Prescribing guide · English summary

How is an MAOI prescribed in practice?

A recent prescribing guide for classic MAOIs was written and endorsed by more than 70 international experts and published open access. Here is a summary of its practical core — designed for the curious patient and the clinician who is (re)discovering these medicines.

Source · Open Access CC-BY 4.0
This page is a summary written by parnate.ch — in our own words, summarising the facts — of the guide: Van den Eynde V, Gillman P. K. et al., “The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression,” CNS Spectrums (Cambridge University Press), 2023;28(4):427–440. Published under a Creative Commons CC-BY 4.0 licence. This is not a reproduction of the original text; in case of doubt, the free original English article is authoritative: read the full guide.

1Who this treatment is for

The guide focuses on treatment-resistant depression — depression that has not responded sufficiently to at least two adequately delivered antidepressant treatments, alone or with augmentation (lithium, for example). Its central message is that, in this situation, MAOIs should always be considered, including in melancholic depression and in so-called “atypical” forms (marked interpersonal sensitivity, mood reactivity, hypersomnia, and so on).

They may remain effective even after electroconvulsive therapy (ECT) or ketamine has failed, and can also be relevant for certain treatment-resistant anxiety disorders and panic disorder. The text brings together a consensus of more than 70 experts, based on six decades of clinical experience.

2The medicines and doses

For tranylcypromine, the starting dose is 10 mg each morning. If the patient does not experience a drop in blood pressure, it may be increased to 20 mg per day. The maintenance dose is between 30 and 60 mg per day in two or three doses: for example, 40 mg at 7 a.m., 10 mg at 10 a.m. and 10 mg at 1 p.m. It is preferable not to take it too late in the day.

For phenelzine, the starting dose is 15 mg three times a day. If the patient feels comfortable, it may be increased to 60 mg per day. The maintenance dose is between 60 and 90 mg per day in two or three doses: for example, 30 mg at 8 a.m., 15 mg at 1 p.m. and 30 mg at 6 p.m.

For older people: a lower initial dose and slower titration. The full antidepressant effect takes time to develop (some improvements in days or weeks, with the full effect later); in treatment-resistant depression, treatment is generally planned for the long term.

As a guide, tranylcypromine may be taken at up to 80–100 mg per day when the patient is properly supervised, but the full antidepressant effect of a given dose may not be reached until after four to six weeks; with phenelzine, this may even take eight to twelve weeks.

3Starting or changing: washout intervals

Before starting an MAOI after a medicine that inhibits reuptake or releases serotonin (an SSRI, SNRI, clomipramine or imipramine, for example), an elimination interval must be observed. The guide calculates it as five times the half-life of the previous medicine — in practice, about eight days for most SSRIs and SNRIs. Two exceptions require more time: 14 days for vortioxetine and, for fluoxetine, generally at least six weeks, sometimes longer after a high dose or prolonged treatment. Between two irreversible MAOIs, the usual interval is 14 days.

As a point of reference, traditional recommendations often use a standard interval of two weeks; the guide refines this rule by relating it to the actual half-life of each medicine. See also our Interactions page.

4Adverse effects and how to manage them

The most consistent effect is orthostatic hypotension (a fall in blood pressure on standing), which is dose-dependent and occurs especially at the start and after an increase — the “low blood pressure” effect of MAOIs.

Phenelzine may cause weight gain, oedema, drowsiness or insomnia, sexual dysfunction, constipation, urinary retention, reduced vitamin B6 (pyridoxine), and, rarely, liver injury.

Tranylcypromine: insomnia, dry mouth, and brief rises in blood pressure after a dose (one to three hours later, often without symptoms, sometimes with palpitations or headache). Management approaches cited by the guide include spreading the dose through the day (to lower peaks), reducing the dose, or using propranolol.

5Interactions & diet

The guide emphasises the same two dangers as our dedicated page: excess serotonin (with serotonergic medicines — SSRIs, SNRIs and clomipramine, but also linezolid and methylene blue, which have “hidden” MAOI activity) and a rise in blood pressure (with stimulants and sympathomimetics). A low-tyramine diet is also required with all classic MAOIs.

→ Interactions & safety → Tyramine diet

6What patients should remember

The guide ends with simple instructions: tell your regular doctor that you take a “classic MAOI”; take no over-the-counter medicine or supplement without asking first (this includes cough syrups and nasal drops); and tell your dentist before any treatment. These points can help start the discussion: see the letter to give to your doctor.

This website provides general information and cannot replace advice from a physician or pharmacist. Do not make any treatment decision without a healthcare professional. MAOIs involve real precautions — dietary and, above all, drug-interaction precautions — which are detailed on the relevant pages.