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Letters

Ziprasidone — not an option for serotonin syndrome

Marshall E. Cates
CMAJ November 25, 2003 169 (11) 1147-1148;
Marshall E. Cates
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A recent article concerning serotonin syndrome1 contained an inaccuracy that might result in clinicians attempting a misguided, if not fatal, treatment option. While correctly noting the presumed role of 5-HT1A receptor activation in the pathophysiology of the syndrome, the authors twice surmise that ziprasidone, an atypical antipsychotic, might warrant study as a therapeutic option because of its potent blockade of 5-HT1A receptors.

The reference that the authors use as the pharmacologic basis for this assertion does acknowledge the potent binding of ziprasidone at the 5-HT1A receptor;2 however, the high affinity of the drug for this receptor is as an agonist, not as an antagonist.3,4 Other effects of ziprasidone on the serotonergic system include potent antagonism of 5-HT1D, 5-HT2A and 5-HT2C receptors, as well as moderate inhibition of serotonin reuptake.3,4

The net result of ziprasidone on serotonergic neurotransmission makes it an inappropriate candidate for treating serotonin syndrome. Aside from the overt problem of directly stimulating 5-HT1A receptors, there is also the more subtle, yet still concerning, matter of indirectly stimulating these same receptors via antagonism of 5-HT2A receptors and inhibition of serotonin reuptake. In fact, there have been reported cases of serotonin syndrome precipitated by the use of other atypical antipsychotics, which are also 5-HT2A receptor antagonists, in combination with serotonergic drugs.5

Thus, the use of ziprasidone for treatment of serotonin syndrome seems ill-advised and could prolong or worsen the patient's symptoms. In cases in which the clinician seeks treatment with serotonin antagonists, purported options include methysergide, cyproheptadine and propranolol.6

Marshall E. Cates Associate Professor of Pharmacy Practice Samford University McWhorter School of Pharmacy Tuscaloosa, Ala.

Footnotes

  • Competing interests: None declared.

References

  1. 1.↵
    Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ 2003;168(11):1439-42.
    OpenUrlFREE Full Text
  2. 2.↵
    Richelson E, Souder T. Binding of antipsychotic drugs to human brain receptors. Focus on newer generation compounds. Life Sci 2000;68:29-39.
    OpenUrlCrossRefPubMed
  3. 3.↵
    Green B. Focus on ziprasidone. Curr Med Res Opin 2001;17:146-50.
    OpenUrlCrossRefPubMed
  4. 4.↵
    Carnahan RM, Lund BC, Perry PJ. Ziprasidone, a new atypical antipsychotic drug. Pharmacotherapy 2001;21:717-30.
    OpenUrlCrossRefPubMed
  5. 5.↵
    Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry 2002;159:672-73.
    OpenUrlCrossRefPubMed
  6. 6.↵
    Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705-13.
    OpenUrlPubMed
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Canadian Medical Association Journal: 169 (11)
CMAJ
Vol. 169, Issue 11
25 Nov 2003
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Ziprasidone — not an option for serotonin syndrome
Marshall E. Cates
CMAJ Nov 2003, 169 (11) 1147-1148;

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