Comparison of Treatment-Emergent Extrapyramidal Symptoms in Patients With Bipolar Mania or Schizophrenia During Olanzapine Clinical Trials

Patrizia A. Cavazzoni, M.D.; Paul H. Berg, M.S.; Ludmila A. Kryzhanovskaya, M.D., Ph.D.; Susan D. Briggs, Ph.D.; Tamra E. Roddy, M.S.; Mauricio Tohen, M.D., Dr.P.H.; and John M. Kane, M.D.

Background: Previous research on pharmacotherapy with conventional antipsychotics has suggested that patients with affective disorders have higher rates of treatment-emergent extrapyramidal symptoms (EPS) than patients with schizophrenia. It is not known whether this differential vulnerability holds true for treatment with atypical antipsychotics such as olanzapine. The present analysis retrospectively examined olanzapine clinical trial data for incidence of treatment-emergent EPS in patients with either schizophrenia or bipolar disorder.

Method: Study participants were 4417 patients meeting DSM-III or DSM-IV criteria for either schizophrenia or bipolar mania participating in olanzapine clinical trials through July 31, 2001. Data were pooled across haloperidol-controlled trials and separately across placebo-controlled trials. Measures of EPS included rates of treatment-emergent EPS adverse event by type (i.e., dystonic, parkinsonian, or residual), Simpson-Angus Scale score mean change, rates of treatment-emergent parkinsonism, and rates of anticholinergic use.

Results: Consistent with prior research, haloperidol-treated patients with bipolar disorder appeared to be more vulnerable to the development of EPS than those with schizophrenia. However, olanzapine-treated patients with bipolar disorder were no more likely to develop EPS than those with schizophrenia.

Conclusion: Results support previous research regarding conventional antipsychotics and suggest that olanzapine therapy does not increase the risk of EPS for patients with bipolar disorder.

(J Clin Psychiatry 2006;67:107-113)

Received September 10, 2004; accepted July 6, 2005. From Lilly Research Laboratories, Indianapolis, Ind. (Drs. Cavazzoni, Kryzhanovskaya, Briggs, and Tohen, Mr. Berg, and Ms. Roddy); the Department of Psychiatric Medicine, University of Virginia, Charlottesville (Dr. Kryzhanovskaya); the Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, Mass. (Dr. Tohen); and the Department of Psychiatry, the Zucker Hillside Hospital and the Albert Einstein College of Medicine, Glen Oaks, N.Y. (Dr. Kane).

This work was supported by Eli Lilly and Company. Drs. Cavazzoni, Kryzhanovskaya, Briggs, and Tohen, Mr. Berg, and Ms. Roddy are employees of Eli Lilly and Company.

Portions of these data were presented at the 11th Congress of the Association of European Psychiatrists, May 4-8, 2002, Stockholm, Sweden; the 23rd Congress of the Collegium Internationale Neuropsychopharmacologicum, June 23-27, 2002, Montreal, Canada; and the 15th Congress of the European College of Neuropsychopharmacology, October 5-9, 2002, Barcelona, Spain.

Dr. Kane is a consultant to and has received honoraria from Abbott, Pfizer, Eli Lilly, Janssen, Bristol-Myers Squibb, and AstraZeneca. Drs. Cavazzoni, Kryzhanovskaya, Briggs, and Tohen, Mr. Berg, and Ms. Roddy report no additional financial or other relationships relevant to the subject of this article.

Data for the current analysis were obtained from a total of 18 olanzapine clinical trials conducted by Eli Lilly and Company. A complete list of study codes may be obtained by contacting the corresponding author. The authors wish to acknowledge Christopher Carlson, Ph.D., and Angela R. Evans, Ph.D., for their contribution to the development of this project, and Hank Wei, M.S., for statistical consultation.

Corresponding author and reprints: Patrizia Cavazzoni, M.D., Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285 (e-mail: p_cavazzoni@lilly.com).