MAOIs are for true treatment-resistant depression and end-of-the-road anxiety, used by clinicians who are experienced or well supervised. The main safety issue is hypertensive crisis with tyramine in food. Some argue they are the most effective antidepressants and deserve a trial earlier than they usually get.
When we reach for it
Consider MAOIs (and TCAs) for true treatment-resistant depression, if you know what you are doing. Not for depression that is really driven by trauma and personality.
“Consider them if you have true treatment-resistant depression, not just we're calling something that's trauma and personality depression. Please consider your TCAs and your MAOIs if you know what you're doing”
1:08:17Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 In our practice they are reserved for patients who have failed even the combination of an SSRI and a second-generation antipsychotic.
“reserve the use, in my practice anyway, to patients who have failed even the SSRI and second-generation antipsychotic combo”
49:28Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 If you are an experienced clinician, or under good supervision, and you have reached the end of the road of medications for a patient's anxiety, do not be shy about considering an MAOI. The same goes for depression.
“don't be shy if you are an experienced or under good supervision clinician and you're reaching the end of the road of pharmacological agents for anxiety for a patient. You can consider an MAOI. Same thing for your depression patients, right”
41:14Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025
Side effects and safety
The problem with MAOIs is the risk of a hypertensive crisis with foods containing tyramine, and many of the best foods (the ones at a wine party) have some.
“MAOIs, the problem is that you have a risk for a hypertensive crisis with certain foods. Dr. Malzberg, it is tyramine. Tyramine. And in a way, all the best foods have this to some extent at a wine party”
48:27Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025
Pearls
One view we have discussed holds that MAOIs are, point blank, the most effective antidepressants, and that instead of switching medications again and again, these patients deserve an MAOI trial earlier in the algorithm.
“he views these medications as like point blank, the most effective antidepressants and thinks that we reach for other medications. We keep switching other medications when these patients deserve a trial of MAOIs earlier in the treatment algorithm”
50:59Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025
Pitfalls and myths
Before going past the standard options for anxiety, make sure you really need to: do more re-diagnosis, formulation work and lifestyle change first.
“S through B tier stuff, You really need it. Doing more re-diagnosis And, uh, work. Working on formulation and lifestyle changes, et cetera, et cetera”
1:01:01Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026
From these episodes
- Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 · 1 point
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 1 point
- Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 · 1 point
- Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 · 3 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.