MAOIs
MAOIs (monoamine oxidase inhibitors) are antidepressants that work by inhibiting monoamine oxidase enzymes (MAO-A and/or MAO-B), which normally break down neurotransmitters such as serotonin, norepinephrine, and dopamine—so monoamine signaling increases. Classic MAOIs (e.g., phenelzine, tranylcypromine) can be highly effective for certain forms of depression, but they come with important safety requirements: dietary tyramine restriction and careful avoidance of interacting medications due to rare but serious risks such as hypertensive crisis and serotonin syndrome. Phenelzine also has an additional mechanism discussed in the literature—GABA-transaminase inhibition—which can increase brain GABA and may contribute to anxiolytic effects in some users.
In PFS/PSSD/PAS discussions, MAOIs are not typically framed as anti-androgenic. The main relevance is that MAOIs can substantially shift monoamine tone (and in some cases GABA), which may affect anxiety, sleep, anhedonia/emotional blunting, and overall nervous-system stability—areas that are often already sensitive in these conditions. There is not strong clinical evidence that MAOIs consistently worsen PFS/PSSD/PAS, but given their potency and interaction risks, community discussions often emphasize that responses can be variable and that any MAOI use should be approached cautiously and under experienced medical supervision.
(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 (Community Reports):
https://www.reddit.com/r/PSSD/comments/18hepja/maois_what_are_your_thoughts_and_experiences/
How to Interpret This Page
This page summarizes anecdotal reports and community observations, not medical evidence. “Risk” here refers to how frequently severe or prolonged symptom worsening is reported, not to proven causation or population-wide probability. Individual responses vary widely, and absence of issues in some users does not rule out significant reactions in others.
Risk Signal Based on User Reports
Reports of Variable Outcomes (for PFS/PSSD/PAS):
Among individuals who already have PFS/PSSD/PAS, MAOIs are discussed less often than SSRIs/SNRIs as triggers of severe worsening, but they are still described as potentially destabilizing for some users—especially around anxiety, sleep, emotional blunting, and anhedonia. Because MAOIs can produce strong neurochemical shifts and have significant interaction constraints, many in these communities view them as a higher-complexity option best reserved for situations where the expected benefit is substantial and the prescriber is experienced with MAOI safety.
For individuals without these conditions, MAOIs are effective for some people but require careful dietary and medication interaction management. As with any potent psychiatric medication, adverse mood/anxiety/sleep effects can occur in a subset of users, particularly during initiation or dose changes.
Personal note (anecdotal): You reported that tranylcypromine (Parnate) eventually eliminated anxiety for you, but you experienced a difficult anhedonia trade-off that persisted, and you did not notice worsening of sexual symptoms in your case.
Evidence basis: Established pharmacology and clinical safety guidance for MAOIs; anecdotal reports (online forums, self-reports); no controlled studies examining PFS/PSSD/PAS-specific outcomes.