Cyproheptadine
Cyproheptadine (Periactin) is a first-generation antihistamine used for allergy symptoms, and it is also used off-label for appetite stimulation and, in some settings, as part of management for serotonin toxicity. Pharmacologically, it acts as a histamine H1 antagonist and a serotonin receptor antagonist (commonly discussed around 5-HT2), and it also has anticholinergic and sedating properties. Common effects include sleepiness, dry mouth or constipation, and increased appetite or weight gain.
In the context of PFS/PSSD/PAS, cyproheptadine is often described as controversial. Some individuals report benefit—often attributed to blocking certain serotonin receptor signaling and altering arousal or sleep patterns—while others report flares or crashes after use. Community discussions commonly suggest that these mixed outcomes may relate to the drug’s broad CNS effects, including strong sedation, anticholinergic load, and multi-receptor activity, which can be destabilizing for sensitized individuals. It is generally not viewed as a reliable treatment for these conditions, and experimentation during unstable periods is often approached cautiously.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/087056s045lbl.pdf
https://pmc.ncbi.nlm.nih.gov/articles/PMC9922522/
Crash Anecdotes (Community Reports):
https://www.reddit.com/r/PSSD/comments/1ay0fwe/be_careful_with_cyproheptadine/
https://www.reddit.com/r/PSSD/comments/1bk4o8i/cyproheptadine_warning/
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, Including Flares (for PFS/PSSD/PAS):
Among individuals who already have PFS/PSSD/PAS, cyproheptadine is occasionally to commonly mentioned in community reports as producing noticeable changes—sometimes described as improvement, and sometimes as a flare or crash. Reports of worsening often focus on excessive sedation, emotional flattening, cognitive dulling, or a general sense of destabilization after initiation or dose changes. Because responses appear highly individual and difficult to predict, many in these communities treat cyproheptadine as a moderate-risk, high-variance option rather than a dependable intervention.
For individuals without these conditions, cyproheptadine is a well-known sedating antihistamine and is often tolerated, though anticholinergic and sedative side effects can still be significant. Given the uncertainty and variability described in anecdotes, some people with PFS/PSSD/PAS choose cautious, medically guided use only when there is a clear indication, rather than experimenting during stabilization.
Evidence basis: FDA labeling and established pharmacology; mechanistic literature; anecdotal reports (online forums, self-reports); no controlled studies examining PFS/PSSD/PAS-specific outcomes.