. Fibrinogen is a "positive" acute-phase protein, meaning its blood levels rise in response to systemic inflammation, tissue injury, and certain other events. Elevated levels of fibrinogen in the blood due to inflammation as well as cancer or other conditions have been suggested to be the cause of thrombosis and vascular injury. Normal levels of fibrinogen in a subject are between about 1.5-3 g/L (Alexander et al. Thromb Haemost.2011;105(4):605-9). [284] Other methods for evaluating improvements related to inflammatory disorders, useful in the practice of the disclosure, will be known to those of skill in view of these teachings and the knowledge in the art. 5. Methods for Evaluating Improvement in Additional Other Medical Conditions [285] In embodiments, improvements in additional other medical conditions, i.e., beyond those above, may be evaluated using a physiological measure. In embodiments, improvements in other medical conditions may be evaluated using a patient-centered outcome measure. In embodiments, improvements in other medical conditions may be evaluated using a behavioral factor measure. [286] In embodiments, improvements in such other medical conditions are evaluated using techniques and measures known to those of skill in the art. As non-limiting and merely suggestive examples: [287] In embodiments, improvements in a sleep disorder may be determined using a polysomnogram (PSG). In embodiments, improvements in a sleep disorder may be determined using a multiple sleep latency test (MSLT). In embodiments, improvements in a sleep disorder may be determined using a continuous positive airway pressure (CPAP) titration. In embodiments, improvements in a sleep disorder may be determined using a split night study. In embodiments, improvements in a sleep disorder may be determined using a maintenance of wakefulness test (MWT). In embodiments, improvements in a sleep disorder may be determined using the Pittsburgh Quality Sleep Index (PSQI). [288] In embodiments, improvements in a musculoskeletal condition may be determined using the Musculoskeletal Health Questionnaire (MSK-HQ). In embodiments, improvements in a musculoskeletal condition may be monitored by determining the erythrocyte sedimentation rate (ESR) in a subject. In embodiments, improvements in a musculoskeletal condition may be determined using an x-ray. In embodiments, improvements in a musculoskeletal condition may be determined using a bone scan. In embodiments, improvements in a musculoskeletal condition may be determined using computed tomography (CT). In embodiments, improvements in a musculoskeletal condition may be determined using a magnetic resonance imaging (MRI). [289] In embodiments, improvements in a renal disorder may be determined based on measures of blood pressure. In embodiments, improvements in a renal disorder may be determined based on a subject’s blood 2023-12-14 glucose levels. In embodiments, improvements in a renal disorder may be determined using a glomerular filtration rate (GFR) test. [290] In embodiments, improvements in a hematological disorder may be determined using a test which monitors complete blood cell count in a subject. In embodiments, improvements in a hematological disorder may be determined using a test which monitors platelet count in a subject. In embodiments, improvements in a hematological disorder may be determined using blood enzyme tests. In embodiments, improvements in a hematological disorder may be determined using a bone marrow biopsy. [291] In embodiments, improvements in a neurodegenerative disorder may be determined using the Parkinson’s Disease Questionnaire (PDQ-39). In embodiments, improvements in a neurodegenerative disorder may be determined using the Multiple Sclerosis Impact Scale (MSIS-29). In embodiments, improvements in a neurodegenerative disorder may be determined using the 36-item Short Form Health Survey (SF-36). In embodiments, improvements in a neurodegenerative disorder may be determined using the EQ-5D. [292] In embodiments, improvements in any other medical condition may be determined using the assessment of the quality of life (QOL). [293] Other measures of improvements in disclosed medical conditions will be known to those of skill. III. Pharmaceutical Agents [294] In some aspects are disclosed methods of treating a subject with one or more pharmaceutical agents, pharmaceutical compositions comprising such agents, and kits comprising such agents. “Compound” also may be used equivalently herein to refer to an “agent.” [295] Although agents are categorized herein by class, and generally attributed to a single class, it will be appreciated that any classification is not exclusive, and any agent may belong to more than one class. Classification of agents herein is for reference only, and other classifications will be known to those of skill. [296] Disclosure of any agent herein must be understood to encompass and refer to the pharmaceutically acceptable salts, stereoisomers, polymorphs, hydrates, solvates, isotopic derivatives, and prodrugs thereof. [297] “Pharmaceutically acceptable salt” refers to the salts prepared from pharmaceutically acceptable non-toxic acids or bases, and which may be synthesized by conventional chemical methods. Generally, such salts are prepared by reacting the free acid or base forms of these agents with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media (e.g., ether, ethyl acetate, ethanol, isopropanol, or acetonitrile) are preferred. For therapeutic use, salts of the agents are those wherein the counter-ion is pharmaceutically acceptable. One of skill can select from among a wide variety of available counterions those that are pharmaceutically acceptable. In specific applications, the selection of a given anion or cation for preparation of a salt may result in increased or decreased solubility of that salt. Exemplary salts include 2-hydroxyethanesulfonate, 2-naphthalenesulfonate, 2-napsylate, 3-hydroxy-2-naphthoate, 3-phenyl- propionate, 4-acetamidobenzoate, acefyllinate, acetate, 2023-12-14 aceturate, adipate, alginate, aminosalicylate, ammonium, amsonate, ascorbate, aspartate, benzenesulfonate, benzoate, besylate, bicarbonate, bisulfate, bitartrate, borate, butyrate, calcium edetate, calcium, camphocarbonate, camphorate, camphorsulfonate, camsylate, carbonate, cholate, citrate, clavulariate, cyclopentanepropionate, cypionate, d-aspartate, d-camsylate, d-lactate, decanoate, dichloroacetate, digluconate, dodecylsulfate, edentate, edetate, edisylate, estolate, esylate, ethanesulfonate, ethyl sulfate, fumarate, furate, fusidate, galactarate (mucate), galacturonate, gallate, gentisate, gluceptate, glucoheptanoate, gluconate, glucuronate, glutamate, glutarate, glycerophosphate, glycolate, glycollylarsanilate, hemisulfate, heptanoate (enanthate), heptanoate, hexafluorophosphate, hexanoate, hexylresorcinate, hippurate, hybenzate, hydrabamine, hydrobromide, hydrobromide/bromide, hydrochloride, hydroiodide, hydroxide, hydroxybenzoate, hydroxynaphthoate, iodide, isethionate, isothionate, l-aspartate, l-camsylate, l-lactate, lactate, lactobionate, laurate, laurylsulphonate, lithium, magnesium, malate, maleate, malonate, mandelate, meso-tartrate, mesylate, methanesulfonate, methylbromide, methylnitrate, methylsulfate, mucate, myristate, N-methylglucamine ammonium salt, napadisilate, naphthylate, napsylate, nicotinate, nitrate, octanoate, oleate, orotate, oxalate, p-toluenesulfonate, palmitate, pamoate, pantothenate, pectinate, persulfate, phenylpropionate, phosphate, phosphateldiphosphate, picrate, pivalate, polygalacturonate, potassium, propionate, pyrophosphate, saccharate, salicylate, salicylsulfate, sodium, stearate, subacetate, succinate, sulfate, sulfosaliculate, sulfosalicylate, suramate, tannate, tartrate, teoclate, terephthalate, thiocyanate, thiosalicylate, tosylate, tribrophenate, triethiodide, undecanoate, undecylenate, valerate, valproate, xinafoate, zinc, and the like ( see, e.g ., Berge, et al., J. Pharm. Sci .1997;66:1-19). [298] A disclosed pharmaceutical agent can exist in solid or liquid form. In the solid state, the compound may exist in crystalline or noncrystalline form, or as a mixture thereof. The skilled artisan will appreciate that pharmaceutically acceptable solvates may be formed for crystalline or non-crystalline compounds. In crystalline solvates, solvent molecules are incorporated into the crystalline lattice during crystallization. Solvates may involve non-aqueous solvents such as, but not limited to, ethanol, isopropanol, DMSO, acetic acid, ethanolamine, or ethyl acetate, or they may involve water as the solvent that is incorporated into the crystalline lattice. Solvates wherein water is the solvent incorporated into the crystalline lattice are typically referred to as “hydrates.” Hydrates include stoichiometric hydrates as well as compositions containing variable amounts of water. The subject matter described herein includes such solvates. [299] One of skill will further appreciate that certain pharmaceutical agents described herein that exist in crystalline form, including the various solvates thereof, may exhibit polymorphism (i.e. the capacity to occur in different crystalline structures). These different crystalline forms are typically known as “polymorphs.” The subject matter disclosed herein includes such polymorphs. Polymorphs include the different crystal packing arrangements of the same elemental composition of an agent. Polymorphs have the same chemical composition but differ in packing, geometrical arrangement, and other descriptive properties of the crystalline solid state. Polymorphs, therefore, may have different physical properties such as shape, density, hardness, 2023-12-14 deformability, stability, and dissolution properties. Polymorphs typically exhibit different melting points, IR spectra, and X-ray powder diffraction patterns, which may be used for identification. The skilled artisan will appreciate that different polymorphs may be produced, e.g., by changing or adjusting the reaction conditions or reagents used in making the compound. For example, changes in temperature, pressure, or solvent may result in polymorphs. Various factors such as the recrystallization solvent, rate of crystallization, and storage temperature may cause a single crystal form to dominate. One polymorph also may spontaneously convert to another polymorph under certain conditions. [300] Disclosed pharmaceutical agents may contain one or more asymmetric centers and give rise to enantiomers, diastereomers, and other stereoisomeric forms. Each chiral center may be defined, in terms of absolute stereochemistry, as (R)– or (S)–. The invention includes all such possible isomers, as well as mixtures thereof, including racemic and optically pure forms. Optically active (R)– and (S)–, (–)– and (+)–, or (D)– and (L)–isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. Various methods are known in the art for preparing optically active forms and determining activity. Such methods include standard tests described herein and other similar tests which are well known in the art. Examples of methods that can be used to obtain optical isomers of the compounds according to the present disclosure include selective crystallization, enzymatic resolution, asymmetric synthesis (including asymmetric chemical synthesis and asymmetric enzymatic synthesis), kinetic resolution, and chiral chromatography (including chiral liquid chromatography, gas chromatography, and high-performance liquid chromatography). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. Likewise, tautomeric forms are included. [301] When the pharmaceutical agents described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. Likewise, tautomeric forms are included. [302] The disclosure also includes pharmaceutical agents with at least one desired isotopic substitution of an atom, at an amount above the natural abundance of the isotope, i.e., isotopically enriched. Isotopes are atoms having the same atomic number but different mass numbers, i.e., the same number of protons but a different number of neutrons. Examples of isotopes that can be incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, and chlorine such as 2H, 3H, 11C, 13C, 14C, 15N, 17O, 18O, and 36Cl respectively. In one non-limiting embodiment, isotopically labeled compounds can be used in metabolic studies (with 14C), reaction kinetic studies (with, for example 2H or 3H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in radioactive treatment of patients. In particular, an 18F-labeled compound may be particularly desirable for PET or SPECT studies. Further, substitution with heavier isotopes such as deuterium, i.e., 2H, can afford certain therapeutic 2023-12-14 advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of this invention can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. [303] The disclosure of an agent also includes its prodrugs. A “prodrug” is a precursor of a biologically active pharmaceutical agent, which may undergo a chemical or a metabolic conversion to become the biologically active agent. A prodrug can be converted ex vivo to the biologically active pharmaceutical agent by chemical transformative processes. In vivo, a prodrug is converted to the biologically active pharmaceutical agent by the action of a metabolic process, an enzymatic process, or a degradative process that removes the prodrug moiety to form the biologically active pharmaceutical agent. Typical examples of prodrugs include compounds with biologically labile or cleavable (protecting) groups on a functional moiety of the active compound. Prodrugs include compounds that can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, alkylated, dealkylated, acylated, deacylated, phosphorylated, or dephosphorylated to produce the active compound. Commonly used functional groups include esters, carbonates, carbamates, amides, phosphates, and sulfonamides. These functional groups can be attached to the drug molecule via a linker that is designed to be cleaved under specific physiological conditions, such as enzymatic hydrolysis or pH-dependent cleavage. The choice of functional group depends on factors such as stability, ease of synthesis, enzymatic activity, and desired rate of prodrug conversion. [304] Generally, the individual disclosed pharmaceutical agents will be administered as part of a pharmaceutical composition or formulation, and are prepared for inclusion in such composition or formulations as isolated or purified compounds. The terms “isolated,” “purified,” or “substantially pure,” as used herein, refer to material that is substantially or essentially free from components that normally accompany the material when the material is synthesized, manufactured, or otherwise produced. [305] An “isolated,” “purified,” or “substantially pure” preparation of an agent is accordingly defined as a preparation having a chromatographic purity (of the desired compound) of greater than 90%, more preferably greater than 95%, more preferably greater than 96%, more preferably greater than 97%, more preferably greater than 98%, more preferably greater than 99%, more preferably greater than 99.5%, and most preferably greater than 99.9%, as determined by area normalization of an HPLC profile or other similar detection method. Preferably the substantially pure compound used in the disclosure is substantially free of any other active compounds which are not intended to be administered to a subject. In this context “substantially free” can be taken to mean that no active compound(s) other than the active compound intended to be administered to a subject are detectable by HPLC or other similar detection method, or are below a desired threshold of detection such as defined above. 2023-12-14 A. First Agents: Monoamine Oxidase A Inhibitors [306] In some aspects, disclosed methods comprise administering a first pharmaceutical agent and, optionally, a second pharmaceutical agent. In some aspects, a disclosed pharmaceutical composition or kit comprises a first pharmaceutical agent and, optionally, a second pharmaceutical agent. In embodiments, the first pharmaceutical agent (as shorthand herein, “first agent”) is an MAOI, which may be, e.g., a selective inhibitor such as a MAO-A-selective inhibitor, or a reversible inhibitor of monoamine oxidase A (RIMA). [307] Monoamine oxidase (MAO) is a widely distributed mitochondrial enzyme expressed in gastrointestinal, hepatic, and neuronal tissue. A primary function of MAO enzymes is the oxidative deamination of endogenous and exogenous monoamines, which renders them physiologically inert. This process detoxifies potentially harmful monoamines in the diet, and recycles/prevents the buildup of neurotransmitters in nervous and other tissues (Finberg et al. Front Pharmacol .2016;7:340). There are two MAO isoforms: MAO-A and MAO-B. Where as both isoforms have a similar affinity for dopamine (DA) and tyramine, MAO-A has a greater affinity for hydroxylated amines such as serotonin (5-hydroxytryptamine, 5-HT), and noradrenaline (NA) while MAO-B has greater affinity for non-hydroxylated amines such as benzylamine and beta-phenylethylamine (PEA). Due to their regulation of neurotransmitter levels, alterations in MAO activity is thought to underlie some neurological and psychiatric disorders, and have thus been a target of treatment for several decades. Research suggests that monoaminergic neurotransmission may be enhanced by inhibiting MAO-A ( see, e.g. , Chen et al. Pol J Pharmaco l.1999;51(1):25-9). [308] “MAO inhibitor” or “MAOI” may refer to any compound, whether natural or synthetic, that exhibits the ability to inhibit the enzymatic activity of MAO, including MAO-A and MAO-B. It encompasses all chemical structures, including organic molecules, peptides, proteins, nucleic acids, derivatives, analogs, and combinations thereof, capable of interfering with the catalytic function of monoamine oxidase enzymes, thereby preventing or reducing the metabolism or breakdown of monoamine neurotransmitters. [309] The term “MAO inhibitor” or “MAOI” further encompasses reversible, irreversible, competitive, non-competitive, selective, and non-selective inhibitors, as well as any substance that indirectly modulates or regulates monoamine oxidase activity through allosteric, regulatory, or indirect mechanisms. [310] “MAO-A-selective inhibitor” may refer to an MAOI that exhibits selectivity for inhibiting monoamine oxidase A (MAO-A) over monoamine oxidase B (MAO-B). For a MAO inhibitor, selectivity can be calculated by comparing the inhibitory constant (K _i ) or half maximal effective concentration (EC ₅₀ ) for MAO-A and MAO-B. For example, if an inhibitor has a K _i of 0.2 μM for MAO-A and a K _i of 1.0 μM for MAO-B, it can be said to have a 5-fold selectivity for MAO-A (i.e., the inhibitor exhibits a 5-fold higher affinity or potency for MAO-A over MAO-B). K _i can be measured according to methods known to those of skill in the art. [311] In some embodiments, the MAOI, or a salt thereof, is a MAO-A-selective inhibitor (i.e., the MAO inhibitor exhibits higher potency for MAO-A over MAO-B; or, in other words, the MAO-inhibitor has a lower K _i for MAO-A inhibition than for MAO-B inhibition). In some embodiments, the MAOI has a selectivity for MAO-A 2023-12-14 inhibition over MAO-B inhibition of at least 5-fold, at least 10-fold, at least 50-fold, at least 100-fold, at least 150-fold, at least 200-fold, at least 300-fold, at least 500-fold, or at least 1,000-fold. In embodiments, the MAOI does not result in a detectable amount of MAO-B inhibition. [312] In some embodiments, the MAOI is any of isocarboxazid, pargyline, selegiline, furazolidone, phenelzine, amiflamine, iproniazid, nialamide, tranylcypromine, octamoxin, phenoxypropazine, pivalyl benzhydrazine, iproclozide, bifemelane, prodipine, benmoxin, etryptamine, fenoxypropazine, mebanazine, pheniprazine, safrazine, hypericine, iproniazid, tranylcypromine, methylene blue, moclobemide, brofaromine, befloxatone, toloxatone, clorgyline, cimoxatone, bazinaprine, harmine, harmaline, sercloremine, esuprone, pirlindole, metralindole, and tetrindole. [313] In some embodiments, the MAOI is an MAO-A-selective inhibitor. In some embodiments, the MAOI is an MAO-B-selective inhibitor. In some embodiments, the MAOI is a non-selective inhibitor. In some embodiments, the MAOI is an irreversible inhibitor. In embodiments, the MAOI is irreversible and selective. In some embodiments, the MAOI is selegiline. In some embodiments, the MAOI is a MAO-B reversible inhibitor. In some embodiments, the MAOI is irreversible and non-selective. In embodiments, the MAOI is phenelzine. In embodiments, the MAOI is tranylcypromine. In embodiments, the MAOI is isocarboxazid. [314] Selective inhibitors of MAO-A can exhibit advantageous properties over non-selective inhibitors. Despite their efficacy in some situations, MAOIs are often contraindicated for patients due to their cardiovascular effects and diet restriction requirements. These issues may be overcome with RIMAs. As serotonin, norepinephrine, and dopamine are primarily metabolized by MAO-A, RIMAs inhibit the breakdown of serotonin, norepinephrine, and dopamine (Fowler et al. Neuropsychopharmacol .2010;35(3):623-631). [315] In some embodiments, the first agent is a RIMA. RIMAs have been used in clinical contexts, especially in an antidepressant capacity (Carradori et al. Expert Opin Ther Pat .2015;25(1):91-110). In embodiments, the MAOI is also an antidepressant. In embodiments, the MAOI is not also an antidepressant. [316] In some embodiments, the MAOI is a MAO-A reversible inhibitor (RIMA). [317] In some embodiments, the RIMA is selected from the group consisting of moclobemide, brofaromine, caroxazone, CX157, CX2614, eprobemide, metralindole, minaprine, pirlindole, or toloxatone. [318] In some embodiments, the RIMA is selected from the group consisting of moclobemide, brofaromine, caroxazone, eprobemide, metralindole, minaprine, or pirlindole. [319] In embodiments, the RIMA is brofaromine. In embodiments, the RIMA is caroxazone. In embodiments, the RIMA is CX157 (i.e., 3-fluoro-7(2,2,2-trifluorethoxy)phenoxathiine-10,10-dioxide). In embodiments, the RIMA is CX2614 (i.e., 3-(2,2,2-trifluoro-1-methylethoxy)phenoxathiin-10,10-dioxide). In embodiments, the RIMA is eprobemide. In embodiments, the RIMA is metralindole. In embodiments, the RIMA is minaprine. In embodiments, the RIMA is pirlindole. In embodiments, the RIMA is toloxatone. [320] In embodiments, the RIMA is moclobemide. [321] As with all disclosed pharmaceutical agents, “moclobemide” refers not only to the drug substance 2023-12-14 4-chloro-N-[2-(morpholin-4-yl)ethyl]benzamide (CAS 71320-77-9) and its salts, but also to all of the drug products comprising moclobemide, e.g., AMIRA® , AURORIX® , CLOBEMIX® , DEPNIL® , and MANERIX® . [322] Thus, in embodiments, moclobemide is AMIRA® , AURORIX® , CLOBEMIX® , DEPNIL® , or MANERIX® . [323] For any disclosed pharmaceutical agent, the agent may be formulated as a pharmaceutical composition, e.g., may be prepared for administration or as a dosage form, including a unit dosage form, and may further comprise one or more carriers, diluents, or excipients, in accordance with the disclosure herein and the general knowledge in the art. Where a disclosed pharmaceutical agent is already known as a component of one or more drug products, while those drug product(s) will not be exclusive of the disclosed pharmaceutical compositions that comprise the pharmaceutical agent, those drug product(s) will be understood to be expressly part of this disclosure, and their product labels, package inserts, medication guides, and associated prescribing information shall be incorporated by reference as if fully set forth herein. B. Second Agents [324] In some aspects, the disclosed methods comprise administering a first pharmaceutical agent and a second pharmaceutical agent. In some aspects, a disclosed pharmaceutical composition or pharmaceutical kit comprises a first pharmaceutical agent and a second pharmaceutical agent. In some embodiments, the second pharmaceutical agent (as shorthand herein, “second agent”) is an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent. [325] In some embodiments, the second pharmaceutical agent is an “additional active agent,” as defined herein. In some embodiments, the disclosed methods comprise administering a first pharmaceutical agent, a second pharmaceutical agent, and an additional active agent. In some embodiments, a disclosed pharmaceutical composition or pharmaceutical kit comprises a first pharmaceutical agent, a second pharmaceutical agent, and an additional active agent. [326] Where a method, composition, or kit of the disclosure comprises more than one pharmaceutical agent, the two or more pharmaceutical agents may be referred to together as a “therapeutic combination.” A therapeutic combination means, for example, that the agents are administered as part of a disclosed method, but is not intended to mean nor should mean that the agents are co-administered simultaneously or together, or the agents have the same preparation or formulation, route of administration, dosing regimen, or the like. 1. Antihyperglycemic Agents [327] In embodiments, the second agent is an antihyperglycemic agent. “Antihyperglycemic agent” may refer to an agent that lowers glucose levels in the blood. For example, biguanides such as metformin decrease glucose production, decrease gastrointestinal glucose absorption, and increase target cell insulin sensitivity. “Insulin sensitivity” may refer to the ability of cells to respond to insulin and take up glucose from the bloodstream. Improved insulin sensitivity enhances monoaminergic neurotransmission, such as by stabilizing dopaminergic function, for example, which can improve a subject’s affective state(s) ( see, e.g. , Wiernsperger et al., Drugs .1999; 58(1 Supp.): 31-39). 2023-12-14 [328] In some embodiments, the antihyperglycemic agent is any of an insulin, a sulfonylurea (e.g., glipizide, glyburide, gliclazide, glimepiride), a meglitinide (e.g., repaglinide and nateglinide), a biguanide (e.g., metformin), a thiazolidinedione (e.g., rosiglitazone, pioglitazone), an ɑ-glucosidase inhibitor (e.g., acarbose, miglitol, voglibose), a DPP-4 inhibitor (e.g., sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin), a SGLT2 inhibitor (e.g., dapagliflozin and canagliflozin), and a dopamine receptor agonist (e.g., bromocriptine). [329] In embodiments, the antihyperglycemic agent is an insulin. Exemplary insulins include insulin glulisine (e.g., APIDRA® ), insulin aspart (e.g., NOVOLOG® ), insulin lispro U-100/U-200 (e.g., HUMALOG® ), regular insulin (e.g., Novolin R, Humulin R), and Neutral Protamine Hagedorn (NPH) insulin (e.g., Novolin N, Humulin N). In embodiments, the antihyperglycemic agent is insulin glulisine. In embodiments, the antihyperglycemic agent is insulin aspart. In embodiments, the antihyperglycemic agent is insulin lispro U-100/U-200. In embodiments, the antihyperglycemic agent is regular insulin. In embodiments, the antihyperglycemic agent is NPH insulin. In embodiments, the antihyperglycemic agent is a sulfonylurea. In embodiments, the antihyperglycemic agent is a meglitinide. In embodiments, the antihyperglycemic agent is a biguanide. In embodiments, the antihyperglycemic agent is a thiazolidinedione. In embodiments, the antihyperglycemic agent is an ɑ-glucosidase inhibitor. In embodiments, the antihyperglycemic agent is a DPP-4 inhibitor. In embodiments, the antihyperglycemic agent is a SGLT2 inhibitor. In embodiments, the antihyperglycemic agent is a dopamine receptor agonist. In embodiments, the antihyperglycemic agent is any of insulin glulisine, insulin aspart, insulin lispro, regular insulin, NPH insulin, glipizide, glyburide, glicla- zide, glimepiride, repaglinide, nateglinide, metformin, rosiglitazone, pioglitazone, acarbose, miglitol, vogli- bose, sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin, dapagliflozin, canagliflozin, and bromocriptine. 2. Antioxidants [330] In embodiments, the second agent is an antioxidant. “Antioxidants” may refer to a class of agents that may prevent or delay cell damage. An antioxidant may work by inhibiting oxidation, or by removing potentially damaging oxidizing agents in a living organism. For example, antioxidants can fight damaging free radicals in an organism which can cause harm if levels become too high. Antioxidants are found in many foods, including fruits and vegetables. Antioxidants are also available as dietary supplements. [331] In embodiments, the antioxidant is any of vitamin C (e.g., ascorbic acid), glutathione, flavonoids, alpha lipoic acid (ALA), Β-carotene, vitamin E (e.g., alpha-tocopherol), ubiquinone, lycopene, coenzyme Q10 (CoQ10), ellagic acid, vitamin A (e.g., retinol), masoprocol, pramipexole, nitric oxide, allopurinol, pentoxifylline, melatonin, probucol, quercetin, acetylcysteine, N-acetylcysteine (NAC), acetyl-L-carnitine, and L-methylfolate. [332] In embodiments, the antioxidant is vitamin C. In embodiments, the antioxidant is ascorbic acid. In embodiments, the antioxidant is glutathione. In embodiments, the antioxidant is flavonoids. In embodiments, the antioxidant is alpha lipoic acid. In embodiments, the antioxidant is Β-carotene. In embodiments, the antioxidant is vitamin E. In embodiments, the antioxidant is alpha-tocopherol. In embodiments, the 2023-12-14 antioxidant is ubiquinone. In embodiments, the antioxidant is lycopene. In embodiments, the antioxidant is coenzyme Q10. In embodiments, the antioxidant is ellagic acid. In embodiments, the antioxidant is vitamin A. In embodiments, the antioxidant is masoprocol. In embodiments, the antioxidant is pramipexole. In embodiments, the antioxidant is nitric oxide. In embodiments, the antioxidant is allopurinol. In embodiments, the antioxidant is pentoxifylline. In embodiments, the antioxidant is melatonin. In embodiments, the antioxidant is probucol. In embodiments, the antioxidant is quercetin. In embodiments, the antioxidant is acetylcysteine. In embodiments, the antioxidant is N-acetylcysteine. In embodiments, the antioxidant is acetyl-L-carnitine. In embodiments, the antioxidant is L-methylfolate. 3. Anti-Inflammatory Agents [333] In embodiments, the second agent is an anti-inflammatory agent. “Anti-inflammatory agent” may refer to agents that can reduce inflammation or swelling, including common non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin. [334] In embodiments, the anti-inflammatory agent is selected from the group consisting of apremilast, prednisone, hydrocortisone, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, mefenamic acid, nabumetone, naproxen, tolmetin, piroxicam, celecoxib, etoricoxib, aspirin, naproxen, meloxicam, apremilast, an anti-cytokine agent (e.g., adalimumab, etanercept, infliximab, or tocilizumab), and a selective COX-2 inhibitor (e.g., lumiracoxib). [335] In embodiments, the anti-inflammatory agent is prednisone. In embodiments, the anti-inflammatory agent is hydrocortisone. In embodiments, the anti-inflammatory agent is diclofenac. In embodiments, the anti-inflammatory agent is etodolac. In embodiments, the anti-inflammatory agent is fenoprofen. In embodiments, the anti-inflammatory agent is flurbiprofen. In embodiments, the anti-inflammatory agent is ibuprofen. In embodiments, the anti-inflammatory agent is indomethacin. In embodiments, the anti-inflammatory agent is meclofenamate. In embodiments, the anti-inflammatory agent is mefenamic acid. In embodiments, the anti-inflammatory agent is nabumetone. In embodiments, the anti-inflammatory agent is naproxen. In embodiments, the anti-inflammatory agent is tolmetin. In embodiments, the anti-inflammatory agent is piroxicam. In embodiments, the anti-inflammatory agent is celecoxib. In embodiments, the anti-inflammatory agent is etoricoxib. In embodiments, the anti-inflammatory agent is aspirin. In embodiments, the anti-inflammatory agent is meloxicam. In embodiments, the anti-inflammatory agent is apremilast. In embodiments, the anti-inflammatory agent is an anti-cytokine agent. In embodiments, the anti- cytokine agent is adalimumab, etanercept, infliximab, or tocilizumab. In embodiments, the anti-inflammatory agent is a selective COX-2 inhibitor. In embodiments, the selective COX-2 inhibitor is lumiracoxib. 4. Anxiolytic Agents [336] In embodiments, the second agent is an anxiolytic agent. “Anxiolytic agent” may refer to an agent used for treatment of anxiety disorders and their related psychological and physical symptoms. Anxiolytic agents work in different ways to reduce anxiety, such as by increasing or decreasing cell activity, by slowing 2023-12-14 down activity in the sympathetic nervous system, or by modulating monoaminergic neurotransmission. [337] In embodiments, the anxiolytic agent is non-addictive (e.g., is not known to be habit-forming). In embodiments, an anxiolytic agent is selected from the group consisting of benzodiazepines, azapirones (e.g., buspirone) , alpha blockers, beta blockers, antidepressants, barbiturates, nonbenzodiazepine sedatives, hypnotics (e.g., zolpidem, zaleplon, and zopiclone), nefazodone, pregabalin, mirtazapine, and gabapentin. In embodiments, the beta blocker is propranolol. [338] In embodiments, the anxiolytic agent is a benzodiazepine. In embodiments, the benzodiazepine is lorazepam. In embodiments, the benzodiazepine is diazepam. In embodiments, the benzodiazepine is alprazolam. In embodiments, the benzodiazepine is clonazepam. In embodiments, the benzodiazepine is chlordiazepoxide. In embodiments, the benzodiazepine is chlordiazepoxide/clidinium bromide. [339] In embodiments, the anxiolytic agent is not a benzodiazepine. In embodiments, the benzodiazepine is not lorazepam. In embodiments, the benzodiazepine is not diazepam. In embodiments, the benzodiazepine is not alprazolam. In embodiments, the benzodiazepine is not clonazepam. In embodiments, the benzodiazepine is not chlordiazepoxide. In embodiments, the benzodiazepine is not chlordiazepoxide/clidinium bromide. [340] In embodiments, the anxiolytic agent is a barbiturate. In embodiments, the barbiturate is pento- barbital. In embodiments, the barbiturate is phenobarbital. In embodiments, the barbiturate is amobarbital. [341] In embodiments, the anxiolytic agent is an azapirone. In embodiments, the anxiolytic agent is a mirtazapine. In embodiments, the anxiolytic agent is an alpha blocker. In embodiments, the anxiolytic agent is a beta blocker. In embodiments, the anxiolytic agent is a pentobarbital. In embodiments, the anxiolytic agent is a nonbenzodiazepine sedative. In embodiments, the anxiolytic agent is a hypnotic. In embodiments, the anxiolytic agent is nefazodone. In embodiments, the anxiolytic agent is a pregabalin. In embodiments, the anxiolytic agent is mirtazapine. In embodiments, the anxiolytic agent is gabapentin. [342] In embodiments, the anxiolytic agent is baclofen, a GABA _B receptor agonist at pre- and post-synaptic neurons. In some embodiments, the anxiolytic agent is cyclobenzaprine, a muscle relaxant similar to TCAs. [343] In some embodiments, the anxiolytic agent is also an antidepressant. In some other embodiments, the anxiolytic agent is not also an antidepressant. 5. Antidepressants [344] In embodiments, the second agent is an antidepressant. “Antidepressant” may refer to an agent that can be used to treat depressive disorders, some anxiety disorders, some conditions associated with chronic pain, and used to help manage some addictions. There are many types of antidepressants, most of which work by altering the levels of monoaminergic neurotransmitters. [345] In embodiments, the second agent is an antidepressant. In embodiments, the antidepressant is a selective serotonin reuptake inhibitor (SSRI), a selective norepinephrine reuptake inhibitor (NRI), a serotonin and norepinephrine reuptake inhibitor (SNRI), a dual norepinephrine/dopamine reuptake inhibitor (NDRI), a 2023-12-14 tricyclic antidepressant (TCA), a noradrenaline and specific serotonergic antidepressant (NaSSA), a serotonin antagonist and reuptake inhibitor (SARI), and a norepinephrine-dopamine disinhibitor (NDDI). [346] In embodiments, the antidepressant is a selective serotonin reuptake inhibitor (SSRI). In embodiments, the SSRI is selected from the group consisting of fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, vortioxetine and vilazodone. In embodiments, the SSRI is fluoxetine. In embodiments, the SSRI is sertraline. In embodiments, the SSRI is fluvoxamine. In embodiments, the SSRI is citalopram. In embodiments, the SSRI is vortioxetine. In embodiments, the SSRI is escitalopram. In embodiments, the SSRI is vilazodone. [347] In embodiments, the antidepressant is not a SSRI. In embodiments, the SSRI is not any of fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, vortioxetine, and vilazodone. In embodiments, the SSRI is not fluoxetine. In embodiments, the SSRI is not sertraline. In embodiments, the SSRI is not fluvoxamine. In embodiments, the SSRI is not citalopram. In embodiments, the SSRI is not vortioxetine. In embodiments, the SSRI is not escitalopram. In embodiments, the SSRI is not vilazodone. [348] In embodiments, the antidepressant is a selective norepinephrine reuptake inhibitor (NRI) . In embodiments, the therapeutic agent is selected from the group consisting of atomoxetine and reboxetine. In embodiments, the NRI is atomoxetine. In embodiments, the NRI is reboxetine. [349] In embodiments, the antidepressant is a serotonin and norepinephrine reuptake inhibitor (SNRI). In embodiments, the SNRI is selected from the group consisting of desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine. In embodiments, the SNRI is desvenlafaxine. In embodiments, the SNRI is duloxetine. In embodiments, the SNRI is levomilnacipran. In embodiments, the SNRI is milnacipran. In embodiments, the SNRI is venlafaxine. [350] In embodiments, the antidepressant is a dual norepinephrine/dopamine reuptake inhibitor (NDRI). In embodiments, the NDRI is selected from the group consisting of amineptine, bupropion, desoxypipradrol, dexmethylphenidate, difemetorex, diphenylprolinol, ethylphenidate, fencamfamine, fencamine, lefetamine, methylenedioxypyrovalerone, methylphenidate, nomifensine, O-2172, phenylpiracetam, pipradrol, prolintane, pyrovalerone, solriamfetol, tametraline, and WY-46824. In embodiments, the NDRI is amineptine. In embodiments, the NDRI is bupropion. In embodiments, the NDRI is desoxypipradrol. In embodiments, the NDRI is dexmethylphenidate. In embodiments, the NDRI is difemetorex. In embodiments, the NDRI is diphenylprolinol. In embodiments, the NDRI is methylphenidate. In embodiments, the NDRI is fencamfamine. In embodiments, the NDRI is fencamine. In embodiments, the NDRI is lefetamine. In embodiments, the NDRI is methylenedioxypyrovalerone. In embodiments, the NDRI is methylphenidate. In embodiments, the NDRI is nomifensine. In embodiments, the NDRI is O-2172. In embodiments, the NDRI is phenylpiracetam. In embodiments, the NDRI is pipradrol. In embodiments, the NDRI is prolintane. In embodiments, the NDRI is pyrovalerone. In embodiments, the NDRI is solriamfetol. In embodiments, the NDRI is tametraline. In embodiments, the NDRI is WY-46824. 2023-12-14 [351] In embodiments, the antidepressant is a tricyclic antidepressant (TCA). In embodiments, the TCA is selected from the group consisting of amitriptyline, doxepin, clomipramine, nortriptyline, imipramine, desipramine, protriptyline, dosulepin, maprotiline, trimipramine and amoxapine. In embodiments, the TCA is amitriptyline. In embodiments, the TCA is doxepin. In embodiments, the TCA is clomipramine. In embodiments, the TCA is nortriptyline. In embodiments, the TCA is imipramine. In embodiments, the TCA is desipramine. In embodiments, the TCA is protriptyline. In embodiments, the TCA is dosulepin. In embodiments, the TCA is maprotiline. In embodiments, the TCA is trimipramine. In embodiments, the TCA is amoxapine. [352] In embodiments, the antidepressant is not a tricyclic antidepressant (TCA). In embodiments, the TCA is not any of amitriptyline, doxepin, clomipramine, nortriptyline, imipramine, desipramine, protriptyline, dosulepin, maprotiline, trimipramine, and amoxapine. In embodiments, the TCA is not amitriptyline. In embodiments, the TCA is not doxepin. In embodiments, the TCA is not clomipramine. In embodiments, the TCA is not nortriptyline. In embodiments, the TCA is not imipramine. In embodiments, the TCA is not desipramine. In embodiments, the TCA is not protriptyline. In embodiments, the TCA is not dosulepin. In embodiments, the TCA is not maprotiline. In embodiments, the TCA is not trimipramine. In embodiments, the TCA is not amoxapine. [353] In embodiments, the antidepressant is a noradrenaline and specific serotonergic antidepressant (NaSSA). In embodiments, the NaSSA is selected from the group consisting of aptazapine, esmirtazapine, mianserin, mirtazapine, and setiptiline (teciptiline). In embodiments, the NaSSA is aptazapine. In embodiments, the NaSSA is esmirtazapine. In embodiments, the NaSSA is mianserin. In embodiments, the NaSSA is mirtazapine. In embodiments, the NaSSA is setiptiline (teciptiline). [354] In embodiments, the antidepressant is a serotonin antagonist and reuptake inhibitor (SARI). In embodiments, the SARI is selected from the group consisting of etoperidone, lorpiprazole, mepiprazole, nefazodone, and trazodone. In embodiments, the SARI is etoperidone. In embodiments, the SARI is lorpiprazole. In embodiments, the SARI is mepiprazole. In embodiments, the SARI is nefazodone. In embodiments, the SARI is trazodone. [355] In embodiments, the antidepressant is a norepinephrine-dopamine disinhibitor (NDDI). In embodiments, the NDDI is selected from the group consisting of agomelatine, fluoxetine, flibanserin, and mirtazapine. In embodiments, the NDDI is agomelatine. In embodiments, the NDDI is fluoxetine. In embodiments, the NDDI is flibanserin. In embodiments, the NDDI is mirtazapine. [356] In embodiments, the antidepressant is selected from the group consisting of amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine, phenelzine, tranylcypromine, isocarboxazid, selegiline, mirtazapine, nefazodone, trazodone, bupropion, neurotropic agents, adaptogens, actoprotectors, nootropics, eugeroics, racetams, antihypoxants, cognitive enhancers (e.g., vitamin D such as vitamin D ₃ , d-D-serine, L-serine, caffeine, L-theanine, creatine, 2023-12-14 bacopa monnieri, rhodiola rosea, panax ginseng, ginkgo biloba, tanakan, salvia officinalis, lavandulaefolia, centella asiatica, nicotine, noopept, piracetam, phenotropil, amphetamines, cholinergics, citicoline, choline bitartrate, alpha-GPC, ethomersol, bemithyl, pyrazidol, actovegin forte, glutamine, bemethyl, mildronate, phenibut, amphetamine/dextroamphetamine, armodafinil, modafinil, and phenylpiracetam), potassium orotate, asparkam, psychedelics, entactogens, and empathogens (e.g., 3,4-methylenedioxymethamphetamine, paramethoxyamphetamine, 4-bromo-2,5-dimethoxyphenethylamine, 2,5-dimethoxy-4-methylamphetamine, trimethoxyamphetamine, tryptamines, benzofuran, ibogoids and iboga alkaloids, ergolines and lysergamides, phenethylamines, benzocyclobutene derivatives, NBOMe derivatives, NBOH derivatives, NBMD derivatives, NBF derivatives, 3C family (3,5-dimethoxy, 4-substituted amphetamines) ( see, e.g. , Elman et al. Neurosci. Biobehav. Rev. 2022;134:104482)), DOx family (2,5-dimethoxy, 4-substituted amphetamines), phenylcyclopropylamine derivatives, DMMDA, DMMDA-2, benzoxazines, cannabinoids, harmaline, harmala alkaloids, other beta-carbolines, ayahuasca, salvinorin A, salvinorin B, methoxymethyl, piperazines, myristicin, elemicin, cryogenine certain heimia species, atropine, scopolamine, hyoscyamine, psilocybin, psilocin, DMT, 5-MeO-DMT, LSD, ketamine, esketamine, the active constituents of certain Solanaceae species, ibotenic acid, muscimol, and other active constituents of Amanita muscaria mushrooms), solriamfetol, vilazodone, atomoxetine, milnacipran, dosulepin, duloxetine, escitalopram, venlafaxine, citalopram, fluoxetine, fluvoxamine, vortioxetine, reboxetine, sertraline, paroxetine, esketamine, ketamine, dextromethorphan/bupropion, naltrexone/bupropion, and lithium. In some embodiments, the cognitive enhancer is modafinil. [357] In embodiments, the antidepressant is amitriptyline. In embodiments, the antidepressant is amoxapine. In embodiments, the antidepressant is clomipramine. In embodiments, the antidepressant is desipramine. In embodiments, the antidepressant is doxepin. In embodiments, the antidepressant is imipramine. In embodiments, the antidepressant is maprotiline. In embodiments, the antidepressant is nortriptyline. In embodiments, the antidepressant is protriptyline. In embodiments, the antidepressant is trimipramine. In embodiments, the antidepressant is phenelzine. In embodiments, the antidepressant is tranylcypromine. In embodiments, the antidepressant is isocarboxazid. In embodiments, the antidepressant is selegiline. In embodiments, the antidepressant is mirtazapine. In embodiments, the antidepressant is nefazodone. In embodiments, the antidepressant is trazodone. In embodiments, the antidepressant is bupropion. In embodiments, the antidepressant is a neurotrophic agent. In embodiments, the antidepressant is an adaptogen. In embodiments, the antidepressant is an actoprotector. [358] In embodiments, the antidepressant is a nootropic. In embodiments, the antidepressant is an eugeroic. In embodiments, the antidepressant is a racetam. In embodiments, the antidepressant is an antihypoxant. In embodiments, the antidepressant is a cognitive enhancer. In embodiments, the cognitive enhancer is vitamin D (e.g., vitamin D ₃ ). In embodiments, the antidepressant is potassium orotate. In embodiments, the antidepressant is asparkam. In embodiments, the antidepressant is a psychedelic. 2023-12-14 [359] In embodiments, the antidepressant is solriamfetol. In embodiments, the antidepressant is vilazodone. In embodiments, the antidepressant is atomoxetine. In embodiments, the antidepressant is milnacipran. In embodiments, the antidepressant is dosulepin. In embodiments, the antidepressant is duloxetine. In embodiments, the antidepressant is escitalopram. In embodiments, the antidepressant is venlafaxine. In embodiments, the antidepressant is citalopram. In embodiments, the antidepressant is fluoxetine. In embodiments, the antidepressant is fluvoxamine. In embodiments, the antidepressant is vortioxetine. In embodiments, the antidepressant is reboxetine. In embodiments, the antidepressant is sertraline. In embodiments, the antidepressant is paroxetine. In embodiments, the antidepressant is esketamine. In embodiments, the antidepressant is ketamine. In embodiments, the antidepressant is dextromethorphan/bupropion. In embodiments, the antidepressant is naltrexone/bupropion. In embodiments, the antidepressant is lithium. [360] In embodiments, the antidepressant is not a psychedelic. In embodiments, the antidepressant is not atropine. In embodiments, the antidepressant is not hyoscyamine. In embodiments, the antidepressant is not scopolamine. In embodiments, the antidepressant is not bupropion. In embodiments, the antidepressant is not mirtazapine. In embodiments, the antidepressant is not an amphetamine. [361] In embodiments, the antidepressant is an MAOI, such as any of the MAOIs described herein. In embodiments, the antidepressant is not an MAOI. In some embodiments, the antidepressant is not any of the MAOIs described or expressly listed herein. [362] In some embodiments, the antidepressant is also an anxiolytic agent. In some embodiments, the antidepressant is not also an anxiolytic agent. 6. Antihypertensive Agents [363] In embodiments, the second agent is an antihypertensive agent. “Antihypertensive agent” may refer to an agent that lowers blood pressure when administered to a subject. Antihypertensive agents are commonly used for treatment of hypertension, or high blood pressure. [364] In embodiments, the antihypertensive agent is selected from the group consisting of nimodipine, diuretics, beta blockers, ACE inhibitors, Angiotensin II receptor blockers, calcium channel blockers, alpha blockers, alpha-2 receptor agonists, combined alpha and beta blockers, central agonists, peripheral adrenergic inhibitors, and vasodilators. [365] In embodiments, the antihypertensive agent is nimodipine. In embodiments, the antihypertensive agent is a diuretic. In embodiments, the antihypertensive agent is a beta blocker. In embodiments, the antihypertensive agent is an ACE inhibitor. In embodiments, the antihypertensive agent is an Angiotensin II receptor blocker. In embodiments, the antihypertensive agent is a calcium channel blocker. In embodiments, the antihypertensive agent is an alpha blocker. In embodiments, the antihypertensive agent is an alpha-2 receptor agonist. In embodiments, the antihypertensive agent is a combined alpha and beta blocker. In embodiments, the antihypertensive agent is a central agonist. In embodiments, the antihypertensive agent is 2023-12-14 a peripheral adrenergic inhibitor. In embodiments, the antihypertensive agent is a vasodilator. C. Additional Active Agents [366] In embodiments, one or more disclosed pharmaceutical agents can also be administered together with one or more additional active agents. Where a first agent, such as a RIMA, is administered with an additional active agent, the additional active agent may be referred to as the “second” agent. Where a first agent, such as a RIMA, is administered with a second agent such as in any of the classes above, together with another agent, such agent may be referred to as the “additional active agent.” Broadly, any agent not in the classes above (or, categorized for purposes of a combination as not in the classes above) may be referred to generally as an “additional active agent,” but where an agent that is in the classes above (or, categorized for purposes of a combination as in the classes above) is administered as a third or further agent in a therapeutic combination, it may be referred to as an “additional active agent”; i.e., any agent beyond the “first” and “second” agent in a combination may be referred to as an “additional active agent.” [367] In some embodiments, methods therefore may comprise administration of a RIMA and a second agent. In embodiments, methods may comprise administration of a RIMA and an additional active agent. In embodiments, methods may comprise administration of a RIMA, a second agent, and an additional active agent. Yet other methods may comprise administration of a RIMA and more than one second agent; a RIMA and more than one additional active agent; a RIMA, more than one second agent, and an additional active agent; a RIMA, a second agent, and more than one additional active agent; or a RIMA, more than one second agent, and more than one additional active agent. [368] Any embodiment also may comprise more than one RIMA, such as 2, 3, 4, 5, or more than 5 RIMAs. [369] In embodiments, the additional active agent is an amino acid, antioxidant, anti-inflammatory agent, analgesic, antineuropathic or antinociceptive agent, antimigraine agent, anxiolytic, antidepressant, antipsychotic, anti-PTSD agent, cannabinoid, dissociative (e.g., dissociative anesthetic), immunostimulant, anti-cancer agent, antiemetic, orexigenic, antiulcer agent, anticholinergic agent, anti-ischemic agent, antihistamine (e.g., diphenhydramine, meclizine, promethazine, dimenhydrinate) , antihypertensive, antimigraine agent, anticonvulsant, antiepileptic, bronchodilator, mood stabilizer, neuroprotectant, serotonergic agent, neuroactive agent, entactogen or empathogen, entheogen, psychedelic, monoamine oxidase inhibitor (MAOI), tryptamine, terpene, phenethylamine, sedative, serotonergic agent, stimulant, opioid modulator, N-methyl-D-aspartate (NMDA) receptor agent, vitamin, SSRI, SNRI, NRI, NDRI, TCA, benzodiazepine, or phosphodiesterase inhibitor (e.g., a PDE-1 inhibitor, a PDE-2 inhibitor, a PDE-3 inhibitor, a PDE-4 inhibitor such as apremilast, or a PDE-5 inhibitor). [370] In embodiments, the additional active agent is a tryptamine psychedelic or entactogen. Exemplary tryptamine psychedelics and entactogens include those described in Shulgin and Shulgin, TiHKAL: The Continuation, Transform Press (1997), which is incorporated by reference as if fully set forth herein. [371] In embodiments, the additional active agent is a phenethylamine psychedelic or entactogen. 2023-12-14 Exemplary phenethylamine psychedelics and entactogens include those described in Shulgin and Shulgin, PiHKAL: A Chemical Love Story, Transform Press (1991)), and Oeri. Psychopharmacol ., 2021;35(5):512- 536, both of which are incorporated by reference as if fully set forth herein. [372] Additional active agents may be in ion, freebase, or salt form, include polymorphs, and may be isomers, and include single enantiomers and enantiomeric mixtures of any proportions. [373] In embodiments, the additional active agent is a NMDA receptor agent (“NMDA agent”). In embodiments, the NMDA agent is a partial NMDA receptor agonist, such as D-cycloserine (DCS). In embodiments, the NMDA agent is a partial agonist and is NRX-1074 or rapastinel (GLYX-13). In embodiments, the NMDA agent is any of plazinemdor, rapastinel, LY-2140023, NYX-458, NYX-783, NYX-2925, NRX-1074, SAGE-718, a substituted 1,2,3-triazole NMDA modulator such as disclosed in WO2017/139428A1, a spiro-lactam NMDA modulator such as disclosed in WO2018/026798A1, and an NMDA modulator disclosed in WO2017/066590A1 (see, e.g., id. at [0006]). In embodiments, the NMDA agent is an NMDA antagonist. In embodiments the NMDA antagonist is memantine, amantadine, rimantadine, nitromemantine (YQW-36), or acamprosate. In embodiments, the NMDA agent is an NMDA antagonist, and the NMDA antagonist is acamprosate. In embodiments the NMDA antagonist is pethidine, levorphanol, methadone, dextropropoxyphene, tramadol, or ketobemidone. In embodiments the NMDA antagonist is dextromethorphan (DXM), dextrorphan, or dextrallorphan (DXA). In embodiments, the NMDA antagonist is gacyclidine (GK-11), neramexane, lanicemine (AZD6765), diphenidine, dizocilpine (MK-801), 8a-phenyldecahydroquinoline (8A-PDHQ), remacemide, ifenprodil, traxoprodil (CP-101,606), eliprodil (SL-82.0715), etoxadrol (CL-1848C), dexoxadrol, WMS-2539, NEFA, delucemine (NPS-1506), aptiganel (Cerestat; CNS-1102), midafotel (CPPene; SDZ EAA 494), dexanabinol (HU-211 or ETS2101), selfotel (CGS-19755), 7-chlorokynurenic acid (7-CKA), 5,7-dichlorokynurenic acid (5,7-DCKA), L-683344, L-689560, L-701324, GV150526A, GV196771A, CERC-301 (MK-0657), atomoxetine, LY-235959, CGP 61594, CGP 37849, CGP 40116 or CGP 37849, LY-233536, PEAQX (NVP-AAM077), ibogaine or noribogaine (or an ibogaine metabolite, ibogaine analog, or ibogaine derivative), Ro 25-6981, GW468816, EVT-101, indantadol, perzinfotel (EAA-090), SSR240600, 2-MDP (U-23807A) or AP-7. In embodiments, the NMDA antagonist is ketamine (and its analogs, e.g., tiletamine), phencyclidine (and its analogs, e.g., tenocyclidine, eticyclidine, rolicyclidine), or methoxetamine (and its analogs). In embodiments the NMDA antagonist is ketamine, S-ketamine, R-ketamine, or a non-racemic mixture of ketamine enantiomers. In embodiments, the NMDA antagonist is a ketamine metabolite, such as any of the 12 HNK metabolites formed from the metabolism of ketamine in vivo, including any of the stereoselective metabolites of S- or R-ketamine, such as (R,S)-norketamine (NK), (R,S)-dehydronorketamine, hydroxyketamines, and hydroxy- norketamines (HNKs), including (2S,6S;2R,6R)-HNK, (2R,4R;2S,4S-2S,6R;2R,6S)-HNK, and (2R,4S;2S,4R-2S,5S;2R,5R)-HNK (Farmer, 2020). In embodiments, the NMDA antagonist is a ketamine analog such as methoxetamine (2-MeO-2-deschloroketamine, MXE), 3-MeO-PCE, KEA-1010, N-ethyldeschloroketamine (2'-Oxo-PCE, 2023-12-14 O-PCE), 2-fluoro-deschloroketamine [2-(2-fluorophenyl)-2-methylamino-cyclohexanone] (2-FDCK), deschloro-ketamine (2-phenyl-2- methylamino-cyclohexanone), DXE (2'-Oxo-PCM, aka DCK), alkyne-norketamine (A-NK), and the like. In embodiments, the NMDA antagonist is an arylcyclohexylamine or an arylcyclohexylamine derivative, such as disclosed in, e.g., WO2022/047256A1, US2022/0041540A1, and WO2021/255737A1, incorporated by reference as if fully set forth. [374] In embodiments, the additional active agent is a phosphodiesterase inhibitor. In embodiments, the phosphodiesterase inhibitor is a PDE-1 inhibitor. In embodiments, the phosphodiesterase inhibitor is a PDE-2 inhibitor. In embodiments, the phosphodiesterase inhibitor is a PDE-3 inhibitor. In embodiments, the phosphodiesterase inhibitor is a PDE-4 inhibitor. In embodiments, the PDE-4 inhibitor is apremilast. In embodiments, the phosphodiesterase inhibitor is a PDE-5 inhibitor. [375] In embodiments, the additional active agent is an anti-ischemic agent. In embodiments, the anti-ischemic agent is meldonium. [376] In embodiments, the additional active agent is an antimigraine agent. In embodiments, the antimigraine agent is a triptan. [377] In embodiments, the additional active agent is an anticonvulsant. In embodiments, the anticonvulsant is selected from the group consisting of carbamazepine, oxcarbazepine, lamotrigine, valproic acid, topiramate, levetiracetam, brivaracetam, and seletracetam . In embodiments, the anticonvulsant is carbamazepine. In embodiments, the anticonvulsant is oxcarbazepine. In embodiments, the anticonvulsant is lamotrigine. In embodiments, the anticonvulsant is valproic acid. In embodiments, the anticonvulsant is topiramate. In embodiments, the anticonvulsant is levetiracetam. In embodiments, the anticonvulsant is brivaracetam. In embodiments, the anticonvulsant is seletracetam. [378] In embodiments, the additional active agent is a serotonergic agent. In embodiments, the serotonergic agent is ondansetron. In embodiments, the additional active agent is not a serotonergic agent. In embodiments, the serotonergic agent is not ondansetron. [379] In embodiments, the additional active agent is an antihistamine. In embodiments, the antihistamine is vistaril. In embodiments, the additional active agent is not an antihistamine. In embodiments, the antihistamine is not vistaril. [380] In embodiments, the additional active agent is an anticraving agent. In embodiments, the anticraving agent is any of ondansetron, disulfiram, buprenorphine, topiramate, rimonabant, bupropion, modafinil, vigabatrin, and varenicline. [381] In embodiments, the additional active agent is an antidepressant. In embodiments, the antidepressant is bupropion. In embodiments, the antidepressant is mirtazapine. In embodiments, the additional active agent is not an antidepressant. In embodiments, the antidepressant is not bupropion. In embodiments, the antidepressant is not mirtazapine. [382] In embodiments, the additional active agent is a mood stabilizer. In embodiments, the mood 2023-12-14 stabilizer is lithium. In embodiments, the additional active agent is a benzodiazepine. In embodiments, the additional active agent is an opioid modulator. In embodiments, the opioid modulator is naltrexone. In embodiments, the opioid modulator is vivitrol. In embodiments, the opioid modulator is buprenorphine. In embodiments, the additional active agent is an SSRI. In embodiments, the additional active agent is a TCA. In embodiments, the additional active agent is a MAOI. In embodiments, the additional active agent is an anticholinergic agent. [383] In embodiments, the additional active agent is not a mood stabilizer. In embodiments, the mood stabilizer is not lithium. In embodiments, the additional active agent is not a benzodiazepine. In embodiments, the additional active agent is not an opioid modulator. In embodiments, the opioid modulator is not naltrexone. In embodiments, the opioid modulator is not vivitrol. In embodiments, the opioid modulator is not buprenorphine. In embodiments, the additional active agent is not a SSRI. In embodiments, the additional active agent is not a TCA. In embodiments, the additional active agent is not a MAOI. In embodiments, the additional active agent is not an anticholinergic agent. [384] In some embodiments, the additional active agent is a serotonergic agent. In embodiments, a “serotonergic agent” will be an agent that binds to, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at one or more serotonin receptors, including any one or more serotonin receptor subtypes. In embodiments, a serotonergic agent is not a psychedelic. In embodiments, a serotonergic agent binds to a serotonin receptor. In embodiments, a serotonergic agent indirectly affects a serotonin receptor, e.g., via interactions affecting the reactivity of other molecules at the serotonin receptor. In embodiments, a serotonergic agent is an agonist, e.g., an agent activating a serotonin receptor. In embodiments, a serotonergic agent is an antagonist, e.g., an agent binding but not activating a serotonin receptor, e.g., blocking a receptor. In embodiments, a serotonergic agent is an effector molecule, e.g., an agent binding to an enzyme for allosteric regulation. In embodiments, a serotonergic agent acts (either directly or indirectly) at more than one type of receptor, including receptors other than serotonergic or other monoaminergic receptors. In embodiments, a serotonergic agent blocks the serotonin transporter (SERT) and results in an elevation of the synaptic concentration of serotonin, and an increase of neurotransmission. In embodiments, a serotonergic agent acts as a reuptake modulator and inhibits the plasmalemmal transporter-mediated reuptake of serotonin from the synapse into the presynaptic neuron, leading to an increase in extracellular concentrations of serotonin and an increase in neurotransmission. In embodiments, a serotonergic agent inhibits the activity of one or both monoamine oxidase enzymes, resulting in an increase in concentrations of serotonin and an increase in neurotransmission. In embodiments, a serotonergic agent is an antidepressant or anxiolytic, such as an SSRI, serotonin-norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), monoamine oxidase inhibitor (MAOI), or atypical antidepressant. In other embodiments, a serotonergic agent is selected from the group consisting of: (1) serotonin transport inhibitors; (2) serotonin receptor modulators; (3) serotonin reuptake inhibitors; (4) serotonin and norepinephrine reuptake inhibitors; 2023-12-14 (5) serotonin dopamine antagonists; (6) monoamine reuptake inhibitors; (7) pyridazinone aldose reductase inhibitors; (8) stimulants of serotonin receptors; (9) stimulants of serotonin synthesis; (10) serotonin receptor agonists; (11) serotonin receptor antagonists; and (12) serotonin metabolites. Additional serotonergic agents will be known to those in the art, and can be found, for example, on DrugBank (https://go.drugbank.com). [385] In embodiments, the additional active agent is selected to provide synergistic effects. [386] In embodiments, additional active agents that may be employed in the disclosed methods include zolpidem tartrate, e.g., up to a maximum dose of 10 mg/day, or zaleplon, e.g., up to a maximum dose of 20 mg/day for insomnia as clinically indicated. Other examples include lorazepam for agitation at the discretion of the treating clinician. Administration of lorazepam within six hours of the administration of rating scales is preferably avoided. In other embodiments, concomitant administration of other active agents is not employed. For example, medications or drugs with prominent orexigenic/anorexigenic effects, e.g., anticholinergics, amphetamines, mood stabilizers, opioid analgesics, antidepressants including tricyclics, SSRIs, MAO inhibitors, bupropion, and mirtazapine, may be excluded from the methods described herein. [387] In embodiments, the additional active agent is another agent disclosed herein (e.g., a MAOI, antihyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antihypertensive agent, another agent used to treat PFAOMC in a subject). For example, in embodiments, a disclosed method comprises administering a RIMA in combination with a second agent (e.g., a monoamine oxidase inhibitor, antihyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antihypertensive agent, another agent used to treat PFAOMC in a subject). [388] An additional active agent may, in some embodiments, contribute to or provide an additional therapeutic effect, or contribute to or provide a synergistic effect. In embodiments, the additional active agent (equivalently, “additional therapeutic compound”) is selected to provide an additional therapeutic effect, such as antioxidant, anti-inflammatory, analgesic, antineuropathic, antinociceptive, antimigraine, anxiolytic, antidepressant, antipsychotic, anti-PTSD, immunostimulant, anti-cancer, antiemetic, orexigenic, antiulcer, anticholinergic, anti-ischemic, antihistamine, antihypertensive, antimigraine, anticonvulsant , antiepileptic, bronchodilator, mood stabilizing, neuroprotective, serotonergic, entactogenic, empathogenic, entheogenic, euphoric, psychedelic, sedative, vasodilatory, opioidergic, and stimulant effects. [389] For any of the disclosed classes of agents, additional agents in such classes will be known to those in the art, or can be found according to skill in the art, for example, on DrugBank (https://go.drugbank.com/). D. Combinations [390] In embodiments, a method comprises administering a RIMA and an antihyperglycemic agent. In embodiments, a method comprises administering moclobemide and an antihyperglycemic agent. In embodiments, a method comprises administering a RIMA and metformin. In embodiments, a method comprises administering moclobemide and metformin. [391] In embodiments, administering a RIMA in combination with an antihyperglycemic agent treats a 2023-12-14 psychological factor. In embodiments, administering moclobemide in combination with an antihyperglycemic agent treats a psychological factor. In embodiments, administering a RIMA in combination with metformin treats a psychological factor. In embodiments, administering moclobemide in combination with metformin treats a psychological factor. [392] In embodiments, administering a RIMA in combination with an antihyperglycemic agent synergistically treats a psychological factor. In embodiments, administering moclobemide in combination with an antihyperglycemic agent synergistically treats a psychological factor. In embodiments, administering a RIMA in combination with metformin synergistically treats a psychological factor. In embodiments, administering moclobemide in combination with metformin synergistically treats a psychological factor. [393] In embodiments, administering a RIMA in combination with an antihyperglycemic agent treats a psychological factor and the other medical condition. In embodiments, administering moclobemide in combination with an antihyperglycemic agent treats a psychological factor and the other medical condition. In embodiments, administering a RIMA in combination with metformin treats a psychological factor and the other medical condition. In embodiments, administering moclobemide in combination with metformin treats a psychological factor and the other medical condition. [394] In embodiments, administering a RIMA in combination with an antihyperglycemic agent synergistically treats a psychological factor and the other medical condition. In embodiments, administering moclobemide in combination with an antihyperglycemic agent synergistically treats a psychological factor and the other medical condition. In embodiments, administering a RIMA in combination with metformin synergistically treats a psychological factor and the other medical condition. In embodiments, administering moclobemide in combination with metformin synergistically treats a psychological factor and the other medical condition. [395] In embodiments, administering a RIMA in combination with an antihyperglycemic agent provides synergistic effects in the treatment of PFAOMC. In embodiments, administering moclobemide in combination with an antihyperglycemic agent provides synergistic effects in the treatment of PFAOMC. In embodiments, administering a RIMA in combination with metformin provides synergistic effects in the treatment of PFAOMC. In embodiments, administering moclobemide in combination with metformin provides synergistic effects in the treatment of PFAOMC. [396] Other non-limiting exemplary synergistic combinations include, as examples, moclobemide and nimodipine; moclobemide and propranolol; moclobemide and solriamfetol; moclobemide and modafinil; moclobemide and lumiracoxib; and moclobemide and ibuprofen. [397] Metformin improves glucoregulatory function in a subject by increasing insulin sensitivity in conjunction with decreased gluconeogenesis in the liver. Metformin also exerts robust antioxidant and anti-inflammatory effects, such as decreased growth/differentiation factor 15 ( see, e.g ., Obi et al. J Diabetes Res.2016;2016:1635361; Bai et al. Front Pharmacol. 2021;12:622262; Dehkordi et al. J Renal Injury 2023-12-14 Prevention .2018;8(1):54-61; and Bootcov et al. Proc. Natl. Acad. Sci. U.S.A .1997;94(21):11514-11519). Without being bound by theory, metformin is expected to improve affective states in preclinical models and in clinical populations, attributable to its anti-inflammatory, antioxidant, neuro-restorative, and neuro-protective effects ( see, e.g. , Khedr et al., Naunyn Schmiedebergs Arch Pharmacol.2018;391(4):407-422; Poggini et al. Neural Plast.2019;2019:4651031; Hosseini et al. World J Biol Psychiatry.202217:1-14; Abrahamian et al. Neuropsychiatr Dis Treat. 2009;5:261-6; Guo et al. Clin Exp Pharmacol Physiol. 2014;41(9):650-6; Abrahamian et al. Neuropsychiatr Dis Treat.2012;8:355-60; Isoda et al. Arterioscler Thromb Vasc Biol. 2006;26(3):611-7; and Afshari et al. Spinal Cord.2018;56(11):1032-1041). [398] In embodiments, a disclosed method comprises administering a RIMA and an antihypertensive agent. In embodiments, a disclosed method comprises administering moclobemide and an antihypertensive agent. In embodiments, a disclosed method comprises administering moclobemide and nimodipine ( see, e.g. , Taragano et al. Int. Psychogeriatr.2005;17(3):487-498). [399] In embodiments, a disclosed method comprises administering a RIMA and an anxiolytic agent. In embodiments, a disclosed method comprises administering moclobemide and an anxiolytic agent. In embodiments, a disclosed method comprises administering moclobemide and propranolol. In embodiments, a disclosed method comprises administering moclobemide and lorazepam. [400] In embodiments, a disclosed method comprises administering a RIMA and an antidepressant. In embodiments, a disclosed method comprises administering moclobemide and an antidepressant. In embodiments, a disclosed method comprises administering moclobemide and solriamfetol. In embodiments, a disclosed method comprises administering moclobemide and bupropion. In embodiments, a disclosed method comprises administering moclobemide and modafinil. [401] In embodiments, a disclosed method comprises administering a RIMA and an antioxidant. In embodiments, a disclosed method comprises administering moclobemide and an antioxidant. In embodiments, a disclosed method comprises administering moclobemide and N-acetylcysteine ( see, e.g. , Scapagnini et al. CNS Drugs. 2012;26(6):477-490). In embodiments, administering moclobemide in combination with an antioxidant provides synergistic effects. [402] There is evidence that suggests that inhibition of MAO-A may result in additive or synergistic antioxidant effects, including targeting different free radicals and various junctures of oxidative stress, and increasing concentrations of glutathione, nitric oxide, and superoxide dismutase ( see, e.g. , Herraiz et al. Biomed. Res. Int.2018:4810394; Krauss et al. Med. Sci. Monit.2003;9(11):BR389-393; and Albayrak et al. Eurasian J. Med.2015;47(1):32-40). Antioxidant effects may be measured in humans via diminished markers of DNA damage by oxidative stress ( see, e.g. , Jorgensen et al. JAMA Psychiatry .2022;79(9):920-931; and Palmieri et al. Eur. Rev. Med. Pharmacol. Sci .2007;11(5):309-342). [403] In embodiments, a disclosed method comprises administering a RIMA and an anti-inflammatory agent. In embodiments, a disclosed method comprises administering moclobemide and an anti-inflammatory 2023-12-14 agent. In embodiments, a disclosed method comprises administering moclobemide and ibuprofen. In embodiments, a disclosed method comprises administering moclobemide and a selective COX-2 inhibitor ( see, e.g. , Bay-Richter et al. Front Pharmacol.2022;13:909981). In embodiments, a disclosed method comprises administering moclobemide and lumiracoxib. In embodiments, administering moclobemide in combination with an anti-inflammatory agent provides synergistic effects. [404] Use of moclobemide may result in anti-inflammatory effects, such as decreasing the amount of inflammatory cytokines in the blood ( see, e.g. , Lin et al. J. Affect Disord.2000;58(1):69-74; and Bielecka et al. Naunyn Schmiedebergs Arch Pharmacol. 2010;382(5-6):409-17). In some embodiments, use of an anti-inflammatory agent in combination with an MAOI, such as a RIMA, may result in additive or synergistic anti-inflammatory effects, such as improving insulin resistance and glucoregulatory function, which results in suppression of inflammatory responses and improved monoaminergic neurotransmission ( see, e.g ., Katsiki et al. J. Diabetes Complications. 2020;34(12):107723; Ostadkarampour et al. Front Pharmacol . 2021;12:676239; Yaribeygi et al. J. Cell Physiol.2019;234(6):8286-8294; and Gonzalez-Hunt et al. Current Opinion on Toxicology.2018;7:87-94). [405] For example, in embodiments, a disclosed method comprises administering one or more disclosed agents in combination with a nicotinamide adenine dinucleotide (NAD+) and enkephalinase inhibitor infusion ( IV1114589NAD) (see, e.g. , Blum et al. Curr Psychiatry Res Rev .2022;18(2):125-143). [406] In embodiments, a disclosed method comprises administering a RIMA and a neuroactive agent to treat PFAOMC in a subject that has an IRARD. In embodiments, a disclosed method comprises administering a RIMA and a neuroactive agent to treat PFAOMC in a subject that does not have an IRARD. [407] In some embodiments, exemplary combinations for treating PFAOMC, including in some such embodiments, treating both the psychological factor and the other medical condition, include the following: 1. Moclobemide (50-150 mg/day) and metformin (500-2500 mg/day) 2. Moclobemide (150-600 mg/day) and metformin (500-2500 mg/day) 3. Moclobemide (150-600 mg/day) and nimodipine (60-360 mg/day) 4. Moclobemide (150-600 mg/day) and propranolol (40-640 mg/day) 5. Moclobemide (150-600 mg/day) and solriamfetol (75-150 mg/day) 6. Moclobemide (150-600 mg/day) and modafinil (200-400 mg/day) 7. Moclobemide (150-600 mg/day) and lumiracoxib (200-400 mg/day) 8. Moclobemide (150-600 mg/day) and ibuprofen (400-3200 mg/day) [408] For each of the foregoing exemplary combinations where moclobemide is administered at a dosage of 150-600 mg/day, in an additional exemplary embodiment, moclobemide is administered at a dosage of 50-150 mg/day, together with the other pharmaceutical agent, for example at the dosage provided. [409] In some other embodiments, exemplary combinations for treating PFAOMC, including in some such embodiments, treating both the psychological factor and the other medical condition, include the following, 2023-12-14 wherein for each such embodiment the dosage administered will be as known to those of skill: 1. A RIMA, such as moclobemide, and a PDE-1 inhibitor , such as vinpocetine. 2. A RIMA, such as moclobemide, and a PDE-2 inhibitor , such as tofisopam. 3. A RIMA, such as moclobemide, and a PDE-3 inhibitor , such as milrinone. 4. A RIMA, such as moclobemide, and a PDE-4 inhibitor, such as apremilast. 5. A RIMA, such as moclobemide, and a PDE-5 inhibitor , such as dipyridamole. 6. A RIMA, such as moclobemide, and an antioxidant, such as N-acetylcysteine. 7. A RIMA, such as moclobemide, and an anti-ischemic agent, such as meldonium. 8. A RIMA, such as moclobemide, and an antioxidant, such as acetyl-L-carnitine. 9. A RIMA, such as moclobemide, and an NDRI, such as phenylpiracetam. 10. A RIMA, such as moclobemide, and a cognitive enhancer, such as vitamin D ₃. 11. A RIMA, such as moclobemide, and an antioxidant, such as L-methylfolate. 12. A RIMA, such as moclobemide, and an anxiolytic agent, such as buspirone. 13. A RIMA, such as moclobemide, and an anticonvulsant, such as carbamazepine. 14. A RIMA, such as moclobemide, and an anticonvulsant, such as oxacarbazepine. 15. A RIMA, such as moclobemide, and an anticonvulsant, such as lamotrigine. 16. A RIMA, such as moclobemide, and an anticonvulsant, such as valproic acid. 17. A RIMA, such as moclobemide, and an anticonvulsant, such as topiramate. 18. A RIMA, such as moclobemide, and an anticonvulsant, such as levetiracetam. 19. A RIMA, such as moclobemide, and an anticonvulsant, such as brivaracetam. 20. A RIMA, such as moclobemide, and an anticonvulsant, such as seletracetam. 21. A RIMA, such as moclobemide, and an anxiolytic agent, such as lorazepam. 22. A RIMA, such as moclobemide, and a benzodiazepine, such as diazepam. 23. A RIMA, such as moclobemide, and a benzodiazepine, such as alprazolam. 24. A RIMA, such as moclobemide, and a benzodiazepine, such as clonazepam. 25. A RIMA, such as moclobemide, and a benzodiazepine, such as chlordiazepoxide. 26. A RIMA, such as moclobemide, and a benzodiazepine, such as chlordiazepoxide/clidinium bromide. 27. A RIMA, such as moclobemide, and a mood stabilizer, such as lithium. 28. A RIMA, such as moclobemide, and an antimigraine agent, such as triptan. 29. A RIMA, such as moclobemide, and an anxiolytic agent, such as pentobarbital. 30. A RIMA, such as moclobemide, and an anxiolytic agent, such as phenobarbital. 31. A RIMA, such as moclobemide, and an anxiolytic agent, such as amobarbital. 32. A RIMA, such as moclobemide, and an NMDA receptor agent, such as acamprosate. 33. A RIMA, such as moclobemide, and an NMDA receptor agent, such as ketamine or esketamine. 34. A RIMA, such as moclobemide, and an opioid modulator, such as naltrexone. 2023-12-14 35. A RIMA, such as moclobemide, and an opioid modulator, such as vivitrol. 36. A RIMA, such as moclobemide, and an anticraving agent, such as buprenorphine. 37. A RIMA, such as moclobemide, and a psychedelic, such as psilocybin. [410] Further embodiments of the disclosed methods, compositions, and pharmaceutical kits include each of the above exemplary embodiments, but where moclobemide is substituted by another RIMA, such brofaromine, caroxazone, CX157, CX2614, eprobemide, metralindole, minaprine, pirlindole, or toloxatone. [411] Other embodiments of the disclosed methods, compositions, and pharmaceutical kits include each of the above exemplary embodiments, but where the second agent is substituted by another second agent, which may be from the same class, or which may be from another disclosed class of agents, such as another antihyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antidepressant, or antihypertensive agent, or any other broader, narrower, or other class of agents disclosed herein. [412] Yet other embodiments of the disclosed methods, compositions, and pharmaceutical kits include each of the above exemplary embodiments, further comprising an additional active agent disclosed herein. [413] Yet other embodiments comprise pharmaceutical compositions comprising both of the agents in each of the above exemplary embodiments, e.g., co-formulated as a fixed-dose combination drug (FDC). [414] In embodiments, “synergistic effects” will be understood to include increases in potency, bioactivity, bioaccessibility, bioavailability, or therapeutic effect, that are greater than the additive contributions of the components acting alone, and/or are greater than the contribution of the isolated agents on their own. Numerous methods known to those of skill in the art exist to determine whether there is synergy as to a particular effect, i.e., whether, when two or more components are mixed together, the effect is greater than the sum of the effects of the individual components when applied alone, thereby producing “1+1 > 2.” One such method is the isobologram analysis (or contour method) (Huang et al.2019). IV. Pharmaceutical Compositions [415] In some aspects, provided herein are compositions, such as pharmaceutical compositions, comprising the disclosed agents. “Pharmaceutical compositions” are those that include the disclosed agent(s) together in an amount (for example, in a unit dosage form) with a pharmaceutically acceptable carrier, diluent, or excipient. Some embodiments will not have a single carrier, diluent, or excipient, but will include multiple carriers, diluents, and/or excipients. Compositions can be prepared by standard formulation techniques such as disclosed in, e.g., Remington: The Science & Practice of Pharmacy (2020) 23th ed., Academic Press., Cambridge, Mass.; The Merck Index (1996) 12th ed., Merck Pub. Group, Whitehouse, N.J.; Pharm. Principles of Solid Dosage Forms (1993), Technomic Pub. Co., Inc., Lancaster, Pa.; and Ansel & Stoklosa, Pharm. Calculations (2001) 11th ed., Lippincott Williams & Wilkins, Baltimore, Md.; & Poznansky et al. Drug Delivery Systems (1980), R.L. Juliano, ed., Oxford, N.Y., pp.253-315). [416] “Pharmaceutically acceptable” used in connection with an excipient, carrier, diluent, or other ingredient means the ingredient is generally safe and, within the scope of sound medical judgment, suitable 2023-12-14 for use in contact with cells of humans and animals without undue toxicity, irritation, allergic response, or complication, commensurate with a reasonable risk/benefit ratio. [417] In embodiments, pharmaceutical compositions comprising a disclosed agent may be administered alone or in combination with one or more pharmaceutical compositions comprising a disclosed agent. [418] In embodiments, pharmaceutical compositions comprising a disclosed agent can be administered by a variety of routes including oral, mucosal (e.g., buccal, sublingual), rectal, transdermal, subcutaneous, intravenous, intramuscular, inhaled, and intranasal. In embodiments, the agents employed in the methods of this invention are effective as oral, mucosal (e.g., buccal, sublingual), rectal, transdermal, subcutaneous, intravenous, intramuscular, inhaled, and intranasal compositions. Such compositions are prepared in a manner known in the art and comprise at least one active agent ( see, e.g ., Remington, 2020). [419] In embodiments, pharmaceutical compositions (i.e., compositions) comprising a RIMA can be administered by a variety of routes from the group consisting of intravenous, intramuscular, subcutaneous, implantable/insertable and transdermal ( see, e.g. , Kilts C.D., J. Clin. Psychiatry.2003;64 Suppl.18:31-33; and Tijani et al. J. Control Release .2022;348:970-1003). In embodiments, compositions comprising a RIMA can be administered intravenously. In embodiments, compositions comprising a RIMA can be administered intramuscularly. In embodiments, compositions comprising a RIMA can be administered subcutaneously. In embodiments, compositions comprising a RIMA can be administered using an implant/insert. In embodiments, compositions comprising a RIMA can be administered transdermally. In embodiments, compositions comprising a RIMA can be administered orally. Other routes of administration will be known. [420] In embodiments, pharmaceutical compositions comprising a disclosed second agent (e.g., antihyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antidepressant, and antihypertensive agent) can be administered by a variety of routes from the group consisting of intravenous, intramuscular, subcutaneous, implantable/insertable, transdermal, and oral. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered intravenously. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered intramuscularly. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered subcutaneously. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered using an implant/insert. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered transdermally. In embodiments, pharmaceutical compositions comprising a disclosed second agent can be administered orally. [421] Disclosed agents and compositions are in some embodiments formulated in a unit dosage form, each dosage containing a therapeutically effective amount of the agent(s), for example in the dosage amounts disclosed below. The term “unit dosage form” may refer to a physically discrete unit suited as unitary dosages for the subject to be treated, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect(s), in association with a suitable pharmaceutical carrier, 2023-12-14 diluent, or excipient. Unit dosage forms are often used for ease of administration and uniformity of dosage. Unit dosage forms can contain a single or individual dose or unit, a sub-dose, or an appropriate fraction thereof, of the pharmaceutical composition administered. [422] Unit dosage forms include capsules, troches, cachets, lozenges, tablets, ampules and vials, which may include a composition in a freeze-dried or lyophilized state; a sterile liquid carrier, for example, can be added prior to administration or delivery in vivo via pump. Unit dosage forms also include ampules and vials with liquid compositions disposed therein. Unit dosage forms further include agents for transdermal administration, such as “patches” that contact the epidermis (including the mucosa) of a subject for an extended or brief period of time. [423] In embodiments, a disclosed composition is formulated in a pharmaceutically acceptable oral dosage form. Oral dosage forms include oral liquid dosage forms (such as tinctures, drops, emulsions, syrups, elixirs, suspensions, and solutions, and the like) and oral solid dosage forms. A disclosed pharmaceutical composition may be prepared as a formulation suitable for intramuscular, subcutaneous, intraperitoneal, or intravenous injection, comprising physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, liposomes, and sterile powders for reconstitution into sterile injectable solutions or dispersions. [424] In embodiments, a disclosed composition is formulated as an oral solid dosage form. Oral solid dosage forms may include but are not limited to, lozenges, troches, tablets, capsules, caplets, powders, pellets, multiparticulates, beads, spheres, and/or any combinations thereof. Oral solid dosage forms may be formulated as immediate release, controlled release, sustained release, extended release, or modified release formulations. Accordingly, in some embodiments, the disclosed oral solid dosage forms may be in the form of a tablet (including a suspension tablet, a fast-melt tablet, a bite-disintegration tablet, a rapid-disintegration tablet, an effervescent tablet, or a caplet), a pill, a powder (including a sterile packaged powder, a dispensable powder, or an effervescent powder), a capsule (including both soft or hard capsules, e.g., capsules made from animal-derived gelatin or plant-derived HPMC, or “sprinkle capsules”), solid dispersion, solid solution, bioerodible dosage form, controlled release formulations, pulsatile or continuous release dosage forms, multiparticulate dosage forms, pellets, granules, or an aerosol. In other embodiments, the pharmaceutical formulation is in the form of a powder. In still other embodiments, the pharmaceutical formulation is in the form of a tablet, including a fast-melt tablet. Additionally, pharmaceutical formulations may be administered as a single capsule or in multiple capsule dosage form. In embodiments, the pharmaceutical formulation is administered in two, three, four, or more capsules or tablets. [425] Oral solid dosage forms may contain pharmaceutically acceptable excipients such as fillers, diluents, lubricants, surfactants, glidants, binders, dispersing agents, suspending agents, disintegrants, viscosity-increasing agents, film-forming agents, granulation aid, flavoring agents, sweetener, coating agents, solubilizing agents, and combinations thereof. Oral solid dosage forms also can comprise one or more 2023-12-14 pharmaceutically acceptable additives such as a compatible carrier, complexing agent, ionic dispersion modulator, disintegrating agent, surfactant, lubricant, colorant, moistening agent, plasticizer, stabilizer, penetration enhancer, wetting agent, anti-foaming agent, alone or in combination, as well as supplementary active agent(s). For example, a tablet may comprise an inner component covered by an outer component. In embodiments, the tablets, pills, etc. of a disclosed composition or formulation can be coated or compounded to provide a dosage form for site specific drug delivery, affording the advantage of prolonged action. For example, the two components can be separated by an enteric layer that serves to resist disintegration and permits the inner component to pass through the stomach intactly or to be delayed in release. Embodiments also include a solid preformulation containing a homogeneous mixture of first agent (e.g., a RIMA) and second agent (e.g., a antihyperglycemic agent, antidepressant, anxiolytic agent, antioxidant, anti-hypertensive agent and anti-inflammatory agent) of the present disclosure. A solid preformulation composition may be subdivided into unit dosage forms of a type described herein. [426] Supplementary active agents include preservatives, antioxidants, antimicrobial agents including biocides and biostats such as antibacterial, antiviral and antifungal agents. Preservatives can be used to inhibit microbial growth or increase stability of the active ingredient thereby prolonging the shelf life of the formulation. Suitable preservatives are known in the art and include EDTA, EGTA, benzalkonium chloride or benzoic acid or benzoates, such as sodium benzoate. Antioxidants include vitamin A, vitamin C (ascorbic acid), vitamin E, tocopherols, other vitamins or provitamins, and agents such as alpha lipoic acid. [427] In embodiments, a pharmaceutical composition comprises a disclosed first agent. In embodiments, the first agent is a RIMA. In embodiments, the RIMA is formulated in a unit dosage form. In embodiments, the RIMA is formulated as a multi-unit particulate system (MUPS). In embodiments, the RIMA is formulated as a tablet. In embodiments, the RIMA is formulated as a troche. In embodiments, the RIMA is formulated as a lozenge. In embodiments, the RIMA is formulated as a dispersible powder or granule. In embodiments, the RIMA is formulated as a hard capsule. In embodiments, the RIMA is formulated as a soft capsule. In embodiments, the RIMA is formulated as a powder. In embodiments, the RIMA is formulated as a sustained release formulation. In embodiments, the RIMA is formulated as a microcapsule. [428] In embodiments, a pharmaceutical composition comprises a disclosed second agent. In embodiments, the second agent is an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, and an antihypertensive agent. In embodiments, the second agent is formulated in a unit dosage form. In embodiments, the second agent is formulated as a multi-unit particulate system (MUPS). In embodiments, the RIMA is formulated as a tablet. In embodiments, the second agent is formulated as a troche. In embodiments, the second agent is formulated as a lozenge. In embodiments, the second agent is formulated as a dispersible powder or granule. In embodiments, the second agent is formulated as a hard capsule. In embodiments, the second agent is formulated as a soft capsule. In embodiments, the second agent is formulated as a powder. In embodiments, the second agent is formulated 2023-12-14 as a sustained release formulation. In embodiments, the second agent is formulated as a microcapsule. For example, in embodiments, metformin may be formulated as an extended-release formulation. [429] In some embodiments, a disclosed composition is formulated as an oral liquid dosage form. Oral liquid dosage forms include tinctures, drops, emulsions, syrups, elixirs, suspensions, and solutions, and the like. These oral liquid dosage forms may be formulated with any pharmaceutically acceptable excipient known to those of skill in the art for the preparation of liquid dosage forms, and with solvents, diluents, carriers, excipients, and the like chosen as appropriate to the solubility and other properties of the active agents and other ingredients. Solvents may be, for example, water, glycerin, simple syrup, alcohol, medium chain triglycerides (MCT), and combinations thereof. [430] Liquid dosage forms for oral administration may be in the form of pharmaceutically acceptable emulsions, syrups, elixirs, suspensions, and solutions, which may contain an inactive diluent, such as water. Pharmaceutical formulations may be prepared as liquid suspensions or solutions using a sterile liquid, such as but not limited to, an oil, water, an alcohol, and combinations of these pharmaceutically suitable surfactants, suspending agents, emulsifying agents, may be added for oral or parenteral administration. Liquid formulations also may be prepared as single dose or multi-dose beverages. Suspensions may include oils. Such oils include peanut oil, sesame oil, cottonseed oil, corn oil, and olive oil. Suitable oils also include carrier oils such as MCT and long chain triglyceride (LCT) oils. Suspension preparation may also contain esters of fatty acids such as ethyl oleate, isopropyl myristate, fatty acid glycerides, and acetylated fatty acid glycerides. Suspension formulations may include alcohols, (such as ethanol, isopropyl alcohol, hexadecyl alcohol), glycerol, and propylene glycol. Ethers, such as poly(ethylene glycol), petroleum hydrocarbons such as mineral oil and petrolatum, and water may also be used in suspension formulations. Suspension can thus include an aqueous liquid or a non-aqueous liquid, an oil-in-water liquid emulsion, or a water-in-oil emulsion. [431] In some embodiments, formulations are provided comprising the disclosed compositions and at least one dispersing agent or suspending agent for oral administration to a subject. The formulation may be a powder and/or granules for suspension, and upon admixture with water, a substantially uniform suspension is obtained. The aqueous dispersion can comprise amorphous and non-amorphous particles consisting of multiple effective particle sizes such that a drug is absorbed in a controlled manner over time. [432] Dosage forms for oral administration can be aqueous suspensions including pharmaceutically acceptable aqueous oral dispersions, emulsions, solutions, and syrups ( see, e.g. , Singh et al., Encyclopedia of Pharm. Tech ., 2nd Ed., 754-757 (2002)). In addition to the disclosed agents, the liquid dosage forms may comprise additives, such as one or more (a) disintegrating agents, (b) dispersing agents, (c) wetting agents, (d) preservatives, (e) viscosity enhancing agents, (f) sweetening agents, or (g) flavoring agents. [433] Disclosed compositions also may be prepared as formulations suitable for intramuscular, subcutaneous, intraperitoneal, or intravenous injection, comprising physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, liposomes, and sterile powders for 2023-12-14 reconstitution into sterile injectable solutions or dispersions. [434] Examples of suitable aqueous and non-aqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols, suitable mixtures thereof, vegetable oils, and injectable organic esters such as ethyl oleate. Additionally, the disclosed compositions can be dissolved at concentrations of >1 mg/ml using water-soluble beta cyclodextrins (e.g., beta-sulfobutyl-cyclodextrin and 2-hydroxypropyl-betacyclodextrin. Proper fluidity can be maintained, for example, by the use of a coating such as a lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. [435] Formulations suitable for subcutaneous injection also may contain additives such as preserving, wetting, emulsifying, and dispensing agents. Prevention of the growth of microorganisms can be ensured by various antibacterial and antifungal agents, such as parabens, benzoic acid, benzyl alcohol, chlorobutanol, phenol, and sorbic acid. Isotonic agents, such as sugars and sodium chloride may be used. Prolonged drug absorption of an injectable form can be brought about by use of agents delaying absorption, e.g., aluminum monostearate or gelatin. [436] Disclosed compositions also may be prepared as suspension formulations designed for extended-release via subcutaneous or intramuscular injection. Such formulations avoid first-pass metabolism, and lower dosages of the active agents will be necessary to maintain equivalent plasma levels when compared to oral formulations. In such formulations, the mean particle size of the active agents and the range of total particle sizes can be used to control the release of those agents by controlling the rate of dissolution in fat or muscle. The compositions also may be prepared for microinjection or injection cannula. [437] In embodiments, disclosed pharmaceutical compositions may be formulated into a topical dosage form. Topical dosage forms include transmucosal and transdermal formulations, such as aerosols, emulsions, sprays, ointments, salves, gels, pastes, lotions, liniments, oils, and creams. For such formulations, penetrants and carriers can be included in the pharmaceutical composition. Penetrants are known in the art, and include, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. For transdermal administration, carriers which may be used include Vaseline®, lanolin, PEG, alcohols, transdermal enhancers, and combinations thereof. [438] In some embodiments, pharmaceutical compositions comprising a disclosed agent can be formulated as or into any suitable dosage form, such as aqueous oral dispersions, aqueous oral suspensions, solid dosage forms including oral solid dosage forms, aerosols, controlled release formulations, fast melt formulations, effervescent formulations, self-emulsifying dispersions, solid solutions, liposomal dispersions, lyophilised formulations, tablets, capsules, pills, powders, pulsatile release formulations, multi-particulate formulations, immediate release, controlled release, sustained release, extended release, and modified release formulations, and mixed immediate release and controlled release formulations. [439] In embodiments, a pharmaceutical composition can be incorporated into a variety of formulations, e.g., pharmaceutically acceptable vehicles, for therapeutic administration. For example, in embodiments, the 2023-12-14 agents of the present disclosure can be formulated into pharmaceutical compositions by formulation with one or more pharmaceutically acceptable carriers, diluents, and/or excipients, and may be formulated into preparations in solid, semi-solid, liquid, or gaseous forms, such as tablets, capsules, powders, granules, ointments (e.g., skin creams), solutions, suppositories, injections, inhalants, and aerosols. [440] For example, conventional tableting ingredients include a binder, such as starch, corn starch, polyvinylpyrrolidone, gums, gum acacia, gelatin, cellulose derivatives, and combinations thereof; a diluent, such as microcrystalline cellulose, lactose, dibasic or tribasic calcium phosphate, saccharides confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, starch xylitol, sorbitol, talc, calcium carbonate, calcium sulphate, and combinations thereof; a lubricant, such as Mg, Al or Ca or Zn stearate, polyethylene glycol, glyceryl behenate, glyceryl monosterate, mineral oil sodium stearyl fumarate, stearic acid, hydrogenated vegetable oil, talc, hydrogenated soybean oil, stearyl alcohol, and combinations thereof; a glidant, such as magnesium trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate, calcium silicate, magnesium stearate, magnesium silicate, colloidal silicon dioxide, or silicon hydrogel, and combination thereof; a surface active agent; a wax; a disintegrating agent; a bioadhesive polymer, which includes proteins such as pectin, zein, or the likes, polysaccharides such as cellulose, dextrans, or the likes, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes, polyurethanes, polystyrene, polymers of acrylic and methacrylic esters, polylactides, polyanhydrides, polyorthoesters, and combinations thereof; a controlled release polymer, such as ethyl acrylate and methyl methacrylate copolymer dispersion individually and combinations thereof; a modified release polymer, such as cellulose derivatives vinyl pyrrolidone polymers and copolymers; alkylene oxide; and water. [441] As many formulations and dosage forms will be known to those of skill for various of the disclosed pharmaceutical agents, one of skill will appreciate how to select such formulations and dosage forms for use in a disclosed pharmaceutical combination or method, as well as how to prepare additional formulations or dosage forms of an agent, based on the general knowledge in the art and the information in this disclosure. [442] In embodiments, the disclosed agents are administered to a subject together in a single dosage form prepared by a compounding pharmacy. In embodiments, the disclosed agents are administered to a subject together in a single dosage form manufactured together (a “fixed-dose combination” or “FDC”). In embodiments, the disclosed agents are administered to a subject together in separate dosage forms as a co-packaged drug, e.g., approved for sale as a single product, but where the product is a blister pack or other pharmaceutical kit containing the different agents in separate dosage forms for co-administration. [443] The disclosed compositions are not limited to the disclosed agents, or limited to a single carrier, diluent, and/or excipient alone, but also may include additional active agents, and/or multiple carriers, diluents, and excipients. Pharmaceutical compositions thus may comprise an active agent together with one 2023-12-14 or more other active agents, such as two agents, three agents, or more than three agents, and these may be formulated together with one or more pharmaceutically-acceptable carriers, diluents, and/or excipients. V. Pharmaceutical Kits [444] In another aspect of this disclosure is provided pharmaceutical kits and kits of parts containing disclosed pharmaceutical agents or compositions, optionally together with suggested administration guidelines or prescribing information therefore, and optionally in a suitable container. Individual unit dosage forms can be included in multi-dose kits or containers. Pharmaceutical formulations also can be packaged in single or multiple unit dosage forms for uniformity of dosage and ease of administration. [445] In an exemplary pharmaceutical kit, comprising a suitable container, capsules, tablets, caplets, or other unit dosage forms are packaged in blister packs. “Blister pack” may refer to any of several types of pre-formed container, especially plastic packaging, containing separate receptacles (e.g., cavities or pockets) for single unit doses, where such separate receptacles are individually sealed and can be opened individually. Blister packs include such pharmaceutical blister packs known to those of ordinary skill, including Aclar® Rx160, Rx20e, SupRx, and UltRx 2000, 3000, 4000, and 6000 (Honeywell). Within the definition of multi-dose containers, and also often referred to as blister packs, are blister trays, blister cards, strip packs, push-through packs, and the like. Information pertaining to dosing and proper administration (if needed) may be printed onto a multi-dose kit directly (e.g., on a blister pack or other interior packaging holding the compositions or formulations of the invention). In embodiments, disclosed kits also can contain package inserts and other printed instructions (e.g., on exterior packaging) for administering the disclosed compositions and for their appropriate therapeutic use. [446] In some embodiments, a patient will have the option of using online software such as a website, or downloadable software such as a mobile application, to assist with compliance or to provide data relating to treatment. Such software can be used to, e.g., keep track of last dose taken and total doses taken, provide reminders and alerts for upcoming doses, provide feedback to discourage taking doses outside of set schedules, and allow for recording of specific subjective effects, or provide means for unstructured journaling. Such data collection can assist with individual patient compliance, can be used to improve or tailor individual patient care plans, and can be anonymized, aggregated, and analyzed, including by AI or natural language processing (NLP) means, to allow research into the effects of disclosed treatment methods. VI. Methods of Administration [447] Administration of the combinations and compositions disclosed herein in an “effective amount,” a “therapeutically effective amount,” a “therapeutically effective dose,” or a “pharmacologically effective amount,” may refer to an amount of the agents disclosed herein that are sufficient to provide the desired therapeutic effect, for example, relieving to some extent one or more of the symptoms of the disease or condition being treated . The result can be reduction and/or alleviation of the signs, symptoms or causes of a disease or disorder, or any other desired alteration of a biological system. An effective amount includes, for 2023-12-14 example, a prophylactically effective amount. The terms “effective amount,” “therapeutically effective amount,” “therapeutically effective dose,” and “pharmacologically effective amount,” are used interchangeably herein. [448] It is understood that an effective amount can vary from subject to subject, due to variation in metabolism of an agent, such as an agent described herein, of age, weight, general condition of the subject, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician. The effective amount will vary depending upon the subject and the disease condition being treated or health benefit sought, the weight and age of the subject, the severity of the disease condition or degree of health benefit sought, the manner of administration, and the like, all of which can readily be determined by one of skill. Further, pharmacogenomic (the effect of genotype on the pharmacokinetic, pharmacodynamic or efficacy profile of a therapeutic) information about a particular patient may affect dosage used. [449] As used herein, “therapeutic effect” or “therapeutic efficacy” means the responses(s) in a mammal, and preferably a human, after treatment that is judged to be desirable and beneficial. Hence, depending on the disorder to be treated, or improvement in physiological or psychological functioning sought, and depending on the particular constituent(s) in the compositions of the invention under consideration, those responses shall differ, but would be readily understood by those of skill. For example, in some embodiments, “therapeutic effect” may refer to increasing metabolic energy, increasing antioxidant production, and optimizing glucose levels, as disclosed herein. [450] In embodiments, an effective amount of an agent is administered daily, twice a day, three times a day, once every two days, once every three days, once every four days, weekly, or monthly. In embodiments, an effective amount of an agent is administered at least once per day for at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 10 weeks, 15 weeks, 16 weeks, or 20 weeks. In embodiments, an effective amount of an agent is administered once a day for at least 16 weeks. In embodiments, an effective amount of an agent is administered twice a day for at least 16 weeks. [451] In embodiments, the disclosed methods may be used alone or in combination with one or more non-pharmacological treatments. [452] In embodiments, the non-pharmacological treatment is transcranial magnetic stimulation (TMS) ( see, e.g ., Mayo Clinic. Transcranial Magnetic Stimulation . Mayoclinic.org. Nov. 27, 2018. https://www.mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625). Trans- cranial magnetic stimulation” or “TMS” may refer to a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression, obsessive-compulsive disorder (OCD), migraines, and other conditions. In embodiments, the TMS is personalized repetitive magnetic stimulation (PrTMS) ( see, e.g ., Makale et al. Brain Sci .2023;13(8):1179; and Blum et al. J Neurol Sci .2023;453:120809). [453] In embodiments, the non-pharmacological treatment is deep brain stimulation (DBS). “Deep brain stimulation” or “DBS” involves implanting electrodes within areas of the brain ( see, e.g ., Mayo Clinic. Deep 2023-12-14 brain stimulation . Mayoclinic.org.2018. https://www.mayoclinic.org/tests-procedures/deep-brain-stimulation/ about/pac-20384562). These electrodes produce electrical impulses that affect brain activity to treat certain medical conditions ( see, e.g., id ; and Blum, 2023). In embodiments, the disclosed methods may be used in combination with TMS and DBS. [454] In embodiments, the non-pharmacological treatment is the EPIC technique spinal procedure. The “EPIC technique spinal procedure” may refer to an approach in the spinal care industry that utilizes sound wave treatment technology to alter the biomechanical alignment of the craniocervical junction ( see, e.g. , Pierce et al. Am J Biomed Sci Res .2023;19(6):709-715). [455] In embodiments, the non-pharmacological treatment is H-Wave ® device stimulation. “H-Wave® device stimulation” may refer to a form of transcutaneous electrotherapy that utilizes a specific proprietary waveform to stimulate contractions in muscle fibers, resulting in increased blood flow and decreased edema ( see, e.g. , Williamson et al. J Pers Med .2021;11(11):1134; Bajaj et al. J Pers Med .2023; 13(2):336; Gupta et al. Int J Environ Res Public Health .2022;19(1):552). [456] In embodiments, the disclosed methods may be used with one or more other non-pharmacological treatments known by those of skill in the art. [457] In embodiments, a patient will participate in a method of the invention, or be administered a disclosed agent as part of such a method, if the patient meets certain specified inclusion criteria, does not meet certain specified exclusion criteria, does not meet any specified withdrawal criteria during the course of treatment, and otherwise satisfies the requirements of the particular embodiment as claimed. A. Dose and Dosage [458] In some embodiments, the first agent and the second agent are administered at a dosage that is effective to treat PFAOMC. In embodiments, the dosage of the first agent and the second agent requires adjustment, and the dosage of one or the other or both varies depending on the individual patient, and is determined by a medical professional such as a physician or a pharmacist or a clinician based on any, as examples, of the subject’s: height, weight, age, gender, severity of condition, side effects of drug administration, other concurrently administered agents, inherited enzymes affecting metabolism, diet, lifestyle, and physical condition. A medical professional will readily determine an effective dosage for the disclosed agents using techniques commonly known in the art. The determination of the appropriate dosage and/or route of administration will be within ordinary skill in view of the disclosure and general knowledge. Dosage levels thus may differ from patient to patient, for individual patients across time, and for different pharmaceutical compositions and formulations, but shall be able to be determined with ordinary skill. [459] In some embodiments, pharmaceutical compositions comprise an effective amount of a disclosed agent, such as for administration to a subject. Depending, for example, on the disorder to be treated, or the improvement in symptoms sought, and depending on the particular agent(s) in the disclosed compositions under consideration, therapeutic effects induced by a disclosed agent shall differ, but would be readily 2023-12-14 understood by those of skill, through an understanding of the disclosure and the general knowledge of the art (e.g., by reference to the diagnostic criteria or symptoms listed in the DSM-5 for the disorder. [460] Determination of appropriate dosing shall include not only the determination of single dosage amounts, but also the determination of the number and timing of doses, and the time(s) of day or time(s) preferable for administration. Dose and dosage may vary depending upon the onset, progression, severity, frequency, duration, probability of, or susceptibility of the symptom to which treatment is directed, clinical endpoint desired, previous, simultaneous or subsequent treatments, general health, age, gender, and race of the patient, bioavailability, potential adverse systemic, regional, or local side effects, the presence of other disorders or diseases in the patient, and other factors appreciated by those in the art (e.g., medical or familial history). Dose amount, frequency, or duration may be increased or reduced, as indicated by the clinical outcome desired, status of the disorder or symptoms, any adverse side effects of the treatment or therapy, or concomitant medications. Those in the art will appreciate the factors that may influence the dosage, frequency, and timing required to provide an amount sufficient or effective for providing a therapeutic effect or benefit, and to do so depending on the type of therapeutic effect desired and to avoid or minimize adverse effects. In embodiments, the dose actually administered will be determined by a physician, in light of the relevant circumstances, including the disorder to be treated, the chosen route of administration, the actual composition administered, the age, weight, and response of the individual patient, and the severity of the patient’s symptoms, and therefore any dosage ranges disclosed herein are not intended to limit the scope of the invention. In some instances, dosage levels below the lower limit of a disclosed range may be more than adequate, while in other cases doses above a range may be employed without causing any harmful side effects, provided for instance that such larger doses also may be divided into several smaller doses for administration, either taken together or separately. [461] In some embodiments, a single agent is administered to a subject. In some embodiments, an agent is administered to a subject in combination with one or more additional agents. In some embodiments, an agent is administered prior to administration of one or more additional agents. In some embodiments, an agent is administered simultaneously with one or more additional agents. In some embodiments, an agent is administered after administration of one or more additional agents. [462] In some embodiments, a RIMA, such as moclobemide is administered to a subject. In some embodiments, lorazepam is administered to a subject in combination with one or more additional agents. In some embodiments, lorazepam is administered prior to administration of one or more additional agents. In some embodiments, lorazepam is administered simultaneously with one or more additional agents. In some embodiments, lorazepam is administered after administration of one or more additional agents. [463] In some embodiments, moclobemide is not administered to a subject. In some embodiments, moclobemide is not administered to a subject in combination with one or more additional agents. In some embodiments, moclobemide is not administered prior to administration of one or more additional agents. In 2023-12-14 some embodiments, moclobemide is not administered simultaneously with one or more additional agents. In some embodiments, moclobemide is not administered after administration of one or more additional agents. [464] In some embodiments, an anxiolytic agent, such as lorazepam is administered to a subject. In some embodiments, lorazepam is administered to a subject in combination with one or more additional agents. In some embodiments, lorazepam is administered prior to administration of one or more additional agents. In some embodiments, lorazepam is administered simultaneously with one or more additional agents. In some embodiments, lorazepam is administered after administration of one or more additional agents. [465] In some embodiments, lorazepam is not administered to a subject. In some embodiments, lorazepam is not administered to a subject in combination with one or more additional agents. In some embodiments, lorazepam is not administered prior to administration of one or more additional agents. In some embodiments, lorazepam is not administered simultaneously with one or more additional agents. In some embodiments, lorazepam is not administered after administration of one or more additional agents. [466] In some embodiments, an agent is administered at least 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, or 24 hours before administration of an additional agent. In some embodiments, an agent is administered between about 1 hour and 12 hours before administration of an additional agent. In some embodiments, an agent is administered between about 2 hours and 8 hours before administration of an additional agent. In some embodiments, an agent is administered between about 3 hours and 6 hours before administration of an additional agent. In some embodiments, an agent is administered about 2 hours before administration of an additional agent. In some embodiments, an agent is administered about 4 hours before administration of an additional agent. The “additional agent” may in embodiments be the “second agent.” [467] In embodiments, administration to a subject of an effective amount of an agent “simultaneously” with treatment with an additional agent may refer to administration to a subject of an effective amount of an agent at substantially the same time as administration to the subject of treatment with an additional agent. In some embodiments, “simultaneously” may refer to administration of an agent within not more than 15 minutes, 10 minutes, preferably 5 minutes, or more preferably 1 minute of administration of an additional agent. In embodiments, an agent is administered less than 15 minutes before administration of an additional agent. In some embodiments, an agent is administered less than 10 minutes before administration of an additional agent. In some embodiments, an agent is administered less than 5 minutes before administration of an additional agent. In some embodiments, an agent is administered less than 1 minute before administration of an additional agent. [468] In some embodiments, an agent is administered at least 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, or 24 hours after administration of an additional agent. In some embodiments, an agent is administered between about 1 hour and 12 hours after administration of an additional agent. In some embodiments, an agent is administered between about 2 hours and 8 hours after administration of an additional agent. In some embodiments, an agent is administered between about 3 hours and 6 hours after 2023-12-14 administration of an additional agent. In some embodiments, an agent is administered about 2 hours after administration of an additional agent. In some embodiments, an agent is administered about 4 hours after administration of an additional agent. As will be appreciated by one of skill, the timing of administration of an agent may be selected based on the properties and release profile of the pharmaceutical composition comprising the agent. [469] In embodiments, administering to a subject an effective amount of a RIMA comprises administering the RIMA in a dose of between about 0.01 mg to about 1000 mg per unit dose (e.g., about 0.05 mg to about 950 mg per unit dose, about 50 mg to about 900 mg per unit dose, about 50 mg to about 850 mg per unit dose, about 50 mg to about 800 mg per unit dose, about 50 mg to about 750 mg per unit dose, about 50 mg to about 700 mg per unit dose, about 50 mg to about 650 mg per unit dose, about 50 mg to about 600 mg per unit dose, about 50 mg to about 550 mg per unit dose, about 50 mg to about 500 mg per unit dose, about 50 mg to about 450 mg per unit dose, about 50 mg to about 400 mg per unit dose, about 50 mg to about 350 mg per unit dose, about 50 mg to about 300 mg per unit dose, about 50 mg to about 250 mg per unit dose, about 50 mg to about 200 mg per unit dose, about 50 mg to about 150 mg per unit dose, about 50 mg to about 100 mg per unit dose). In embodiments, moclobemide is administered at a dose of, e.g., between about 150-600 mg, between about 300-600 mg, between about 300-450 mg, or between about 450-600 mg. [470] In embodiments, the disclosed second agent is an anti-hyperglycemic agent, antidepressant, anxiolytic agent, antioxidant, anti-hypertensive agent, or an anti-inflammatory agent. In embodiments, administering to the subject an effective amount of a disclosed anti-hyperglycemic agent, antidepressant, anxiolytic agent, antioxidant, anti-hypertensive agent, or anti-inflammatory agent, comprises administering the agent in a dose of between about 0.01 mg to about 1000 mg per unit dose (e.g., about 0.05 mg to about 950 mg per unit dose, about 50 mg to about 900 mg per unit dose, about 50 mg to about 850 mg per unit dose, about 50 mg to about 800 mg per unit dose, about 50 mg to about 750 mg per unit dose, about 50 mg to about 700 mg per unit dose, about 50 mg to about 650 mg per unit dose, about 50 mg to about 600 mg per unit dose, about 50 mg to about 550 mg per unit dose, about 50 mg to about 500 mg per unit dose, about 50 mg to about 450 mg per unit dose, about 50 mg to about 400 mg per unit dose, about 50 mg to about 350 mg per unit dose, about 50 mg to about 300 mg per unit dose, about 50 mg to about 250 mg per unit dose, about 50 mg to about 200 mg per unit dose, about 50 mg to about 150 mg per unit dose, about 50 mg to about 100 mg per unit dose). [471] In embodiments, a subject is administered an effective amount of an antihyperglycemic agent. In embodiments, the dose of the antihyperglycemic agent is between about 500 mg and 2500 mg. In embodiments, the dose of the antihyperglycemic agent is between about 0.001 mg and 5000 mg. In embodiments, the dose of the antihyperglycemic agent is less than or equal to about 100 mg. In embodiments, the dose of the antihyperglycemic agent is about 10 mg. In embodiments, the dose of the anti-hyperglycemic agent is about 1 mg. In embodiments, the dose of the antihyperglycemic agent is about 2023-12-14 0.1 mg. In embodiments, the dose of the anti-hyperglycemic agent is about 0.01 mg. In embodiments, the dose of the antihyperglycemic agent is about 0.001 mg. For example, in embodiments, metformin may be administered at a dose of between about 1-4000 mg, between about 1000-2000 mg, between about 500-2500 mg, or between about 450-600 mg. For example, in embodiments, repaglinide may be administered at a dose of between about 0.01-10 mg or between about 0.1-2 mg. [472] In embodiments, a subject is administered an effective amount of an antioxidant. In embodiments, the dose of the antioxidant is between about 5 mg to 10 mg. In embodiments, the dose of the antioxidant is between about 10 mg to 15 mg. In embodiments, the dose of the antioxidant is between about 15 mg to 45 mg. In embodiments, the dose of the antioxidant is between about 45 mg to 120 mg. In embodiments, the dose of the antioxidant is between about 120 mg to 250 mg. In embodiments, the dose of the antioxidant is between about 250 mg to 500 mg. In embodiments, the dose of the antioxidant is between about 500 mg to 1000 mg. In embodiments, the dose of the antioxidant is between about 1000 mg to 1500 mg. For example, in embodiments, N-acetylcysteine may be administered at a dose of 1200 mg. [473] In embodiments, a subject is administered an effective amount of an anti-inflammatory agent. In embodiments, the dose of the anti-inflammatory agent is between about 200 mg and 400 mg. In embodiments, the dose of the anti-inflammatory agent is between about 400 mg and 3200 mg. For example, in embodiments, lumiracoxib may be administered at a dose of between 200-400 mg. In embodiments, ibuprofen may be administered at a dose of between 400-3200 mg. [474] In embodiments, a subject is administered an effective amount of an anxiolytic agent. In embodiments, the dose of the anxiolytic agent is between about 0.1 mg to 1 mg. In embodiments, the dose of the anxiolytic agent is between about 1 mg to 15 mg. In embodiments, the dose of the anxiolytic agent is between about 15 mg to 60 mg. In embodiments, the dose of the anxiolytic agent is between about 60 mg and 80 mg. In embodiments, the dose of the anxiolytic agent is between about 50 mg to 100 mg. In embodiments, the dose of the anxiolytic agent is between about 100 mg to 200 mg. In embodiments, the dose of the anxiolytic agent is between about 200 mg to 300 mg. In embodiments, the dose of the anxiolytic agent is between about 300 mg to 600 mg. In embodiments, the dose of the anxiolytic agent is between about 900 mg to 2000 mg. In embodiments, the dose of the anxiolytic agent is between about 2000 mg to 2400 mg. In embodiments, propranolol may be administered at a dose of between about 40-640 mg. In embodiments, zolpidem may be administered at a dose of 10 mg. In embodiments, zaleplon may be administered at a dose of 20 mg. [475] In embodiments, a subject is administered an effective amount of an antidepressant. In embodiments, the dose of the antidepressant is between about 75 mg and 150 mg. In embodiments, the dose of the antidepressant is between about 0.01 mg to 4000 mg. In embodiments, the dose of the antidepressant is less than or equal to about 2000 mg. In embodiments, the dose of the antidepressant is about 1000 mg. In embodiments, the dose of the antidepressant is about 600 mg. In embodiments, the dose 2023-12-14 of the antidepressant is about 500 mg. In embodiments, the dose of the antidepressant is about 100 mg. In embodiments, the dose of the antidepressant is about 50 mg. In embodiments, the dose of the antidepressant is about 10 mg. In embodiments, the dose of the antidepressant is about 5 mg. In embodiments, the dose of the antidepressant is about 0.5 mg. For example, in embodiments, sertraline may be administered at a dose of between about 25-300 mg or between about 50-200 mg. In embodiments, solriamfetol may be administered at a dose of between 75-150 mg. In embodiments, modafinil may be administered at a dose of between 200-400 mg. [476] In embodiments, a subject is administered an effective amount of an antidepressant, wherein the antidepressant is a cognitive enhancer. In embodiments, the dose of the cognitive enhancer is between about 200 mg and 400 mg. For example, in embodiments, vitamin D (e.g., vitamin D ₃ ) may be administered at a dose of about 125 mg. [477] In embodiments, a subject is administered an effective amount of an anti-hypertensive agent. In embodiments, the dose of the anti-hypertensive agent is between about 60 mg and 360 mg. For example, in embodiments, nimodipine may be administered at a dose of between about 60-360 mg. [478] In embodiments, the ratio of amount of the first agent, such as the RIMA, and the second agent (or the ratio of the second to the first agent) administered to a subject may be at most 1:1, 1:10, 1:100, 1:1,000, 1:10,000, 1:100,000, 1:1,000,000, 1:10,000,000, 1:100,000,000, or 1:1,000,000,000. The two agents may be administered concomitantly, either in the same or different formulations, or at different times. The two agents may be administered simultaneously, separately, or sequentially. [479] In general, the disclosed methods will be appreciated to work for any subject, although individual variation is to be expected, and will be appreciated in view of the disclosure and ordinary skill. Where there is variation between individuals, modification to the disclosed combinations, compositions, and methods will be understood based on the teachings herein in combination with general knowledge in the art. In some instances, certain personalized or precision medicine approaches may be utilized, based on individual characteristics, including variations in drug metabolism (e.g., related to the metabolism of any one or more agents in a combination), genetics, or immune system (e.g., differences for immunocompromised subjects). Dosage levels, including starting and maintenance dosages if different, thus may differ from patient to patient, for individual patients across time, and for different pharmaceutical agents and compositions, but shall be able to be determined with ordinary skill. B. Treatment Methods [480] In some aspects are disclosed methods of treating a subject with PFAOMC. In embodiments, disclosed methods are useful to treat PFAOMC in the subject, i.e., to treat a psychological or behavioral factor affecting the other medical condition. Treating PFAOMC and treating “a psychological or behavioral factor” will be understood to include treating one or more psychological or behavioral factors affecting the other medical condition, and therefore may include treating more than a single psychological or behavioral 2023-12-14 factor, such as treating two psychological or behavioral factors, treating three psychological or behavioral factors, treating four psychological or behavioral factors, treating five psychological or behavioral factors, or treating greater than five psychological or behavioral factors. [481] In some embodiments, disclosed methods are useful to treat PFAOMC and the other medical condition in the subject, i.e., to treat a psychological or behavioral factor affecting the other medical condition as well as the other medical condition itself. [482] In some embodiments, disclosed methods are useful to treat a medical condition in a subject, where the medical condition is affected by a psychological or behavioral factor. In embodiments, disclosed methods treat the medical condition and the psychological or behavioral factor that affects it. [483] In some aspects are disclosed methods of administering a subject a RIMA, such as moclobemide. In embodiments, administering a subject a RIMA, such as moclobemide, is useful to treat PFAOMC in the subject. In embodiments, administering a subject a RIMA, such as moclobemide, is useful to treat PFAOMC and the other medical condition in a subject. In embodiments, administering a subject a RIMA, such as moclobemide, is useful to a medical condition in a subject, where the medical condition is affected by a psychological or behavioral factor, and is also useful to treat the psychological or behavioral factor. [484] In some aspects are disclosed methods of administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent. In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, is useful to treat PFAOMC in the subject. In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, is useful to treat PFAOMC and the other medical condition in the subject . [485] In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, is useful to a medical condition in a subject, where the medical condition is affected by a psychological or behavioral factor, and is also useful to treat the psychological or behavioral factor. [486] In some aspects are disclosed methods of administering a subject a RIMA, such as moclobemide, and an additional active agent. In embodiments, the additional active agent is an amino acid, antioxidant, anti-inflammatory agent, analgesic, antineuropathic or antinociceptive agent, antimigraine agent, anxiolytic, antidepressant, antipsychotic, anti-PTSD agent, cannabinoid, dissociative, immunostimulant, anti-cancer agent, antiemetic, orexigenic, antiulcer agent, anticholinergic agent, anti-ischemic agent, antihistamine (e.g., 2023-12-14 diphenhydramine, meclizine, promethazine, dimenhydrinate) , antihypertensive, antimigraine agent, anticonvulsant, antiepileptic, bronchodilator, mood stabilizer, neuroprotectant, serotonergic agent, neuroactive agent, entactogen or empathogen, entheogen, psychedelic, monoamine oxidase inhibitor (MAOI), tryptamine, terpene, phenethylamine, sedative, serotonergic agent, stimulant, opioid modulator, N-methyl-D-aspartate (NMDA) receptor agent, vitamin, SSRI, SNRI, NRI, NDRI, TCA, benzodiazepine, or a phosphodiesterase inhibitor (e.g., a PDE-1 inhibitor, a PDE-2 inhibitor, a PDE-3 inhibitor, a PDE-4 inhibitor such as apremilast, or a PDE-5 inhibitor). [487] In embodiments, administering a subject a RIMA, such as moclobemide, and an additional active agent, is useful to treat PFAOMC in the subject. In embodiments, administering a subject a RIMA, such as moclobemide, and an additional active agent, is useful to treat PFAOMC and the other medical condition in the subject. In embodiments, administering a subject a RIMA, such as moclobemide, and an additional active agent, is useful to a medical condition in a subject, where the medical condition is affected by a psychological or behavioral factor, and is also useful to treat the psychological or behavioral factor. [488] In some aspects are disclosed methods of administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, further together with and an additional active agent. In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, further together with and an additional active agent, is useful to treat PFAOMC in the subject. In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, further together with and an additional active agent, is useful to treat PFAOMC and the other medical condition in the subject . [489] In embodiments, administering a subject a RIMA, such as moclobemide, together with a second pharmaceutical agent, such as an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, or an antihypertensive agent, further together with and an additional active agent, is useful to a medical condition in a subject, where the medical condition is affected by a psychological or behavioral factor, and is also useful to treat the psychological or behavioral factor. VII. Examples [490] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention, which shall be known by reference to the complete disclosure and appended claims. EXAMPLE 1: Combination Therapy with a RIMA and an Antihyperglycemic Agent to Treat PFAOMC [491] A study is conducted in subjects to determine the efficacy of using a RIMA in combination with an antihyperglycemic agent for the treatment of PFAOMC. For purposes of this study, PFAOMC are 2023-12-14 characterized by the occurrence of one or more of the following during the same 2-week period, including symptoms of depression, anxiety or obsessive-compulsive disorder, along with dysfunctional patterns of interpersonal interaction, impaired coping styles, distress and maladaptive health behaviors (e.g., denial of symptoms, poor adherence to medical recommendations, or medication nonadherence), and wherein the medical condition is prediabetes. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning, and the episode must not be attributable to the psychological effects of a substance or another medical condition. [492] A subject is diagnosed with prediabetes if they exhibit one of the following factors: (1) a HbA1c concentration ranging from between about 5.7% to 6.4%; (2) FPG levels ranging from between about 100 to 125 mg/dl; or (3) a two-hour plasma glucose concentration ranging from between about 140 to 199 mg/dl, measured using an oral glucose tolerance test (oGTT). [493] Selection Criteria : Each subject candidate undergoes a clinical interview, a SCID-5, and a physical exam to ascertain the presence of both a psychological disorder and a medical condition. A subject’s general state of health is assessed using the Cornell Medical Index Health Questionnaire and via analyses of urine and blood samples. [494] The following psychometric instruments are used to evaluate a subject’s psychological state: the BDI, the HAM-D, the HAM-A, the STAI, the DSI, the PSS-10, the POMS questionnaire, the YFAS, the EDE-Q, the FCI, the Addiction Severity Index, the Yale-Brown Obsessive-Compulsive Scale, the FCQs, the TFRQ-R18, the RPQ , the TAPQ , the RDSQ-29, the GARS Test , the CAPS , and the Civilian M-PTSD Scale . [495] Prediabetes is diagnosed via administration to a subject of a blood test following a 12-hour fasting period, such as a HbA1c test, and/or examining of results obtained via an oral glucose tolerance test (oGTT). [496] Exclusion Criteria : Subjects having conditions such as pregnancy, dementia, bipolar disorder, schizophrenia spectrum disorder, major depression disorder, drug/alcohol use disorder, an eating disorder, endocrinopathy, chronic obstructive pulmonary disease, congestive heart failure, hepatitis, hepatic failure, cirrhosis, HIV positive status, end-stage kidney disease, or neurological conditions (e.g., seizure disorder, head trauma, past brain surgery, multiple sclerosis, or Parkinson's disease) are excluded from the study. Subjects using dopamine/opioid antagonists or agonists, or subjects using drugs with prominent orexigenic or anorexigenic effects (e.g., psychostimulants, antihistamines, cannabinoids, dopaminergic or antidopaminergic agents, mood stabilizers, and antidepressants with prominent catecholaminergic effects such as tricyclics, bupropion, mirtazapine, venlafaxine, and duloxetine) within the past month are also excluded from the study. Urine toxicology screens/breathalyzer tests are used to rule out subjects with recent drug and alcohol consumption. [497] Administration of drugs : Subjects who meet the selection criteria and are not excluded are randomly separated into three groups of twenty. These three groups are matched based on the nature of the psychological symptom(s) (e.g., depressive-, anxiety- or obsessive-compulsive) and medical condition(s) 2023-12-14 (e.g., baseline HbA1c percentage, FPG or 2h oGTT plasma glucose concentration) experienced by subjects, demographics, baseline anthropomorphic and psychometric variables, the educational levels of subjects, and proportions of ethnic minorities. [498] Group 1 consists of subjects experiencing PFAOMC, wherein the other medical condition is prediabetes. Subjects assigned to Group 1 are treated with a combination of a RIMA and an antihyperglycemic agent. The RIMA to be used in this study is moclobemide, and the antihyperglycemic agent to be used is metformin. Group 2 consists of subjects experiencing PFAOMC, wherein the other medical condition is prediabetes. Subjects assigned to Group 2 are only treated with an antihyperglycemic agent. The antihyperglycemic agent to be used is metformin. Group 3 consists of subjects experiencing PFAOMC, wherein the other medical condition is prediabetes. Subjects assigned to Group 3 are only treated with a RIMA. The RIMA to be used is moclobemide. [499] Before treatment, baseline PFAOMC symptoms are evaluated using the above described psychodiagnostic and psychometric tools. Baseline glucoregulatory indices are measured by conducting a fasting blood work up and oGTT. Subjects are treated according to their group treatment plan for 16 weeks. Group 1 is administered 150 mg of moclobemide orally twice a day and 1000 mg of metformin orally, once daily at bedtime. Group 2 is administered 1000 mg of metformin orally, once daily at bedtime. Group 3 is administered 150 mg of moclobemide orally twice a day. The dosage of moclobemide used may be optionally increased to 600 mg daily in divided doses if tolerated by the subject. The dosage of metformin can be optionally increased up to 2500 daily in divided doses if tolerated by the subject. In the course of 16 weeks subjects are evaluated using the above described psychodiagnostic and psychometric tools. A blood workup as described above, including an oGTT, is performed at baseline, at Week 8 and at Week 16. Improvements in PFAOMC are measured by a decrease in the number and duration of symptoms elicited using the psychodiagnostic and psychometric tools. Improvements in prediabetes are measured by glucoregulatory indices derived from the blood work as described above. The primary outcome measure is based on measures of glucoregulatory function (e.g., FPG, HOMA-IR, and the Matsuda Index) at 16 weeks. (Taveira, et al., J. Psychopharmacol . 2014;28(4):395-400; Elman, et al., Hum . Psychopharmacol . 2017;32(4)). Secondary measures are based on body mass index (BMI), body fat and fat-free mass, along with analyses of plasma lipids and liver function tests in subjects. [500] All analyses are performed on an intention-to-treat basis. “Intention-to-treat analysis” may refer to a method for analyzing results in a prospective randomized study where all subjects who are randomized are included in the statistical analysis and analyzed according to the group they were originally assigned, regardless of what treatment (if any) they received ( see, e.g ., McCoy CE. , West J. Emerg. Med. 2017;18(6):1075-1078.) Time-related clinical outcomes are analyzed by means of generalized estimating equations (GEEs) using a Gaussian link function and an exchangeable correlation structure to account for repeated measures with subjects over time and adjust for potential imbalances in baseline risk factors. 2023-12-14 “Generalized estimating equations” (GEEs) refer to a set of equations that are solved to obtain parameter estimates (e.g., model coefficients), and are often used for modeling longitudinal or clustered data ( see, e.g ., Ballinger et. al. Organizational Research Methods .2004;7(2):127-150). [501] When the group (Metformin vs. Metformin + Moclobemide vs. Moclobemide) by time (Week 0, 1, 3, 5, 7, 10 ,13 and 16) interaction is significant, post-hoc Wald tests are conducted to determine if, and at what time points, the change from the baseline is significant. [502] “Post hoc Wald test” may refer to a parametric, statistical measure used to confirm whether a set of independent variables are collectively 'significant' for a model. A post-hoc Wald test allows the user to select which estimates are included in the test. In a complex sample, the variance is estimated as a stratified, between-PSU variance. Therefore, the total degrees of freedom for the variance estimate equals the number of clusters less the number of strata. Sensitivity analysis on the primary outcome is conducted by imputing missing data with a conservative last observation carried forward approach. [503] Demographic variables are assessed with Student’s t-tests or Fisher’s exact tests as appropriate. “Fisher's exact test” may refer to a statistical significance test used to determine if there are nonrandom associations between two categorical variables. “Student’s t-test” may refer to a statistical method of testing hypotheses about the mean of a small sample drawn from a normally distributed population when the standard deviation of the population is unknown. Data is analyzed using Statistica (StatSoft, Inc., Tulsa, OK). All analyses are two-tailed, and significance is defined as p<0.05. [504] It is expected that subjects in Group 1 will exhibit more rapid recovery in PFAOMC as well as in glucoregulatory indices than subjects in Group 2 and 3. It is expected that the subjects in Group 1 treated with the combination of a RIMA (e.g., moclobemide) and an antihyperglycemic agent (e.g., metformin) will show statistically significant improvement in the outcomes when compared to those subjects who are treated with moclobemide or metformin alone. EXAMPLE 2: Combination Therapy with a RIMA and an Antihypertensive Agent to Treat PFAOMC [505] A study is conducted in subjects to determine the efficacy of using a RIMA in combination with an anti-hypertensive agent for the treatment of PFAOMC. For purposes of this study, PFAOMC are characterized by the occurrence of one or more symptoms as described in Example 1, and wherein the medical condition is hypertension. [506] A subject is diagnosed with hypertension if the subject exhibits a systolic pressure greater than 140 mmHg and/or a diastolic pressure greater than 90 mmHg. [507] The presence of PFAOMC in a subject is characterized by the occurrence of one or more symptoms as discussed in Example 1. [508] Administration of drugs : Subjects who meet the selection criterion, and are not excluded by the exclusion criterion as shown in Example 1 are randomly assigned into three groups of twenty each. These three groups are matched based on the nature of the psychological symptom(s) (e.g., depressive-, anxiety- 2023-12-14 or obsessive-compulsive) and medical condition(s) (e.g., systolic blood pressure, diastolic blood pressure, BMI) experienced by subjects, demographics, baseline anthropomorphic and psychometric variables, the educational levels of subjects, and proportions of ethnic minorities. [509] Group 1 consists of subjects experiencing PFAOMC, wherein the other medical condition is hypertension. Subjects assigned to Group 1 are treated with a combination of a RIMA and an anti-hypertensive agent. The RIMA to be used in this study is to be moclobemide, and the anti-hypertensive agent to be used is propranolol. Group 2 consists of subjects experiencing PFAOMC, wherein the other medical condition is hypertension. Subjects in Group 2 are only treated with an antihypertensive agent. The anti-hypertensive agent to be used is propranolol. Group 3 consists of subjects experiencing PFAOMC, wherein the other medical condition is hypertension. Subjects assigned to Group 3 are only treated with a RIMA. The RIMA to be used is moclobemide. [510] Before treatment, baseline PFAOMC symptoms are evaluated using the above described psychodiagnostic and psychometric tools. Effects on hypertension are measured via blood pressure and BMI analyses. Subjects are treated according to their group treatment plan for 16 weeks. Group 1 is administered 150 mg of moclobemide and 40 mg of propranolol, orally twice a day. Group 2 is administered 40 mg of propranolol orally twice a day. Group 3 is administered 150 mg of moclobemide orally twice a day. In the course of 16 weeks participants are evaluated using the above described psychodiagnostic and psychometric tools. Improvements in PFAOMC are measured by a decrease in the number and duration of symptoms elicited using the psychodiagnostic and psychometric tools. Blood pressure and heart rate are measured frequently in subjects as a primary outcome measure. Secondary measures are based on results obtained via psychodiagnostic and psychometric tools. [511] All analyses are performed on an intention-to-treat basis. Time-related clinical outcomes are analyzed by means of GEEs using a Gaussian link function and an exchangeable correlation structure to account for repeated measures with subjects over time and adjust for potential imbalances in baseline risk factors. When the group (Propranolol vs. Propranolol + Moclobemide vs. Moclobemide) by time (Week 0, 1, 3, 5, 7, 10 ,13 and 16) interaction is significant, post-hoc Wald tests are conducted to determine if, and at what time points, the change from the baseline is significant. Sensitivity analysis on the primary outcome is conducted by imputing missing data with a conservative last observation carried forward approach. Demographic variables are assessed with Student’s t-tests or Fisher’s exact tests as appropriate. Data is analyzed using Statistica (StatSoft, Inc., Tulsa, OK). All analyses are two-tailed, and significance is defined as p<0.05. [512] It is expected that subjects in Group 1 will exhibit more rapid recovery in PFAOMC as well as hemodynamic indices than subjects in Group 2 and 3. It is expected that the subjects in Group 1 treated with the combination of a RIMA (e.g., moclobemide) and an antihypertensive agent (e.g., propranolol) will show statistically significant improvement in the outcomes when compared to those subjects who are treated with 2023-12-14 propranolol or moclobemide alone. EXAMPLE 3: Combination Therapy with a RIMA and an Anti-Inflammatory Agent to Treat PFAOMC [513] A study is conducted in subjects to determine the efficacy of using a RIMA in combination with an anti-inflammatory agent for the treatment of PFAOMC. For purposes of this study, PFAOMC are characterized by the occurrence of one or more symptoms as described in Example 1, and wherein the medical condition is an inflammatory disorder. [514] A subject is diagnosed with an inflammatory disorder if the subject has an elevated erythrocyte sedimentation rate (ESR), or increased levels of C-reactive proteins (CRPs) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. [515] The presence of PFAOMC in a subject is characterized by the occurrence of one or more symptoms as discussed in Example 1. [516] Administration of drugs : Subjects who meet the selection criterion, and are not excluded by the exclusion criterion as shown in Example 1 are randomly assigned into three groups of twenty each. These three groups are matched based on the nature of the psychological symptom(s) (e.g., depressive-, anxiety- or obsessive-compulsive) and medical condition(s) (e.g., levels of ESR, CRP, IL-6, IL-1, anti-CCP) experienced by subjects, demographics, baseline anthropomorphic and psychometric variables, the educational levels of subjects, and proportions of ethnic minorities. [517] Group 1 consists of subjects experiencing PFAOMC, wherein the other medical condition is excessive inflammation (e.g., rheumatoid arthritis). Subjects assigned to Group 1 are treated with a combination of a RIMA and an anti-inflammatory agent. The RIMA to be used in this study is moclobemide, and the anti-inflammatory agent to be used is ibuprofen. Group 2 consists of subjects experiencing PFAOMC, wherein the other medical condition is excessive inflammation. Subjects assigned to Group 2 are only treated with an anti-inflammatory agent. The anti-inflammatory agent to be used is ibuprofen. Group 3 consists of subjects experiencing PFAOMC, wherein the other medical condition is excessive inflammation. Subjects assigned to Group 3 are only treated with a RIMA. The RIMA to be used is moclobemide. [518] Before treatment, baseline PFAOMC symptoms are evaluated using the above described psychodiagnostic and psychometric tools. Effects on inflammation are measured via anti-inflammatory markers found in plasma, such as ESR, CRP, IL-6, IL-1, and anti-CCP. Subjects are treated according to their group treatment plan for 16 weeks. Group 1 is administered 150 mg of moclobemide, orally twice a day, and 800 mg of ibuprofen, orally three times a day. Group 2 is administered 800 mg of ibuprofen, orally three times a day. Group 3 is administered 150 mg of moclobemide orally twice a day. In the course of 16 weeks subjects are evaluated using the above described psychodiagnostic and psychometric tools. Improvements in PFAOMC are measured by a decrease in the number and duration of symptoms elicited using the psychodiagnostic and psychometric tools. Concentrations of the above-described anti-inflammatory markers found in the plasma of subjects are used as primary outcome measures. Secondary measures are based on 2023-12-14 results obtained via psychodiagnostic and psychometric tools and the Brief Pain Questionnaire ( see, e.g ., Elman, et al., Transl. Psychiatry .2018;8(1):240). [519] All analyses are performed on an intention-to-treat basis. Time-related clinical outcomes are analyzed by means of GEEs using a Gaussian link function and an exchangeable correlation structure to account for repeated measures with participants over time and adjust for potential imbalances in baseline risk factors. When the group (Ibuprofen vs. Ibuprofen + Moclobemide vs. Moclobemide) by time (Week 0, 1, 3, 5, 7, 10 ,13 and 16) interaction is significant, post-hoc Wald tests are conducted to determine if, and at what time points, the change from the baseline is significant. Sensitivity analysis on the primary outcome is conducted by imputing missing data with a conservative last observation carried forward approach. Demographic variables are assessed with Student’s t-tests or Fisher’s exact tests as appropriate. Data is analyzed using Statistica (StatSoft, Inc., Tulsa, OK). All analyses are two-tailed, and significance is defined as p<0.05. [520] It is expected that subjects in Group 1 will exhibit more rapid recovery in PFAOMC as well as in inflammatory indices than participants in Group 2 and 3. It is expected that the subjects in Group 1 treated with the combination of a RIMA (e.g., moclobemide) and an anti-inflammatory agent (e.g., ibuprofen) will show statistically significant improvement in the outcomes when compared to those subjects who are treated with moclobemide or ibuprofen alone. EXAMPLE 4: Exemplary Clinical Protocols for Subjects with PFAOMC [521] Patient 1 : Patient 1 is diagnosed with prediabetes after exhibiting a HbA1c concentration of about 5.9% following administration of a blood test. Patient 1 begins to experience increased fatigue. Patient 1 attends a follow-up visit with their healthcare professional. Patient 1 completes the SCID-5 and POMS questionnaire to determine the presence of psychological factors affecting the prediabetes observed at baseline and to rule out other psychiatric problems. Patient 1 obtains a high score in connection with the “fatigue” state based on the questionnaire. It is determined that the increased fatigue experienced by Patient 1 exacerbates the course of prediabetes, as Patient 1 is too fatigued to engage in daily physical exercise. Patient 1 is diagnosed with PFAOMC. Patient 1 is administered a RIMA, such as 150 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 1 is also administered an antihyperglycemic agent, such as 500-1000 mg of metformin up to twice a day for 16 weeks. Following the 16-week period, Patient 1 again completes a form implementing the POMS questionnaire. Patient 1 is expected to exhibit more positive emotions and show improvement in psychological factors affecting prediabetes in comparison with baseline levels. Patient 1 shows an improvement in PFAOMC. Patient 1 also exhibits improved FPG concentrations by participating in daily physical exercise and taking medicines as prescribed by their healthcare professional. Patient 1 is also expected to experience enhanced insulin sensitivity in conjunction with decreased gluconeogenesis in the liver and improved affective states caused by synergistic effects induced by the combination therapy. 2023-12-14 [522] Patient 2 : Patient 2 is diagnosed with hypertension after exhibiting a systolic blood pressure of 160 mmHg. Patient 2 begins to experience two depressive symptoms in a period of 2 weeks. Patient 2 attends a follow-up visit with their healthcare professional. Patient 2 completes the SCID-5 and the BDI to determine the presence of any psychological factors affecting the hypertension observed at baseline. Patient 2 obtains a score of 14 on the BDI, which is correlated with symptoms of mild depression. It is determined that the depressive symptoms experienced by Patient 2 interfere with the course of hypertension driving consumption of unhealthy diet high in sodium. However, a diagnosis of a depressive disorder is not warranted as Patient 2 does not experience five or more symptoms of depression during a 2-week period. Patient 2 is diagnosed with PFAOMC. Patient 2 is administered a RIMA, such as 300 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 2 is also administered an antihypertensive agent, such as 60 mg of nimodipine three times a day for 16 weeks. After the 16-week period, Patient 2 again completes a form implementing the BDI. Patient 2 is expected to exhibit improvement in depressive symptoms and in psychological factors affecting hypertension in comparison with baseline levels. Patient 2 shows an improvement in PFAOMC. Patient 2 also exhibits improvement in systolic blood pressure by adopting a healthier diet as prescribed by their healthcare professional. [523] Patient 3 : Patient 3 is diagnosed with an inflammatory disorder including increased concentrations of CRP found in their plasma. Patient 3 begins to experience an impaired quality of life and begins to consume more processed foods. Patient 3 attends a follow-up visit with their healthcare professional. Patient 3 completes the SCID-5 and a form implementing use of the FCI to determine the presence of any psychological factors affecting the inflammatory disorder observed at baseline. Patient 3 obtains a high score on the FCI, which is correlated with having intense current food cravings. It is determined that the impaired quality of life experienced by Patient 3 delays recovery from the inflammatory disorder, as Patient 3 is reluctant to consume a healthy diet . Patient 3 is diagnosed with PFAOMC. Patient 3 is administered a RIMA, such as 300 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 3 is also administered an anti-inflammatory agent, such as 800 mg of ibuprofen three times a day for 16 weeks. At the same time, Patient 3 is also administered an anti-craving agent, such as 50 mg of naltrexone daily for 16 weeks. After the 16-week period, Patient 3 again completes a form implementing the FCI. Patient 3 is expected to exhibit fewer, less intense food cravings and show improvement in psychological factors affecting the inflammatory disorder in comparison with baseline levels. Patient 3 shows an improvement in PFAOMC. Patient 3 also exhibits lower levels of CRPs in their blood by eating fewer processed foods as prescribed by their healthcare professional. [524] Patient 4 : Patient 4 is diagnosed with a sleep disorder after undergoing a polysomnogram. Patient 4 begins to experience health anxiety. Patient 4 attends a follow-up visit with their healthcare professional. Patient 4 completes the SCID-5 and a form implementing use of the HAM-A to determine the presence of any psychological factors affecting the sleep disorder observed at baseline. Patient 4 is diagnosed with a 2023-12-14 generalized anxiety disorder using SCID and obtains a score of 27 on the HAM-A. Patient 4 is diagnosed with a generalized anxiety disorder, moderate anxiety, not PFAOMC. [525] Patient 5 : Patient 5 is diagnosed with a musculoskeletal condition of fibromyalgia after fulfilling the American College of Rheumatology diagnostic criteria for fibromyalgia. Patient 5 begins to experience thanatophobia. Patient 5 attends a follow-up visit with their healthcare professional. Patient 5 completes the SCID-5 and a form implementing use of the STAI to determine the presence of any psychological factors affecting the musculoskeletal condition observed at baseline. Patient 5 obtains a score of 60 on the STAI, which is correlated with heightened anxiety. It is determined that the thanatophobia experienced by Patient 5 exacerbates the course of the musculoskeletal condition, as Patient 5 is unable to adhere to their prescribed medication regimen. Patient 5 is diagnosed with PFAOMC. Patient 5 is administered 150 mg of a RIMA orally twice a day for a period of 16 weeks. At the same time, Patient 5 is also administered an anxiolytic agent, such as 10 mg of lorazepam once a day for 16 weeks. After the 16-week period, Patient 5 again completes a form implementing the STAI. Patient 5 is expected to exhibit fewer symptoms of thanatophobia and show improvement in psychological factors affecting the musculoskeletal condition in comparison with baseline levels. Patient 5 shows an improvement in PFAOMC. [526] Patient 6 : Patient 6 is diagnosed with a renal failure based on the results of blood and urine tests. Patient 6 begins to experience disease phobia with consequent alcohol consumption. Patient 6 attends a follow-up visit with their healthcare professional. Patient 6 completes the SCID-5 and a form implementing use of the Addiction Severity Index to determine the presence of any psychological factors affecting the renal disorder observed at baseline. Patient 6 obtains 0.12 composite score on the Alcohol Problem Area, which is correlated with a mild problem severity without a diagnosis of Alcohol Use Disorder by the SCID-5. It is determined that alcohol consumption experienced by Patient 6 exacerbates the course of the renal disorder, as Patient 6 is unable to adhere to instructions provided by their healthcare professional. Patient 6 is diagnosed with PFAOMC. Patient 6 is administered a RIMA, such as 150 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 6 is also administered an NMDA receptor agent, such as acamprosate, for 16 weeks. After the 16-week period, Patient 6 again completes a form implementing the Addiction Severity Index. Patient 6 is expected to exhibit fewer symptoms of alcohol consumption and show improvement in psychological factors affecting the renal disorder in comparison with baseline levels. Patient 6 shows an improvement in PFAOMC and renal function. [527] Patient 7 : Patient 7 is diagnosed with a hematological disorder following administration of a blood test. Patient 7 begins to experience persistent somatization. Patient 7 attends a follow-up visit with their healthcare professional. Patient 7 completes the SCID-5 and a form implementing use of the Somatic Symptom Scale and the DSI to determine the presence of any psychological factors affecting the renal disorder observed at baseline. Results of the DSI reflect the existence of several stressors in Patient 7’s daily life, but no Somatic Symptom Disorder by SCID-5. Patient 7 is diagnosed with PFAOMC. It is determined that 2023-12-14 the persistent stressors experienced by Patient 7 prolong the treatment of the hematological disorder. Patient 7 is diagnosed with PFAOMC. Patient 7 is administered a RIMA, such as 300 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 7 is also administered a beta blocker, such as 20 mg of propranolol twice a day for 16 weeks. After the 16-week period, Patient 7 again completes a form implementing the DSI. Patient 7 is expected to exhibit fewer symptoms of persistent stress and show improvement in psychological factors affecting the hematological disorder in comparison with baseline levels. Patient 7 shows an improvement in PFAOMC and hematologic indices. [528] Patient 8 : Patient 8 is diagnosed with a neurodegenerative disorder following a clinical examination by a neurologist. Patient 8 begins to experience an anniversary reaction. Patient 8 attends a follow-up visit with their healthcare professional. Patient 8 completes SCID-5, Clinician Administered PTSD Scale (CAPS) and a form implementing use of the Civilian M-PTSD Scale to determine the presence of any psychological factors affecting the neurodegenerative disorder observed at baseline. Results of SCID and CAPS reflect the existence of PTSD in Patient 8, which is another mental health disorder, not PFAOMC. [529] Patient 9 : Patient 9 is diagnosed with cancer. Patient 9 begins to experience conversion symptoms. Patient 9 attends a follow-up visit with their healthcare professional. Patient 9 completes the SCID-5 and a form implementing use of the HAM-A to determine the presence of any psychological factors affecting the cancer observed at baseline. Patient 9 obtains a score of 15 on the HAM-A, which is correlated with symptoms of mild anxiety. However, a diagnosis of an anxiety-related disorder is not warranted based on the SCID. Patient 9 is diagnosed with PFAOMC. It is determined that the conversion symptoms experienced by Patient 9 interferes with treatment of cancer. Patient 9 is diagnosed with PFAOMC. Patient 9 is administered a RIMA, such as 150 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 9 is also administered a psychedelic, e.g., 25 mg psilocybin, twice during drug-assisted psychological support sessions during the 16-week period, such as according to published methods. After the 16-week period, Patient 9 again completes a form implementing the HAM-A. Patient 9 is expected to exhibit fewer conversion symptoms and show improvement in psychological factors affecting the cancer in comparison with baseline levels. Patient 9 shows an improvement in PFAOMC and in the clinical course of cancer. The psilocybin may improve the psychological factors e.g., by reducing symptoms of anxiety or depression or feelings of existential distress associated with the cancer diagnosis. [530] Patient 10 : Patient 10 is diagnosed with multiple sclerosis after undergoing a clinical examination and MRI. Patient 10 begins to experience symptoms of demoralization. Patient 10 completes the SCID-5 and a form implementing use of the HAM-D to determine the presence of any psychological factors affecting the neurological condition observed at baseline. Patient 10 obtains a score of 10 on the HAM-D, which is correlated with symptoms of mild depression. However, a diagnosis of a depressive disorder is not warranted unless a subject experiences a threshold number of depressive symptoms in a given period of time. Patient 10 is diagnosed with PFAOMC. It is determined that the demoralization symptoms experienced by Patient 10 2023-12-14 interferes with treatment of the neurological condition. Patient 10 is diagnosed with PFAOMC. Patient 10 is administered a RIMA, such as 300 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 10 is also administered an antidepressant, such as 200 mg of modafinil once a day for 16 weeks. After the 16-week period, Patient 10 again completes a form implementing the HAM-D. Patient 10 is expected to exhibit fewer demoralization symptoms and show improvement in psychological factors affecting the multiple sclerosis in comparison with baseline levels. Patient 10 shows an improvement in PFAOMC. Patient 10 also exhibits improvement in intensity, duration, and frequency of symptoms of multiple sclerosis. [531] Patient 11 : Patient 11 is diagnosed with a genetic disorder after undergoing genetic testing. Patient 11 begins to experience type A behavior. Patient 11 attends a follow-up visit with their healthcare professional. Patient 11 completes the SCID-5 and a form implementing use of the 24-item Multidimensional Type A Behaviour Scale to determine the presence of any psychological factors affecting the neurological condition observed at baseline. Patient 11 obtains results based on the SCID-5 that reflect the existence of obsessive-compulsive disorder, which is a mental health disorder, not PFAOMC. [532] Patient 12 : Patient 12 is diagnosed with a pulmonary condition after undergoing a chest x-ray. Patient 12 begins to experience maladaptive health behaviors. Patient 12 attends a follow-up visit with their healthcare professional. Patient 12 completes the SCID-5 and a form implementing use of the TAPQ to determine the presence of any psychological factors affecting the pulmonary condition observed at baseline. Patient 12 obtains results that reflect impaired perception of benefit in adhering to their prescribed medication regimen, and it is determined that the maladaptive health behaviors experienced by Patient 12 interferes with treatment of the pulmonary condition. Patient 12 is diagnosed with PFAOMC. Patient 12 is administered a RIMA, such as 150 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 12 is also administered an anti-inflammatory agent, such as 100 mg of lumiracoxib once a day for 16 weeks. After the 16-week period, Patient 12 again completes a form implementing the TAPQ . Patient 12 is expected to exhibit fewer maladaptive health behaviors and show improvement in psychological factors affecting the pulmonary condition in comparison with baseline levels. Patient 12 shows an improvement in PFAOMC. Patient 12 also exhibits improvement in intensity, duration, and frequency of symptoms of the pulmonary condition. [533] Patient 13 : Patient 13 is diagnosed with a urinary disorder after undergoing a urine test. Patient 13 begins to experience an irritable mood. Patient 13 attends a follow-up visit with their healthcare professional. Patient 13 completes the SCID-5 and a form implementing use of the POMS questionnaire to determine the presence of any psychological factors affecting the urinary disorder observed at baseline. Patient 13 obtains a high score in connection with the “tension-anxiety” mood state based on the questionnaire. It is determined that the increased irritability experienced by Patient 13 exacerbates the course of the urinary disorder due to poor sleep. Patient 13 is diagnosed with PFAOMC. Patient 13 is administered a RIMA, such as 300 mg of moclobemide orally twice a day for a period of 16 weeks. Following the 16-week period, Patient 13 again 2023-12-14 completes a form implementing the POMS questionnaire. Patient 13 is expected to exhibit more positive emotions and show improvement in psychological factors affecting the urinary disorder in comparison with baseline levels. Patient 13 shows an improvement in PFAOMC and in urinary disorder. [534] Patient 14 : Patient 14 is diagnosed with a hepatic disorder after undergoing a blood test. Patient 14 begins to experience symptoms of emotional numbing. Patient 14 attends a follow-up visit with their healthcare professional. Patient 14 completes the SCID-5 and a form implementing use of the CAPS to determine the presence of any psychological factors affecting the hepatic disorder observed at baseline. Patient 14 obtains a low CAPS score, and it is determined that Patient 14 does not have PTSD. However, the symptoms of emotional numbing experienced by Patient 14 exacerbate the course of the hepatic disorder. Patient 14 is diagnosed with PFAOMC. Patient 14 is administered a RIMA, such as 150 mg of moclobemide orally twice a day for a period of 16 weeks. At the same time, Patient 14 is also administered an antidepressant such as 37.5 mg solriamfetol a day for 16 weeks. Following the 16-week period, Patient 14 again completes a form implementing the CAPS . Patient 14 is expected to exhibit fewer symptoms of emotional numbing and show improvement in psychological factors affecting the hepatic disorder in comparison with baseline levels. Patient 14 shows an improvement in PFAOMC and liver function tests. [535] Additional exemplary treatment methods include any of the foregoing embodiments, but where any other disclosed RIMA is administered in place of moclobemide. Additional exemplary treatment methods include any of the foregoing embodiments, but where any other disclosed anti-hyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antidepressant, anti-hypertensive agent, or additional active agent is administered in place of the anti-hyperglycemic agent, antioxidant, anti-inflammatory agent, anxiolytic agent, antidepressant, anti-hypertensive agent, or additional active agent used with the patients. EXAMPLE 5: Study of Subjects with PFAOMC Based on Lifestyle-Related Risk Factors [536] A study is being conducted in subjects with PFAOMC to determine the efficacy of participating in a lifestyle modification program for treatment of PFAOMC such as IRARD or the other conditions, such as addiction, for example. [537] A campus is set up for subjects participating in the program, who are encouraged to stay on campus for up to 21 days, including overnight stays. Subjects undergo a full laboratory workup at the inception of the program. The campus includes a fitness room and juice bar, and subjects are given a diet of sprout-derived vegan, raw, organic food. Subjects are encouraged to participate in daily physical activities and attend didactic activities, such as lectures and workshops each day. Subjects are prohibited from consuming tobacco, alcohol, or other drugs during the program. [538] Respective contributions of various tracks e.g., immune (complementary medicine treatments targeting the immune system), regeneration (complementary medicine energy treatments), mindfulness (mindfulness, stress reduction and psychotherapy), and fitness (personal training sessions and targeted psychotherapy) are to be examined during the program. 2023-12-14 [539] Several baseline variables could potentially confound the interpretation of the statistical analyses’ results. These variables may include the following: (a) age; (b) gender; (c) marital status; (d) use of tobacco; (e) use of alcohol; (f) use of other addictive substances; (g) stress levels; (h) medical ailments; (j) use of psychotropic medications; and (i) use of other medications. The associations between the above variables and metabolic parameters are to be examined. [540] For the significance of these screening tests, a conservative cut-off of p < 0.20 will be employed. Any variable for which p > 0.20 will be ruled out as potentially confounding for that analysis. In the event that any factor fails to pass this screening test, it will be determined whether the requirements for analysis of covariance (ANCOVA) are met. If so, the potentially confounding factor will be controlled for in this manner. In the case of potentially confounding factors that do not meet the requirements for ANCOVA, stratified analyses will be performed in subgroups with and without the factor. If the above analyses do not eliminate any factor as playing a potentially confounding role, due caution will be exerted in the interpretation of the findings. [541] Data will be analyzed using the statistical package Statistica (StatSoft, Inc, Tulsa, OK). Time related differences will be assessed by one-way repeated-measures analysis of variance with the status of the program (pre- and post-) as the within subjects factor. General regression model analysis will be performed using a model in which the independent variable is the duration of the program with the metabolic indices as dependent variables. Both post-hoc and exploratory correlative analyses will be conducted using Pearson product-moment correlation. All analyses will be two-tailed with α < 0.05 is set as the threshold for statistical significance. Following the program, subjects are expected to exhibit improvements in symptoms of the other medical condition in PFAOMC (e.g., insulin resistance or obesity), such as decreased BMI, improved glucose tolerance, improved plasma concentrations of lipids, and a more stable metabolic profile. Subjects are also expected to exhibit improvements in PFAOMC, such as increased feelings of happiness and motivation. Longitudinal effects in subjects following the 21-day period is examined in subjects who choose to repeat the program. This study will focus on clinical records only; subjects participating in the program will not interact. [542] The foregoing description, for purposes of explanation, uses specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one of skill that specific details are not required to practice the invention. The foregoing description of specific embodiments is presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise methods, compositions, formulations, or the like disclosed; many modifications and variations are possible in view of the teachings. Embodiments were chosen and described to best explain the principles of the invention and its practical applications, through the elucidation of specific examples, and to thereby enable others in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated, when such uses are beyond the specific examples disclosed. Accordingly, the scope of the invention shall be defined solely by the following claims and their equivalents.

Claims

2023-12-14 CLAIMS The invention claimed is: 1. A method of treating a psychological factor affecting other medical conditions (PFAOMC) in a subject in need thereof, comprising administering to the subject a therapeutic combination comprising a first agent and a second agent, including pharmaceutically acceptable salts thereof, wherein: a. the first agent is a reversible monoamine oxidase inhibitor (RIMA); and b. the second agent is any of an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, and an antihypertensive agent. 2. The method of claim 1, wherein the RIMA is any of moclobemide, brofaromine, caroxazone, eprobemide, metralindole, minaprine, and pirlindole. 3. The method of claim 2, wherein the RIMA is moclobemide. 4. The method of claim 1, wherein the second agent is an antihyperglycemic agent. 5. The method of claim 4, wherein the antihyperglycemic agent is any of an insulin, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an ɑ-glucosidase inhibitor, a DPP-4 inhibitor, a SGLT2 inhibitor, and a dopamine receptor agonist. 6. The method of claim 4, wherein the antihyperglycemic agent is any of insulin glulisine, insulin aspart, insulin lispro, regular insulin, NPH insulin, glipizide, glyburide, gliclazide, glimepiride, repaglinide, nateglinide, metformin, rosiglitazone, pioglitazone, acarbose, miglitol, voglibose, sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin, dapagliflozin, canagliflozin, and bromocriptine. 7. The method of claim 6, wherein the antihyperglycemic agent is metformin. 8. The method of claim 1, wherein the second agent is an antioxidant. 9. The method of claim 8, wherein the antioxidant is any of ascorbic acid, glutathione, a flavonoid, alpha lipoic acid, beta-carotene, alpha-tocopherol, ubiquinone, lycopene, coenzyme Q10, ellagic acid, retinol, masoprocol, pramipexole, nitric oxide, allopurinol, pentoxifylline, melatonin, probucol, quercetin, acetylcysteine, N-acetylcysteine, acetyl-L-carnitine, and L-methylfolate. 10. The method of claim 9, wherein the antioxidant is N-acetylcysteine. 11. The method of claim 1, wherein the second agent is an anti-inflammatory agent. 12. The method of claim 11, wherein the anti-inflammatory agent is any of apremilast, prednisone, hydrocortisone, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, 2023-12-14 meclofenamate, mefenamic acid, nabumetone, naproxen, tolmetin, piroxicam, celecoxib, etoricoxib, aspirin, naproxen, meloxicam, apremilast, an anti-cytokine agent, and a selective COX-2 inhibitor. 13. The method of claim 12, wherein the anti-cytokine agent is any of adalimumab, etanercept, infliximab, and tocilizumab. 14. The method of claim 12, wherein the selective COX-2 inhibitor is lumiracoxib. 15. The method of claim 12, wherein the anti-inflammatory agent is ibuprofen. 16. The method of claim 1, wherein the second agent is an anxiolytic agent. 17. The method of claim 16, wherein the anxiolytic agent is any of a benzodiazepine, an azapirone, an alpha blocker, a beta blocker, an antidepressant, a barbiturate, a nonbenzodiazepine sedative, a hypnotic, nefazodone, pregabalin, mirtazapine, and gabapentin. 18. The method of claim 17, wherein the benzodiazepine is any of lorazepam, diazepam, alprazolam, clonazepam, chlordiazepoxide, and chlordiazepoxide/clidinium bromide. 19. The method of claim 18, wherein the benzodiazepine is lorazepam. 20. The method of claim 17, wherein the azapirone is buspirone. 21. The method of claim 17, wherein the barbiturate is any of pentobarbital, phenobarbital, and amobarbital. 22. The method of claim 17, wherein the hypnotic is any of zolpidem, zaleplon, and zopiclone. 23. The method of claim 1, wherein the second agent is an antidepressant. 24. The method of claim 23, wherein the antidepressant is any of a selective serotonin reuptake inhibitor (SSRI), a selective norepinephrine reuptake inhibitor (NRI), a serotonin and norepinephrine reuptake inhibitor (SNRI), a dual norepinephrine/dopamine reuptake inhibitor (NDRI), a tricyclic antidepressant (TCA), a noradrenaline and specific serotonergic antidepressant (NaSSA), a serotonin antagonist and reuptake inhibitor (SARI), and a norepinephrine-dopamine disinhibitor (NDDI). 25. The method of claim 24, wherein the SSRI is any of fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, vortioxetine, and vilazodone. 26. The method of claim 24, wherein the NRI is either of atomoxetine and reboxetine. 27. The method of claim 24, wherein the SNRI is any of desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine. 2023-12-14 28. The method of claim 24, wherein the NDRI is any of amineptine, bupropion, desoxypipradrol, dexmethylphenidate, difemetorex, diphenylprolinol, ethylphenidate, fencamfamine, fencamine, lefetamine, methylenedioxypyrovalerone, methylphenidate, nomifensine, O-2172, phenylpiracetam, pipradrol, prolintane, pyrovalerone, solriamfetol, tametraline, and WY-46824. 29. The method of claim 28, wherein the NDRI is bupropion. 30. The method of claim 24, wherein the TCA is any of amitriptyline, doxepin, clomipramine, nortriptyline, imipramine, desipramine, protriptyline, dosulepin, maprotiline, trimipramine, and amoxapine. 31. The method of claim 24, wherein the NaSSA is any of aptazapine, esmirtazapine, mianserin, mirtazapine, and setiptiline. 32. The method of claim 24, wherein the SARI is any of etoperidone, lorpiprazole, mepiprazole, nefazodone, and trazodone. 33. The method of claim 24, wherein the NDDI is any of agomelatine, fluoxetine, flibanserin, and mirtazapine. 34. The method of claim 23, wherein the antidepressant is any of amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine, phenelzine, tranylcypromine, isocarboxazid, selegiline, mirtazapine, nefazodone, trazodone, bupropion, a neurotropic agent, an adaptogen, an actoprotector, a nootropic, a eugeroic, a racetam, an antihypoxant, a cognitive enhancer, potassium orotate, asparkam, a psychedelic, solriamfetol, vilazodone, atomoxetine, milnacipran, dosulepin, duloxetine, escitalopram, venlafaxine, citalopram, fluoxetine, fluvoxamine, vortioxetine, reboxetine, sertraline, paroxetine, esketamine, ketamine, dextromethorphan/bupropion, naltrexone/bupropion, and lithium. 35. The method of claim 34, wherein the psychedelic is any of 3,4-methylenedioxymethamphetamine (MDMA), paramethoxyamphetamine, a 2C-x compound, 4-bromo-2,5-dimethoxyphenethylamine (2C-B), a 3C-x compound, a DOx compound, 2,5-dimethoxy-4-methylamphetamine (DOI), 3,4,5-trimethoxyamphetamine (TMA), a tryptamine, a benzofuran, an iboga alkaloid, an ergoline, a lysergamide, a phenethylamine, a benzocyclobutene derivative, a NBOMe derivative, a NBOH derivative, a NBMD derivative, a NBF derivative, a phenylcyclopropylamine derivative, DMMDA, DMMDA-2, a benzoxazine, an empathogen, an entactogen, a cannabinoid, a harmala alkaloid, a beta-carboline, ayahuasca, salvinorin A, salvinorin B, a piperazine, myristicin, elemicin, cryogenine, an active constituent of a species of Heimia , atropine, scopolamine, hyoscyamine, psilocybin, psilocin, DMT, 5-MeO-DMT, LSD, ketamine, esketamine, an active constituent of a species of Solanaceae , and an active constituent of Amanita muscaria mushrooms. 2023-12-14 36. The method of claim 34, wherein the antidepressant is solriamfetol. 37. The method of claim 34, wherein the antidepressant is a cognitive enhancer. 38. The method of claim 37, wherein the cognitive enhancer is any of D-serine, L-serine, L-theanine, caffeine, creatine, bacopa monnieri, rhodiola rosea, panax ginseng, ginkgo biloba, tanakan, salvia officinalis, lavandulaefolia, centella asiatica, nicotine, noopept, piracetam, phenotropil, a cholinergic, an amphetamine, citicoline, choline bitartrate, alpha-GPC, ethomersol, bemithyl, pyrazidol, actovegin forte, glutamine, bemethyl, mildronate, phenibut, armodafinil, modafinil, and phenylpiracetam. 39. The method of claim 38, wherein the cognitive enhancer is modafinil. 40. The method of claim 1, wherein the second agent is an antihypertensive agent. 41. The method of claim 40, wherein the antihypertensive agent is any of nimodipine, a diuretic, a beta blocker, an ACE inhibitor, an angiotensin II receptor blocker, a calcium channel blocker, an alpha blocker, an alpha-2 receptor agonists, a combined alpha and beta blocker, a central agonist, a peripheral adrenergic inhibitor, and a vasodilator. 42. The method of claim 41, wherein the antihypertensive agent is nimodipine. 43. The method of claim 41, wherein the antihypertensive agent is a beta blocker. 44. The method of claim 43, wherein the beta blocker is propranolol. 45. The method of claim 3, wherein the therapeutic combination comprises any of: a. moclobemide and metformin; b. moclobemide and nimodipine; c. moclobemide and propranolol; d. moclobemide and solriamfetol; e. moclobemide and modafinil; f. moclobemide and lumiracoxib; and g. moclobemide and ibuprofen. 46. The method of claim 3, wherein moclobemide is administered daily. 47. The method of claim 46, wherein the daily dose of moclobemide is between 50 mg and 600 mg. 48. The method of claim 47, wherein the daily dose of moclobemide is between 50 mg and 150 mg. 49. The method of claim 47, wherein the daily dose of moclobemide is between 150 mg and 600 mg. 2023-12-14 50. The method of claim 49, wherein the daily dose of moclobemide is between 300 mg and 600 mg. 51. The method of claim 46, wherein moclobemide is administered daily for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 10 weeks, at least 15 weeks, at least 16 weeks, or at least 20 weeks. 52. The method of claim 1, wherein the psychological factor is any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. 53. The method of claim 52, wherein the maladaptive health behavior is any of denial of symptoms, poor adherence to medical recommendations, and medication nonadherence. 54. The method of claim 1, further comprising treating the other medical condition in the subject. 55. The method of claim 54, wherein the other medical condition is any of an insulin resistance and related disorder (IRARD), hypertension, an inflammatory disorder, a sleep disorder, a musculoskeletal condition, a renal disorder, a hematological disorder, a neurodegenerative disorder, cancer, an allergy, an immunological condition, a neurological condition, an infection, a genetic disorder, an otolaryngological disorder, a pulmonary condition, a urinary or bladder disorder, a digestive disorder, a hepatic disorder, an ophthalmic condition, a dental or oral health issue, a vascular disorder, a gyneco- logical condition, a skin disorder, a rare disease, an endocrinopathy, and congestive heart failure . 56. The method of claim 55, wherein the other medical condition is any of an IRARD, hypertension, and an inflammatory disorder. 57. The method of claim 56, wherein the other medical condition is an IRARD. 58. The method of claim 57, wherein the IRARD is any of insulin resistance, glucoregulatory disorders, glucoregulatory disorders induced by treatment with mood stabilizers, glucoregulatory disorders induced by treatment with antipsychotics, glucoregulatory disorders induced by treatment with opioids, insulin resistance induced by pharmacotherapy, coronary artery disease, ischemic heart disease, obesity, stroke, being overweight, a genetic disorder, and polycystic ovary disease. 59. The method of claim 58, wherein the glucoregulatory disorder is any of prediabetes, diabetes, metabolic syndrome, obesity, and dyslipidemia. 60. The method of claim 56, wherein the other medical condition is hypertension. 61. The method of claim 60, wherein the hypertension is any of primary hypertension, secondary hypertension, resistant hypertension, malignant hypertension, white coat hypertension, hypertensive 2023-12-14 urgency, and isolated systolic hypertension. 62. The method of claim 61, wherein the malignant hypertension is a hypertensive emergency. 63. The method of claim 56, wherein the other medical condition is an inflammatory disorder. 64. The method of claim 63, wherein the inflammatory disorder is any of acne vulgaris, acid reflux or heartburn, age-related macular degeneration (AMD), an allergy, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, appendicitis, arteritis, arthritis, skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation, intestinal inflammation, neuroinflammation, ocular inflammation, brain inflammation, long COVID, a food allergy, post-treatment lyme disease syndrome, an ulcer, asthma, atherosclerosis, autoimmune disorder, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, burns, bursitis, cancer, cardiovascular disease, celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, congestive heart failure, conjunctivitis, colitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, lacrimal inflammation, and dementia. 65. The method of claim 55, wherein the genetic disorder is either of Prader-Willi syndrome (PWS) and a Prader-Willi-Like syndrome. 66. The method of claim 55, wherein the sleep disorder is any of insomnia, dyssomnia, and parasomnia. 67. The method of claim 55, wherein the musculoskeletal condition is any of arthritis, osteoporosis, and dystonia. 68. The method of either of claims 64 and 67, wherein the arthritis is any of osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathy, reactive arthritis, psoriatic arthritis, enteroarthritis associated with inflammatory bowel disease, Whipple and Behcet's disease, septic arthritis, gout, pseudogout, and Still's disease. 69. The method of claim 68, wherein the spondyloarthropathy is ankylosing spondylitis. 70. The method of claim 68, wherein the reactive arthritis is Reiter syndrome. 71. The method of claim 68, wherein the gout is any of gouty arthritis, crystalline synovitis, and metabolic arthritis. 72. The method of claim 68, wherein the pseudogout is calcium pyrophosphate deposition disease. 2023-12-14 73. The method of claim 55, wherein the renal disorder is renal failure. 74. The method of claim 55, wherein the hematological disorder is any of anemia, a clotting disorder, and polycythemia vera. 75. The method of claim 55, wherein the neurodegenerative disorder is either of Alzheimer's disease and Parkinson's disease. 76. The method of claim 55, wherein the neurological condition is any of seizure disorder, head trauma, multiple sclerosis, and tremor. 77. The method of claim 55, wherein the infection is either of a helicobacter pylori infection and a pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection. 78. The method of claim 55, wherein the pulmonary condition is either of chronic obstructive pulmonary disease (COPD) and interstitial lung disease. 79. The method of claim 55, wherein the urinary or bladder disorder is any of urinary incontinence, interstitial cystitis, and benign prostatic hyperplasia. 80. The method of claim 55, wherein the digestive disorder is any of gastroesophageal reflux, chronic gastritis, and a peptic ulcer. 81. The method of claim 55, wherein the hepatic disorder is any of cirrhosis, cholelithiasis, and hepatitis. 82. The method of claim 55, wherein the otolaryngological disorder is either of chronic otitis media and Meniere's disease. 83. The method of claim 55, wherein the ophthalmic condition is either of glaucoma and dry eye syndrome. 84. The method of claim 55, wherein the dental or oral health issue is a temporomandibular joint disorder. 85. The method of claim 55, wherein the vascular disorder is either of peripheral artery disease and venous insufficiency. 86. The method of claim 55, wherein the gynecological condition is endometriosis. 87. The method of claim 55, wherein the endocrinopathy is Cushing’s disease. 88. The method of claim 55, wherein the cancer is an NF-κB-induced inflammatory cancer. 89. The method of claim 64, wherein the cardiovascular disease is any of endocarditis, myocarditis, heart 2023-12-14 valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart abnormalities, vascular inflammation, arterial occlusive disease, inflammatory cardiac hypertrophy, peripheral arterial disease, aneurysm, embolism, incision, pseudoaneurysm, vascular malformation, vascular nevus, thrombosis, varicose veins, stroke, cardiac arrest, and carditis. 90. The method of claim 89, wherein the vascular inflammation is arteritis, phlebitis, or vasculitis. 91. The method of claim 89, wherein the arterial occlusive disease is arteriosclerosis or stenosis. 92. The method of claim 1, wherein the subject has a co-occurring mental health disorder. 93. The method of claim 1, wherein the co-occurring mental health disorder is any of a depressive disorder, a mood disorder, an anxiety disorder, a trauma- or stressor-related disorder, obsessive-compulsive disorder (OCD), a neurocognitive disorder, a feeding or eating disorder, intermittent explosive disorder, an addiction disorder, a substance use disorder, an impulse control disorder, compulsive buying disorder, repetitive self-mutilation syndrome, a nonparaphilic sexual addiction or paraphilia, a personality disorder, and attention deficit hyperactivity disorder (ADHD). 94. The method of claim 1, wherein treating the psychological factor affecting other medical conditions in the subject results in an improvement in the psychological factor. 95. The method of claim 94, wherein the improvement in the psychological factor is an improvement in any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. 96. The method of claim 94, wherein the improvement in the psychological factor is determined using an outcome measure . 97. The method of claim 96, wherein the outcome measure is any of a physiological measure, a patient-centered outcome measure, a behavioral factor measure, or a psychodiagnostic or psychometric tool . 98. The method of claim 97, wherein the psychodiagnostic or psychometric tool is any of the Structured Clinical Interview for DSM-5, the Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Daily Stress Inventory, the Perceived Stress Scale, the Profile of Mood States questionnaire, the Yale Food Addiction Scale, the Eating Disorder Examination Questionnaire, the Food Craving Inventory, the Yale-Brown Obsessive-Compulsive Scale, the Food Craving Questionnaires, the Three-Factor Eating Questionnaire, the Relationship Patterns Questionnaire, the Treatment Adherence Perception Questionnaire, the Reward Deficiency Syndrome Questionnaire, the Genetic Addiction Risk Severity 2023-12-14 (GARS) test, the Clinician-Administered PTSD Scale, and the Civilian Mississippi Post-Traumatic Stress Disorder (PTSD) Scale. 99. The method of claim 1, wherein treating the psychological factor affecting other medical conditions in the subject results in an improvement in the other medical condition. 100. The method of claim 99, wherein the improvement in the other medical condition is an improvement in any of an insulin resistance and related disorder (IRARD), hypertension, an inflammatory disorder, a sleep disorder, a musculoskeletal condition, a renal disorder, a hematological disorder, a neurodegenerative disorder, cancer, an allergy, an immunological condition, a neurological condition, an infection, a genetic disorder, an otolaryngological disorder, a pulmonary condition, a urinary or bladder disorder, a digestive disorder, a hepatic disorder, an ophthalmic condition, a dental or oral health issue, a vascular disorder, a gyneco- logical condition, a skin disorder, a rare disease, an endocrinopathy, and congestive heart failure . 101. The method of claim 100, wherein the improvement in the other medical condition is an improvement in any of an IRARD, hypertension, and an inflammatory disorder. 102. The method of claim 99, wherein the improvement in the other medical condition is determined using an outcome measure . 103. The method of claim 102, wherein the outcome measure is any of a physiological measure, a patient-centered outcome measure, or a behavioral factor measure. 104. A pharmaceutical kit for treating a psychological factor affecting other medical conditions (PFAOMC) in a subject, comprising a first pharmaceutical composition and a second pharmaceutical composition, wherein: a. the first pharmaceutical composition comprises a RIMA, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient; and b. the second pharmaceutical composition comprises a second agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient; and wherein the second agent is any of an antihyperglycemic agent, an antioxidant, an anti-inflammatory agent, an anxiolytic agent, an antidepressant, and an antihypertensive agent. 105. The pharmaceutical kit of claim 104, wherein the second agent is any of metformin, nimodipine, propranolol, solriamfetol, modafinil, lumiracoxib, ibuprofen, a PDE-1 inhibitor, a PDE-2 inhibitor, a PDE-3 inhibitor, a PDE-4 inhibitor, a PDE-5 inhibitor, N-acetylcysteine, meldonium, acetyl-L-cysteine, phenylpiracetam, vitamin D, L-methylfolate, buspirone, an anticonvulsant, lorazepam, a benzodiazepine, lithium, a triptan, acamprosate, naltrexone, vivitrol, buprenorphine, and a barbiturate. 2023-12-14 106. The pharmaceutical kit of claim 104, wherein the first agent and the second agent are any of: a. moclobemide and metformin; b. moclobemide and nimodipine; c. moclobemide and propranolol; d. moclobemide and solriamfetol; e. moclobemide and modafinil; f. moclobemide and lumiracoxib; and g. moclobemide and ibuprofen. 107. The pharmaceutical kit of claim 104, wherein the RIMA is formulated for any of intravenous, intramuscular, subcutaneous, and oral administration. 108. The pharmaceutical kit of claim 104, wherein the second agent is formulated for any of intravenous, intramuscular, subcutaneous, and oral administration. 109. The pharmaceutical kit of claim 104, wherein the RIMA is in unit dosage form. 110. The pharmaceutical kit of claim 109, wherein the unit dosage form is any of an immediate release, a controlled release, a sustained release, an extended release, and a modified release formulation. 111. The pharmaceutical kit of claim 104, wherein the second agent is in unit dosage form. 112. The pharmaceutical kit of claim 111, wherein the unit dosage form is any of an immediate release, a controlled release, a sustained release, an extended release, and a modified release formulation. 113. The method of claim 1, further comprising administering an additional active agent. 114. The pharmaceutical kit of claim 104, further comprising an additional active agent. 115. The method of claim 113 or the pharmaceutical kit of claim 114 , wherein the additional active agent is any of an amino acid, an antioxidant, an anti-inflammatory agent, an analgesic, an antineuropathic or antinociceptive agent, an antimigraine agent, an anxiolytic, an antidepressant, an antipsychotic, an anti-PTSD agent, a cannabinoid, a dissociative, an immunostimulant, an anti-cancer agent, an anti- emetic, an orexigenic, an antiulcer agent, an anticholinergic agent, an anti-ischemic agent, an anti- histamine, an antihypertensive, an anticonvulsant, an antiepileptic, a bronchodilator, a mood stabilizer, a neuroprotectant, a serotonergic agent, a neuroactive agent, a psychedelic, an entactogen or empathogen, an entheogen, a MAOI, a tryptamine, a terpene, a phenethylamine, a sedative, a stimulant, an opioid modulator, an NMDA receptor agent, a vitamin, an SSRI, a NRI, an SNRI, a NDRI, a TCA, a NaSSA, a SARI, a NDDI, a benzodiazepine, or a phosphodiesterase inhibitor. 2023-12-14 116. Use of the therapeutic combination of any of the foregoing claims to treat PFAOMC in a subject. 117. A method of treating a psychological factor affecting other medical conditions (PFAOMC) in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a reversible monoamine oxidase inhibitor (RIMA), or a pharmaceutically acceptable salt thereof. 118. The method of claim 117, wherein the RIMA is any of moclobemide, brofaromine, caroxazone, eprobemide, metralindole, minaprine, and pirlindole. 119. The method of claim 118, wherein the RIMA is moclobemide. 120. The method of claim 119, wherein moclobemide is administered daily. 121. The method of claim 120, wherein the daily dose of moclobemide is between 50 mg and 600 mg. 122. The method of claim 121, wherein the daily dose of moclobemide is between 50 mg and 150 mg. 123. The method of claim 121, wherein the daily dose of moclobemide is between 150 mg and 600 mg. 124. The method of claim 123, wherein the daily dose of moclobemide is between 300 mg and 600 mg. 125. The method of claim 120, wherein moclobemide is administered daily for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 10 weeks, at least 15 weeks, at least 16 weeks, or at least 20 weeks. 126. The method of claim 117, wherein the psychological factor is any of psychological distress, a pattern of interpersonal interaction, a coping style, a maladaptive health behavior, anhedonia, emotional numbing, and affective flattening. 127. The method of claim 126, wherein the maladaptive health behavior is any of denial of symptoms, poor adherence to medical recommendations, and medication nonadherence. 128. The method of claim 117, further comprising treating the other medical condition in the subject. 129. The method of claim 128, wherein the other medical condition is any of an IRARD, hypertension, and an inflammatory disorder. 130. The method of claim 117, wherein treating the psychological factor results in an improvement in the psychological factor. 131. The method of claim 117, wherein treating the psychological factor results in an improvement in the other medical condition. 132. Use of the pharmaceutical composition of any of claims 117-131 to treat PFAOMC in a subject.