Methodological Concerns in a Trial of Ziprasidone and Olanzapine

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Back to table of contents Previous article Next article Letter to the EditorFull AccessMethodological Concerns in a Trial of Ziprasidone and OlanzapineDAVID E. ROSS, M.D., DAVID E. ROSSSearch for more papers by this author, M.D., Richmond, Va.Published Online:1 Jul 2005https://doi.org/10.1176/appi.ajp.162.7.1391-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: I read with interest the study by Dr. Simpson and colleagues comparing ziprasidone to olanzapine for the treatment of schizophrenia. I commend the authors for completing a head-to-head study that provides some important safety data. However, the study has two important limitations that limit its interpretation.First, the olanzapine dosing was excessively restricted with respect to the upward titration rate (5 mg/day on days 1 and 2; 10 mg/day on days 3–7) and the maximum dose allowed (15 mg/day). The authors’ argument that this dosing schedule is consistent with the package insert is weak. This dosing schedule falls within the low range of the guidelines on the package insert, which was based on studies performed about 10 years ago and submitted for approval to the Food and Drug Administration. Since that time, there have been many more studies and a vast amount of clinical experience to suggest that a significantly faster upward titration rate and a higher maximum dose often are needed to adequately treat acutely ill schizophrenia patients (1). Therefore, the approach chosen by the authors was biased against finding efficacy in the olanzapine group.Second, the vast majority of patients in both groups were treated with lorazepam in addition to the antipsychotic. Why were such high rates of lorazepam allowed? Granted, acutely psychotic patients often benefit from a benzodiazepine. But because a major goal of the study was to compare the efficacy of ziprasidone versus olanzapine, then the high rate of use of lorazepam limited the interpretation of the results. Benzodiazepines help to enhance sleep and reduce agitation and anxiety, thus interfering with the interpretations regarding efficacy of the antipsychotics. Furthermore, benzodiazepines suppress antipsychotic-induced movement disorders such as akathisia, thus limiting the interpretation of the results regarding these adverse events.In summary, this was not simply a study of ziprasidone versus olanzapine; it was a study of ziprasidone plus lorazepam versus suboptimally dosed olanzapine plus lorazepam.Reference1. Kinon BJ, Ahl JSV, Hill AL, Buckley PF: Dose response and atypical antipsychotics in schizophrenia. CNS Drugs 2004; 18:597–616Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByZiprasidone versus other atypical antipsychotics for schizophrenia7 October 2009 | Cochrane Database of Systematic Reviews, Vol. 5 Volume 162Issue 7 July 2005Pages 1391-a-1391 Metrics PDF download History Published online 1 July 2005 Published in print 1 July 2005