• Emily King and Joe A Rotella.
• Melbourne Medical School, Melbourne, Victoria, Australia.
• Emerg Med Australas. 2025 Feb 1; 37 (1): e14554e14554.

AbstractSerotonin toxicity is a potentially fatal condition caused by increased serotonergic activity in the central nervous system. Cyproheptadine, a serotonergic antagonist, is recommended for treatment; however, there is a lack of evidence to support its use. The present study aimed to evaluate the evidence for the use of cyproheptadine in the management of serotonin toxicity following deliberate self-poisoning. Publications from 2003 were identified by searching electronic databases Cochrane, MEDLINE, EMBASE and PsycINFO. The inclusion criteria for studies to be included were determined a priori and consisted of studies published in English (or where an English translation was available) where the primary diagnosis of serotonin toxicity (or syndrome) following deliberate self-poisoning and cyproheptadine was administered as the sole serotonergic antagonist. Studies were evaluated for quality and risk of bias. Twelve articles were identified, of which 11 were case reports and one was a case series. Serotonin toxicity was most attributed to selective serotonin reuptake inhibitors and all cases fulfilled Hunter serotonin toxicity criteria. Cyproheptadine regimen varied widely with respect to reporting of initial dose, repeat doses, frequency and duration. Few reports commented on clinical resolution and therefore efficacy was not established. All studies were graded as being of very low evidence and at high risk of bias. There is a lack of evidence to support the efficacy of cyproheptadine or its recommendation in clinical guidelines pertaining to the management of serotonin toxicity.© 2025 Australasian College for Emergency Medicine.

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