Atypicals Antidepressants
Mirtazapine, trazodone, and vortioxetine are often described as “atypical” or “multimodal” antidepressants, but they still meaningfully affect serotonin and other core CNS signaling systems. Mirtazapine increases norepinephrine and serotonin release primarily via α2-adrenergic blockade and also antagonizes 5-HT2/5-HT3 receptors and H1 histamine receptors (often producing strong sedation and appetite/weight effects). Trazodone is commonly categorized as a SARI (serotonin antagonist/reuptake inhibitor): it antagonizes 5-HT2A receptors and inhibits serotonin reuptake, and it also blocks α1-adrenergic and H1 receptors, which is why it’s frequently used off-label for sleep. Vortioxetine inhibits the serotonin transporter (SERT) and modulates multiple serotonin receptors (often marketed as “multimodal,” but still fundamentally serotonergic). None of these are typically framed as direct anti-androgens; their relevance is primarily via CNS and serotonin-linked effects rather than androgen receptor blockade.
In PFS/PSSD/PAS discussions, these medications are often approached cautiously because they can still produce significant shifts in serotonergic tone and broader arousal/sleep/emotional regulation systems. Even if vortioxetine is sometimes reported in general populations to have lower rates of sexual side effects than classic SSRIs, community anecdotes suggest it does not reliably avoid PSSD/PFS-style sensitivities. Likewise, mirtazapine and trazodone can be destabilizing for some individuals due to combined serotonergic, adrenergic, and antihistamine effects (sleep changes, emotional blunting/anhedonia changes, agitation or “flattening,” and sexual symptom changes are commonly discussed). Overall, these are frequently grouped with other serotonin-active agents as “high-variance” options for sensitized individuals.
Crash Anecdotes:
https://www.reddit.com/r/PSSD/comments/ztt123/vortioxetine_trintellix_victims_here/
https://www.reddit.com/r/PSSD/comments/1ffqnzc/update_mirtazapine_destroyed_me/
https://www.reddit.com/r/PSSD/comments/o0v46z/trazadone/
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 Severe and Sometimes Lasting Worsening (for PFS/PSSD/PAS):
Among individuals who already have PFS/PSSD/PAS, mirtazapine, trazodone, and vortioxetine are commonly mentioned in community reports as preceding symptom worsening, sometimes described as prolonged. Concerns usually focus on sexual symptoms, emotional blunting/anhedonia, sleep disruption, and nervous-system destabilization
Evidence basis: Established pharmacology and interaction literature; mainstream medical safety guidance; anecdotal reports (online forums, self-reports); no controlled studies examining PFS/PSSD/PAS-specific outcomes.