To the Editor: We appreciate the comments of Dr. Zullino et al. in regard to the possible interaction of ondansetron with clozapine or olanzapine. We have reviewed the files of all patients who participated in our study, and none was taking atypical antipsychotics. Furthermore, the patients were maintained with stable antipsychotic treatment throughout the study and were not given additional medication on a regular basis. On the basis of the previous information, we believe that the possibility that tardive dyskinesia improved because of a pharmacological intervention other than ondansetron can be discarded.

We cannot exclude the last possibility raised by Dr. Zullino et al., however, regarding a possible interaction of ondansetron and classical neuroleptics at the level of the liver, thus slowing down their disposition and resulting in an elevated antipsychotic plasma level. However, to our knowledge, this hypothesis is not supported by published data on humans. Furthermore, if such an interaction had been of clinical significance, we would have expected worsening of other neuroleptic-induced side effects, such as parkinsonism or somnolence, and those were not observed. Thus, on the basis of current knowledge and the clinical response to ondansetron, we favor a direct effect of ondansetron in alleviating tardive dyskinesia.