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Is chlorpromazine safe?

Vol. 7, No. 9 / September 2008

I am concerned about a recommended treatment for serotonin syndrome in “Did Internet-purchased diet pills cause serotonin syndrome?” (Current Psychiatry, July 2008) by Drs. Kyoung Bin Im and Jess G. Fiedorowicz. The authors suggest administering the antipsychotic chlorpromazine and cite a case by Gillman1 supporting this indication.

This seems like a particularly risky option because of the overlap in symptomatology between neuroleptic malignant syndrome (NMS) and serotonin syndrome as described by the authors and the fact that administering an additional antipsychotic to a patient with NMS could be fatal. Further, most reports indicate that serotonin syndrome typically is self-limited and best treated with supportive measures and withdrawal of 5-HT active compounds.

Mark Beale, MD
Charleston Psychiatric Associates
Charleston, SC

1. Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol 1997;17(2):128-9.

Drs. Fiedorowicz and Im respond

In 1997, Gillman reported a case of a woman with serotonin syndrome whose condition did not improve with supportive management, cyproheptadine, and propranolol. The patient improved 2 hours after receiving intramuscular chlorpromazine, 50 mg. Chlorpromazine was selected because of its antagonism at both 5-HT1A and 5-HT2A receptors, nearly equipotent to cyproheptadine.1 In 1999 Gillman reviewed case reports for the treatment of serotonin syndrome with chlorpromazine vs cyproheptadine and concluded these 5-HT2 antagonists may be required as a lifesaving measure.2 Since then chlorpromazine has been suggested as part of serotonin syndrome treatment.3,4 High doses of chlorpromazine and cyproheptadine have been shown to reduce death in animal models of serotonin syndrome, an effect mediated by 5-HT2A antagonism.5

We briefly mentioned chlorpromazine as a medical management option for serotonin syndrome, though we did not recommend it in the case presented. We stated that antipsychotics are contraindicated in NMS and in Table 2 (p. 77) illustrated a common treatment strategy that included avoiding antipsychotics.

We share the writer’s concern and hope to reinforce this point. When diagnosis of NMS or serotonin syndrome is unclear, it is advisable to avoid antipsychotics such as chlorpromazine or serotonergic medications such as bromocriptine.

Jess G. Fiedorowicz, MD
Associate in psychiatry

Kyoung Bin Im, MD
Chief resident

Departments of internal medicine and psychiatry
Roy J. and Lucille A. Carver College of Medicine
University of Iowa
Iowa City


1. Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol 1997;17(2):128-9.

2. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13(1):100-9.

3. Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotonergic disorders. Pain Med 2003;4(1):63-74.

4. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352(11):1112-20.

5. Nisijima K, Yoshino T, Yui K, Katoh S. 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(1):23-31.

To comment on articles in this issue or other topics, send letters in care of Erica Vonderheid, Current Psychiatry, 110 Summit Avenue, Montvale, NJ 07645, or click here.

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