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Letter to the Editor   |    
Ondansetron for Tardive Dyskinesia
DANIELE F. ZULLINO, M.D.; CHIN B. EAP, PH.D.; PIERRE VOIROL, PH.D.
Am J Psychiatry 2001;158:657-a-658. doi:10.1176/appi.ajp.158.4.657-a

To the Editor: We read with great interest the article by Pinkhas Sirota, M.D., and colleagues (1) on the use of ondansetron in the treatment of neuroleptic-induced tardive dyskinesia. The findings are especially remarkable in light of reports on the efficacy of clozapine and olanzapine in treating tardive dyskinesia (2, 3); these drugs having some affinity for the serotonin 5-HT3 receptor.

In the Method section of their article, the authors stated that their patients had received a stable psychotropic drug regimen for at least 6 months before study entry. It would, however, be interesting to know what type of antipsychotics the patients had been receiving, especially if clozapine or olanzapine could have biased the results. It would also be interesting to know if concomitant medications could have induced an increase in plasma concentrations of the given antipsychotics. Increasing a dose of antipsychotics may, although transiently, alleviate tardive dyskinesia.

A literature search by the authors did not reveal any effects of ondansetron on the metabolism of other medications. In vitro studies have, however, shown that ondansetron is a competitive inhibitor of the CYP2D6-dependent O-demethylation of dextromethorphan, with a Ki value of 29 μM, and a competitive inhibitor of the CYP3A4-dependent metabolism of cyclosporine A, with a Ki of 31 μM (4). Pharmacokinetic interactions between ondansetron and antipsychotic drugs, whose metabolism largely depends on CYP2D6 and CYP3A4, cannot therefore be excluded.

Sirota P, Mosheva T, Shabtay H, Giladi N, Korczyn AD: Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia. Am J Psychiatry  2000; 157:287–289
[PubMed]
[CrossRef]
 
Bassitt DP, Louza Neto MR: Clozapine efficacy in tardive dyskinesia in schizophrenic patients. Eur Arch Psychiatry Clin Neurosci  1998; 248:209–211
[PubMed]
[CrossRef]
 
Raja M, Azzoni A, Maisto G: Three cases of improvement of tardive dyskinesia following olanzapine treatment. Int J Neuropsychopharmacol  1999; 2:333–334
[PubMed]
[CrossRef]
 
Fischer V, Vickers AE, Heitz F, Mahadevan S, Baldeck JP, Minery P, Tynes R: The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab Dispos  1994; 22:269–274
[PubMed]
 
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References

Sirota P, Mosheva T, Shabtay H, Giladi N, Korczyn AD: Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia. Am J Psychiatry  2000; 157:287–289
[PubMed]
[CrossRef]
 
Bassitt DP, Louza Neto MR: Clozapine efficacy in tardive dyskinesia in schizophrenic patients. Eur Arch Psychiatry Clin Neurosci  1998; 248:209–211
[PubMed]
[CrossRef]
 
Raja M, Azzoni A, Maisto G: Three cases of improvement of tardive dyskinesia following olanzapine treatment. Int J Neuropsychopharmacol  1999; 2:333–334
[PubMed]
[CrossRef]
 
Fischer V, Vickers AE, Heitz F, Mahadevan S, Baldeck JP, Minery P, Tynes R: The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab Dispos  1994; 22:269–274
[PubMed]
 
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