MAOIs

MAOIs (monoamine oxidase inhibitors) are antidepressants that work by blocking the monoamine oxidase enzymes (MAO-A and/or MAO-B) that normally break down neurotransmitters like serotonin, norepinephrine, and dopamine—so levels/signaling of these monoamines increase (1). The “classic” MAOIs (like phenelzine and tranylcypromine) can be very effective for certain kinds of depression, but they come with important safety constraints: dietary tyramine restrictions and careful avoidance of interacting drugs because of rare but serious risks like hypertensive crisis and serotonin syndrome (2). Phenelzine also has a notable additional mechanism: it can inhibit GABA-transaminase, which can increase brain GABA (one reason some people experience a distinct calming/anxiolytic effect) (3).

For PFS/PSSD/PAS, MAOIs aren’t typically discussed as “anti-androgenic.” The main overlap is that MAOIs can strongly shift serotonin/dopamine/norepinephrine tone (and sometimes GABA, depending on the MAOI), which in sensitized people may flare symptoms—for example, changes in anhedonia, anxiety, sleep, or emotional blunting. There isn’t solid clinical evidence that MAOIs consistently worsen PFS/PSSD, but because they can be powerful and have major interaction risks, the safest framing is “variable responses; proceed cautiously; and work with a clinician who understands these syndromes and MAOI safety.” (4).

(1) https://www.ncbi.nlm.nih.gov/books/NBK557395/

(2) https://www.mayoclinic.org/diseases-conditions/depression/in-depth/maois/art-20043992

(3) https://pubmed.ncbi.nlm.nih.gov/17768678/

(4) https://www.ncbi.nlm.nih.gov/books/NBK539848/

Crash Anecdotes:

https://www.reddit.com/r/PSSD/comments/18hepja/maois_what_are_your_thoughts_and_experiences/

My Personal Risk Ranking:

Moderate Risk of Permanent Worsening (for PFS/PSSD/PAS):
If you have PFS/PSSD/PAS, MAOIs are generally viewed as a moderate-risk option for potential longer-lasting worsening—though many people consider them less risky than SSRIs/SNRIs. Personally, I tried Parnate (tranylcypromine): it eventually eliminated my anxiety, but the trade-off was brutal anhedonia that has persisted for me. It did not worsen sexual symptoms in my case.