The prescriber’s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression

Abstract This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

MAOIs: Introduction
The classic monoamine oxidase inhibitors (MAOIs), which include phenelzine, tranylcypromine, and isocarboxazid, inhibit monoamine oxidases (MAOs; A and B) in a nonselective and irreversible manner, resulting in the reduced breakdown of the neurotransmitters serotonin, norepinephrine, and dopamine. 1 The absolute amount of neurotransmitters is therefore increased within as well as outside the neuron (in contrast to treatment with selective serotonin reuptake inhibitors [SSRIs], serotonin and norepinephrine reuptake inhibitors [SNRIs], or tricyclic antidepressants [TCAs], which yields only a relative, extracellular increase in the concentration of neurotransmitters within the synaptic cleft). This mechanism (affecting all 3 major neurotransmitters) 2 may explain, at least in part, the antidepressant effect of these medications (see also point 4.7.4).
1 Indications 1.1 Following insufficient response to a modern antidepressant (eg, an SSRI/SNRI, mirtazapine, bupropion) and/or a TCA, either as monotherapy treatment or with an augmentation agent (eg, lithium). MAOIs should always be considered in cases of treatment-resistant depression, including I those melancholic in nature (see point 2.4). 1.2 MAOIs are typically indicated prior to electroconvulsive therapy (ECT), 3 except when a rapid response to treatment is imperative (eg, imminent suicide risk, inanition, and catatonia).
Note: MAOIs can prove effective even after (failed) ECT treatment 4 or ketamine infusion.
1.3 MAOIs may also be effective for treatment-resistant anxiety and panic disorders. 5,6 1.4 MAOIs can also be considered in the treatment of other diagnoses based on individualized considerations and patient preferences.
2 Selection criteria 2.1 Both phenelzine and tranylcypromine are highly effective antidepressants, although individual responses can differ significantly. 7 Fewer comparative data are available for isocarboxazid; it is therefore considered as a third/final choice among MAOIs, and is further discussed in Appendix A. II 2.2 This guide does not discuss other (nonclassic) MAOIs, such as the selective MAO-A inhibitor moclobemide (rather ineffective in treatment-resistant depression) and the selective MAO-B inhibitor rasagiline (not indicated for use as an antidepressant). 8 Note: At high doses, the selective MAO-B inhibitor selegiline also exhibits activity as an MAO-A inhibitor, and appears to be an effective (nonselective MAOI) antidepressant. As a trade-off for its (presumably) reduced efficacy compared with the classic MAOIs, selegiline may present with a better tolerability profile, and may in the future have a significant role to play in the treatment of mood disorders in selected patient populations, both as an ("off-label") oral antidepressant 9 and in its approved form as a transdermal antidepressant 10 (available in 3 doses ranging from 6 to 12 mg/24 hour, which come with a variable, dose-dependent degree of dietary restrictions; at the lowest dose, there are none). 11 2.3 In the case of premorbid anxiety disorder, or in the case of comorbid panic disorder, phenelzine (GABA activity) may be indicated over tranylcypromine (see also the "note" under point 2.4). 2.4 If psychomotor retardation is a prominent symptom, or in the case of a predominantly endogenous (melancholic) depression, tranylcypromine 12 may be indicated over phenelzine.
Note: Several clinician members of the Workgroup wish to emphasize that the clear-cut categorization observed in much of the original literature-reserving phenelzine for states of anxious depression and tranylcypromine for the more lethargic, melancholic manifestations-does not correlate with the weight of decades-long clinical experience, and is therefore no longer strictly tenable. They refer to severe cases of anxious depression responding to treatment with tranylcypromine (complete and sustained remission; no exacerbation of anxiety symptoms). They note, in addition, that phenelzine treatment remains particularly indicated for patients whose anxiety predates their depression.

2.5
The side-effect profiles of phenelzine (a hydrazine derivative) and tranylcypromine (nonhydrazine) differ considerably. 13,14 The side effects of phenelzine may be experienced as more troublesome: 15  including clomipramine and imipramine) or an agent with significant activity as a serotonin releaser, then a washout period is required (duration is 5 times the half-life of the SRI or serotonin releaser) prior to MAOI treatment initiation.
Note: In practical terms, this means for most SSRIs and SNRIs that 8 days will suffice as a washout period, with vortioxetine and fluoxetine being notable exceptions: (a) Vortioxetine has a median elimination half-life of approximately 66 hours. 24 The calculation of the minimum washout duration comes out to 14 days. (b) Fluoxetine has an elimination half-life of 1 to 4 days, but that of its active metabolite, norfluoxetine, ranges from 7 to 15 days 25 ; therefore, the calculation of the minimum washout duration comes out to 10 weeks, 26 although a cautious start of MAOI after 6 weeks is deemed permissible in most guidelines. 27,28 Note: a longer washout (>6 weeks) is recommended if high doses of fluoxetine were used.
4.1. 5 The requirement (in the discussed cases) of a washout period prior to MAOI initiation may have important clinical implications. The patient is likely to be severely ill, so that even a short time with no antidepressant relief may prove intolerable. The addition of a different, "bridging" agent may be considered-nortriptyline (TCA), lithium, and low-dose (≤15 mg) mirtazapine are prime candidates for this role, as they can safely be added both to the serotonergic agent that is being (or has been) tapered off, and to the MAOI that will be started after the washout period. 4.1. 6 The prescribing physician alerts the patient's primary care doctor, and directs him/her to this Prescriber's guide.
Note: Before undergoing dental work, the patient needs to alert the dentist that he/she is taking a classic MAOI. When administering a local anesthetic, the dentist exercises the proper care concerning the choice of an appropriate anesthetic agent and dose (eg, avoids cocaine, considers using lower doses of adrenaline and reducing treatment duration, or uses felypressin instead of adrenaline in patients with cardiovascular or cerebrovascular conditions). If possible, additional measures may be employed to avoid intravascular injection of the local anesthetic (fractionated injection and aspiration test).
Note: In the case of phenelzine treatment, supplementation with pyridoxine hydrochloride (vitamin B6) is advisable; see also point 6.6.3(e). It may be added either at the start of phenelzine treatment, or if/when related side effects appear (clinician's choice). In the first instance, administration of a benzodiazepine (alprazolam or lorazepam) and/or propranolol is useful.
Note: This side effect may be observed incidentally in the context of self-recorded BP measurements by the patient, and should be reported to the physician. Given the limited duration of this BP increase, a cautious approach to treatment is in order (to avoid the risk of hypotensive overshoots). One may consider the following III Some clinicians prefer to treat orthostatic hypotension with dopamine antagonists, such as domperidone or metoclopramide (see Zandee et al. 2017), but risk-benefit balance must be considered (same with fludrocortisone).

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V. Van  may be observed within several days/weeks, the full antidepressant effect of a given dose may be achieved only after 4 to 6 weeks; with phenelzine, this may even take 8 to 12 weeks (due to an assumed initial inhibition of its own metabolism, as phenelzine is both a substrate and inhibitor of MAO). 33

Aside from the known inhibition of MAO, both
MAOIs likely have additional antidepressant mechanisms: with tranylcypromine, a working hypothesis (confirmatory research required) includes potential activity as a norepinephrine reuptake inhibitor at a dose of 40 to 60 mg, 34 and potential dopamine-releasing activity at 100 mg; 35 phenelzine is metabolized on a dose-related basis to several metabolites, including β-phenethylamine (releases dopamine and norepinephrine) and β-phenylethylidinehydrazine (increases brain GABA levels).
Note: In older literature, it was advised to lower the dose gradually following antidepressant response, because a low "maintenance dose" would suffice for maintaining the achieved MAO inhibition. Because of a high chance of depressive relapse, this method is no longer advised. It is best to continue treatment with the same dose with which antidepressant response was achieved (exception: significant/persistent agitation or overstimulation may resolve with dose reduction).
5 Tyramine-restricted diet 26 5.1 The patient must follow a tyramine-restricted diet, as the inhibition of MAO reduces the capacity for a breakdown of exogenous tyramine in the gastrointestinal tract and liver, leading to BP increases via peripheral norepinephrine release (which can, in serious cases, result in a hypertensive urgency or emergency). 36 Tyramine is formed by the decarboxylation of tyrosine, and may be present in high quantities in some foodstuffs which have been fermented, matured, or spoiled. Examples include: • some aged cheeses; • some artisan beers which use natural yeasts instead of starter cultures, such as the Belgian "Lambic" beer; • some fermented meats (eg, some salamis); • fermented products such as tempeh, miso, soy sauce, sauerkraut, marmite, and kimchi.
For extensive elaboration, see "The Prescriber's guide to the MAOI diet-thinking through tyramine troubles." 37 Additionally noteworthy: • Thanks to modern food standards, the amount of tyramine present in many (but not all) foodstuffs has been considerably reduced (compared to the 1950s and the 1960s, when MAOIs were first on the market). This means MAOI treatment is safer now than ever, given the limited risk of excessive tyramine ingestion. • Tyramine sensitivity differs significantly from person to person. In tyramine-sensitive MAOI patients, consumption of 10 mg of tyramine in a meal can cause a noticeable BP increase; in the "average" MAOI patient, this may require closer to 20+ mg of tyramine. • BP increase after excessive tyramine consumption is typically maximal within 2 hours. SRIs or agents with significant serotonin-releasing activity. The risk is serotonin toxicity.
Note: Serotonin toxicity 39 (or serotonin syndrome) is a dose-related response; symptoms (such as tremor, hyperreflexia, and clonus) are placed on a spectrum, 40 whereby the severity is determined by the elevation of intrasynaptic serotonin (which is mediated by serotonin reuptake inhibition and/or presynaptic release of serotonin).

Great caution is advised when combining MAOIs with:
Monoamine releasers without significant serotonergic activity (certain indirect sympathomimetics). The risk is a hypertensive urgency or emergency.
Note: Combining MAOIs with certain other (direct or indirect) sympathomimetics is comparatively safer, and is therefore possible if therapeutically indicated (caution warranted; use low testing dose, slow dose increases, while considering the risk-benefit balance). See also points 6.4 to 6.6.
6.2 Pharmacokinetic interactions 6.2.1 Tranylcypromine is an inhibitor of i.a. CYP2A6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and CYP2B6; clinically significant interactions are unlikely at typical therapeutic doses, with possible exceptions being the inhibition of CYP2A6 ("low clinical relevance" due to IV Note: For doses greater than those recommended in the product information, additional informed consent may be required in some jurisdictions. the "very minor role" CYP2A6 plays in the metabolism of drugs), 35  Note: Washout period required prior to starting MAOI (typical duration is 5 times the half-life of the SRI).

Combinations that must be avoided (because of serotonin-releasing activity): (a) Amphetamines in medium/high doses (b) Fenfluramine
Note: Washout period required prior to starting MAOI (typical duration is 5 times the half-life of the serotonin-releasing agent).

6.3.3
Combinations that must be avoided (because of various/other mechanisms of interaction; paucity of literature data): (a) Some antihypertensives (eg, methyldopa and reserpine).
(b) Pancuronium (a muscle relaxant that is sometimes used with general anesthetics). 49 (c) Various illicit drugs (eg, cocaine and MDMA) and some licit/illicit supplements (eg, ayahuasca and St. John's wort).
Note: With St. John's wort (Hypericum perforatum), the risk of serious interactions (eg, serotonin toxicity) is likely limited-but a lack of therapeutic rationale implies a negative risk-benefit balance.
(d) Concomitant use of other (classic or reversible/ selective) MAOIs (eg, isocarboxazid, pargyline, selegiline, rasagiline, isoniazid, iproniazid, and moclobemide); there is often a lack of rationale for concurrent use of multiple MAOIs (as well as a paucity of literature data on the relative safety of such combinations). This absolute contraindication includes all agents with potent, albeit perhaps incidental, MAOI activity, such as methylthioninium chloride (methylene blue) and linezolid.
Note: Washout period required when switching from MAOI to MAOI (most guidelines advise 14 days if the first agent was also an irreversible MAOI 27 -but expert clinicians have deviated from this precept in cases that allow for cautious/constant monitoring; see also point 7).
6.4 Relative contraindications (strong) 6.4.1 Combinations that are, in principle, advised against because of activity as monoamine releaser (without significant serotonergic activity):

(a) Amphetamines in low doses
Note: Lisdexamphetamine is potentially safer than other amphetamines (including methamphetamine and dexamphetamine), owing to its lower peak plasma concentrations and longer T max .

(b) Ephedrine and pseudoephedrine
Note: Caution is required concerning decongestants and cough medicines that contain these agents.
Note: Ephedrine is safer than amphetamine (lower potency), and pseudoephedrine is safer than ephedrine (same reason).  Note: Of the remaining TCAs, amitriptyline has the most pronounced serotonergic activity; the combination (amitriptyline + MAOI) does not, however, result in serotonin toxicity. Therefore, there is no risk of serotonin toxicity when combining nortriptyline, desipramine, and so on with MAOIs. Nevertheless, caution is advised when administering this combination (MAOI + TCA), based on the specific properties of the selected augmenting agent (eg, desipramine is known to increase endogenous norepinephrine concentrations and to potentiate its vasoconstrictor effects). In counterpoint, the combination (MAOI + TCA) may offer some protection against excessive tyramine consumption, as NRIs attenuate the tyramine pressor response. 13 Note: As TCAs are not a pharmacologically homogenous group, drug selection is of prime importance; 55 an exceedingly low starting dose and slow uptitration to a decreased maximum dose is required (suggested starting dose: ¼ of the typical starting dose). The order in which combination treatment is best administered (TCA first vs MAOI first vs simultaneous initiation and uptitration) remains a point of some contention. Much of the older literature that advocates against "MAOI first," is based on case reports that (a) stem from a time when knowledge of serious drug-drug interactions was less extensive (eg, imipramine-induced serotonin toxicity in MAOI patients), 56 and (b) feature high starting doses for the TCA and/or an entirely too rapid rate of subsequent dose increases. Following a comprehensive reevaluation of the relevant data, 57 it was concluded that the efficacy and safety of the TCA + MAOI combination is unlikely to be governed by the order of treatment initiation. The Workgroup wishes to emphasize the need for strict adherence to the fundamental tenets of good pharmacology, as discussed above.
Note: Ketamine 58 and esketamine 59 appear, in principle, likewise safe to combine (sparse literature data at present; low starting dose, cautious uptitration, and BP monitoring advised).
While the above augmenting agents may be safely co-administered with an MAOI, the Workgroup wishes to underline once more that cautious introduction of the augmenting agent is in order.

To manage side effects:
(a) For insomnia: trazodone VI ,40 (50 mg) or mirtazapine (7.5-15 mg) or doxepin (5-25 mg) Note: These agents have no significant SRI activity at the doses mentioned. 40 Note: Insomnia is a prominent side effect of MAOI treatment (and may be worse with tranylcypromine than with phenelzine). While the severity of this side effect may lessen during long-term treatment, it rarely dissipates fully. Patients may be advised to take the last dose earlier in the day VII ; this may help somewhat. If improvement is insufficient, consider adding zolpidem or lorazepam.
V In patients on MAOIs with orthostatic hypotension, exogenous epinephrine may result in a reversal of the typical BP effect of large doses of epinephrine, from a pressor response (mediated by alpha receptors) to a depressor response (mediated by beta-2 receptors). If administration of epinephrine causes increased hypotension, further epinephrine is contraindicated and alternative pressors will be required. VI We make mention of two recent case reports in the Dutch literature, 89 in which interactions (possible "serotonin syndrome") were reported following comedication with low-dose trazodone (50-100 mg) in tranylcypromine patients. A response was formulated by a pharmacist at the "Geneesmiddel Informatie Centrum' of the Royal Dutch Pharmacists' Association (KNMP): 'The case reports have insufficient information to ascertain whether these were cases of serotonin syndrome, and whether the symptoms occurred because of the tranylcypromine-and trazodone-comedication." Additionally, mechanistic substantiation of the interaction is hardly possible (see Reinders 2014 for "citation" and paraphrase).
VII Seemingly paradoxically, for some patients it helps to take the daily dose(s) closer to bedtime (reason unclear; drug idiosyncrasy is a proffered explanation). 7 Interim conclusions (a) The above recommendations are aimed at preventing/limiting the risk of serious drug-drug interactions; they are formulated, as befitting of a specialist-consensus standard, in a general and undifferentiated sense. Several clinician members of the Workgroup wish, therefore, to reiterate the purpose of this document: it is a guide, not a rulebook. The best medical care is delivered on a case-by-case basis, and expert clinicians have been known to deviate from the precepts discussed in this Interactions section (or in this guide in general). For example: • Successful initiation of MAOI treatment in patients on disulfiram (strong relative contraindication). This combination may induce confusional states "akin to delirium," 20 which may be explained mechanistically (unconfirmed) by comedication-induced increases in aldehyde concentrations. 61 Even so, expert clinicians report having used this combination without serious adverse events. • Successful comedication in MAOI partial responders with fulldose trazodone (200-400 mg), or mirtazapine (45-60 mg), or (in tranylcypromine cases) amitriptyline (80-150 mg). 62 • Successful, albeit cautious, coadministration of methadone without serious adverse events. • Successful, albeit cautious, comedication with either lisdexamphetamine or methamphetamine to remedy phenelzine-induced daytime somnolence that did not adequately respond to methylphenidate or modafinil. • Successful treatment with very high MAOI doses (that exceed the typically recommended maximum doses)-eg, 120 to 170 mg tranylcypromine 63 or 120 mg phenelzine. 64 • Successful cross-taper 65 (or even abrupt switch) 66 from MAOI to MAOI (note that additional research is required; this strategy remains highly controversial).
Note that these are treatment strategies used by experts; they are not to be used without great caution and consideration (and a second opinion).
In summary, this document is a detailed introduction to the use of classic MAOIs in clinical settings; it is meant merely to guide-not to restrain experienced practitioners, whose insights and intuitions may overrule these general considerations.
(b) In the past, combining MAOIs with other pharmaceuticals was considered "too risky"-often without a solid clinical or pharmacological basis. 67 Assuming proper adherence to the discussed considerations, there is no sound reason to categorically exclude potentially effective combination therapies. It is wise to abide by the age-old adage "start low, go slow." As a counterweight to the alleged risks of MAOI treatment-with or without the addition of an augmenting agent-one must consider the known risk of longstanding depression left improperly treated; the costs to the patient, to their loved ones, and to society are immense. It is vital, therefore, that treatment regimens are optimized 68  This BP increase is self-limiting (and is typically maximal within 2 hours), so that intensive treatment incurs a real risk of hypotensive overshoots (eg, use of sublingual nifedipine is strongly contraindicated). 71 For this reason, the recommendation (in some of the literature) to prescribe labetalol capsules for home use cannot be supported. It is likely better to opt instead for the administration of a benzodiazepine and to monitor BP. If the severity of the hypertensive episode warrants additional care, the emergency physician treats these cases with the best clinical judgment, taking into consideration the limited duration of the tyramine reaction (eg, considers infusing phentolamine, which has an elimination half-life of only 19 minutes). 8.2.2 The risk of a serious BP increase is limited (owing to improved food standards and increased clarity of dietary guidelines) but cannot be fully ruled out. In severe cases, there is a distinction made between hypertensive urgencies (systolic BP ≥180 mmHg and/or diastolic BP ≥110 mmHg without end-organ VIII Additionally, there is some evidence indicating that cessation of MAOI treatment shortly before surgery may incur the risk of hemodynamic instability, presumably due to incomplete reversal-given the limited timeframe-of various MAOI-induced (neuro)physiological adaptations; we make mention, in this respect, of a case report 91  10 Treatment cessation 10.1 A gradual dose reduction is advised (eg, reduce dose by 10 mg tranylcypromine or 15 mg phenelzine every 2 weeks), certainly after long-term treatment, X in order to prevent (or limit the severity of) withdrawal effects 72,73 -which may include "severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium, and paranoid psychosis," 74 and (hypo) mania. 75 10.2 Following treatment cessation, it is necessary to adhere for at least an additional 2 weeks (longer if an SRI is instated) 76 to the dietary and medication guidelines.
Note: After irreversible inhibition, MAO needs to be regenerated through biosynthesis 77 (and with tranylcypromine, possibly to some extent through biorepair). 35 This process may be marked by a high initial recovery rate that progressively decreases as more MAO is restored. It is generally accepted that sufficient MAO activity is restored after several weeks following treatment cessation to rule out dangerous interactions.

Closing considerations
Classic MAOIs (phenelzine, tranylcypromine, and isocarboxazid) are of potentially life-saving efficacy in the treatment of otherwise intractable depression. Despite this, they are infrequently prescribed, 26 in part because of enduring misinformation regarding their risk profile. The aim of this Prescriber's guide is to provide a practical resource to support practicing physicians in confidently implementing MAOIs into their antidepressant armamentarium, and to ensure that trainee psychiatrists appreciate the distinctive clinical role of MAOIs. 78 Abbreviations BP blood pressure ECT electroconvulsive therapy MAO monoamine oxidase MAOI monoamine oxidase inhibitor SNRI serotonin and norepinephrine reuptake inhibitor SRI serotonin reuptake inhibitor SSRI selective serotonin reuptake inhibitor TCA tricyclic antidepressant attention was given to the Dutch Protocol "Use of classic MAO inhibitors." 20 The recommendations in that Protocol were used as a foundation for this Prescriber's guide, after which some alterations and clarifications, based on modern literature data and increased clinical insight, were made. Additionally, the many research articles published by MAOI Expert Group members, as well as the shared findings from their clinical practice, proved considerable sources of inspiration in writing this guide. The Workgroup is indebted to the following people, be it for their contributions to content/style, or for their endorsement of the guide: John

Disclosures.
A. In general This guide is a best-effort blend of empirical evidence and expert opinion. It is, from an epistemological vantage point, a living document, based on the broad consensus that is both its vice and virtue. This is to say, the process was one of critical reflection and copious revision. Contentious topics are phrased in conditional terms; divisive topics were omitted-overall, the text is better for it. Given the pharmacological complexity, discussions in this Prescriber's guide relating to (side) effects, (contra)indications, and drug-drug interactions are by necessity merely indicative; the enumerations and lists of (co)medications are not exhaustive. X Protracted withdrawal syndromes 92 have been observed following antidepressant cessation (research data pertaining specifically to classic MAOIs are scarce); therefore, some patients may benefit from a very slow, individualized taper (eg, use of incrementally smaller dose decreases to mitigate withdrawal symptoms).
Further research on MAOIs in clinical practice is required so that in subsequent iterations of this guide, the balance of content may shift ever toward greater objectivity (as gleaned from high-quality research studies).
B. Author-specific: Vincent Van den Eynde (first author) is an external research consultant for, and receives or has received consulting fees from: PsychoTropical Research, NeuraWell Therapeutics, and Aristo Pharma GmbH; he has stock options in NeuraWell Therapeutics. He is the only author who received consulting fees (from PsychoTropical Research) specifically for the writing of this guideline.
Wegdan R. Abdelmoemin has nothing to disclose.
Magid M. Abraham has patents (pending; various jurisdictions) for "Compositions and methods for treatment of depression and other disorders"; he is a member of the board of directors for BlackSky Technologies, and for NeuraWell Therapeutics; he is a member of the board of advisors for Qualsight Inc.; he has stocks in NeuraWell Therapeutics. Jay D. Amsterdam receives or has received consulting fees from NeuraWell Therapeutics; he is a member of the Advisory Board for Myrtell.