cyproheptadine in serotonin syndrome

Q: 42 years old female is admitted to the ICU with probable serotonin syndrome. Cyproheptadine has been initiated. Cyproheptadine is a? - select one

A) histamine-1 receptor agonist

B) histamine-1 receptor antagonist 

Answer: B

Although cyproheptadine continues to have a debatable role in serotonin syndrome (SS) - see reference #3 -, it is universally used as it has relatively benign side effects, such as sedation (which is actually desired in SS), and hypotension, which can be relatively managed easily. Cyproheptadine has three properties. It is a:

• histamine-1 receptor antagonist 
• nonspecific 5-HT1A and 5-HT2A antagonistic (two subtypes of serotonin receptors)
• though weak, but has needed anticholinergic activity

#neurology

#pharmacology

References:

1. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998; 16:615.

2. Prakash S, Patel H, Kumar S, Shah CS. Cyproheptadine in serotonin syndrome: A retrospective study. J Family Med Prim Care. 2024 Apr;13(4):1340-1346. doi: 10.4103/jfmpc.jfmpc_652_23. Epub 2024 Apr 22. PMID: 38827706; PMCID: PMC11142004.

3. Nguyen H, Pan A, Smollin C, Cantrell LF, Kearney T. An 11-year retrospective review of cyproheptadine use in serotonin syndrome cases reported to the California Poison Control System. J Clin Pharm Ther. 2019 Apr;44(2):327-334. doi: 10.1111/jcpt.12796. Epub 2019 Jan 16. PMID: 30650197.