Hydroxyzine

Hydroxyzine (Atarax/Vistaril) is a first-generation antihistamine used for things like itching from allergic/dermatologic conditions and as a sedating/anxiolytic medication (it can make people noticeably drowsy and can potentiate other CNS depressants). FDA Access Data+2FDA Access Data+2 It’s also been subject to safety warnings in some regions because it can prolong the QT interval in higher-risk situations (especially with other QT-prolonging drugs or underlying risk factors). European Medicines Agency (EMA)+1

Mechanistically, hydroxyzine’s main action is histamine H1 receptor inverse agonism in the brain/body, which drives its anti-itch and sedating effects. PubChem It is not an SSRI and doesn’t work by blocking serotonin reuptake; however, it can still intersect with “serotonin pathways” indirectly because pharmacology references describe additional serotonin-receptor antagonism (often discussed around 5-HT2A) and other off-target CNS effects. Wikipedia+1 In PFS/PSSD communities, some people report that hydroxyzine (like many psychoactive meds/sedating antihistamines) can trigger a flare/crash—the plausible reasons are less “SSRI-like serotonin elevation” and more CNS signaling shifts(histamine/serotonin receptor modulation), plus downstream effects on sleep, arousal, and autonomic tone in already-sensitized individuals.

Crash Anecdotes:

https://www.reddit.com/r/PSSD/comments/13icvc4/hydroxyzine_cant_make_pssd_worse_right/

https://www.reddit.com/r/PSSD/comments/17gk129/can_hydroxyzine_cause_this/

My Personal Risk Ranking:

High Risk of Permanent Worsening (for PFS/PSSD/PAS):
If you currently have PFS/PSSD/PAS, this substance may carry a moderate risk of worsening symptoms—potentially in a lasting way—and is best avoided.

Given the uncertainty and the potential severity of outcomes, the risk may not be worth the advertised benefits.