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Serotonin toxicity and 5-HT2A receptors

Vol. 2, No. 10 / October 2003

I have some thoughts concerning the article by Harvey Sternbach, MD, on serotonin syndrome (Current Psychiatry, May 2003).

Greater emphasis on the 5-HT2A receptor—both in research and treatment—is justified.1 The most recent evidence, which Dr. Sternbach may not have seen at press time, indicates that severe (life-threatening) cases of serotonin toxicity may benefit from 5-HT2A blockers, such as cyproheptadine or chlorpromazine, rather than propranolol.2,3

Based on recent data, it is difficult to confuse neuroleptic malignant syndrome with serotonin toxicity. Thus, administering chlorpromazine in severe cases is rarely a clinical problem.2,4 In one clinical trial, some 80 patients with moderately severe serotonin toxicity were safely and successfully treated with chlorpromazine or cyproheptadine.2

Recent animal studies have also demonstrated the efficacy of 5-HT2A blockers, but not of propranolol.5,6

Knowledge of serotonin toxicity, or serotonin syndrome, has become increasingly important in psychiatry. Readers wishing to remain current should check out a just-published study4 from the toxicology research group led by Ian Whyte, MBBS. The group’s data, from an analysis of 2,222 cases of serotonergic drug poisoning, increase our understanding of serotonin toxicity. Other data presented by Whyte and colleagues3,4 are summarized on my PsychoTropical Research Web site (; some are available by searching PubMed.

P. Ken Gillman, MRC Psych
Consultant and director
Department of clinical neuropharmacology
Pioneer Valley Private Hospital
Mackay, Australia


  1. Gillman PK. Serotonin syndrome: history and risk. Fundam Clin Pharmacol 1998:12:482–91.
  2. Isbister GK, Dawson AH, et al. Comment: serotonin syndrome and 5-HT2A antagonism. Ann Pharmacother 2001;35:1143–4.
  3. Isbister GK, Whyte IM. Serotonin toxicity and malignant hyperthermia: role of 5-HT2 receptors. Br J Anaesth 2002;88:603.
  4. Dunkley E, Isbister G, et al. Hunter serotonin toxicity criteria: a simple and accurate diagnostic decision rule for serotonin toxicity. Q J Med 2003;96:635–42.
  5. Nisijima K, Shioda K, et al. Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int 2003;43:155–64.
  6. Nisijima K, Yoshino T, et al. Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res 2001;890:23–31.

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