Switching to Olanzapine After Unsuccessful Treatment With Risperidone During the First Episode of Schizophrenia: An Open-Label Trial

Hitoshi Takahashi, M.D., Ph.D.; Mitsuhiro Kamata, M.D., Ph.D.; Keizo Yoshida, M.D., Ph.D.; Jun Ishigooka, M.D., Ph.D.; and Hisashi Higuchi, M.D., Ph.D.

Background: The efficacy and safety of switching to olanzapine were investigated in patients with first-episode schizophrenia who failed to attain an adequate clinical response to an initial therapeutic trial of risperidone (2-6 mg/day for 12 weeks).

Method: A total of 58 first-episode patients with DSM-IV schizophrenia who had residual symptoms following treatment with risperidone were enrolled in an open-label, 12-week study of olanzapine. Dosing was determined by clinical judgment. The main efficacy measure was the Brief Psychiatric Rating Scale (BPRS). Patients with a 20% or greater decrease in BPRS total score plus a final Clinical Global Impressions-Severity of Illness scale score of <= 3 (mildly ill) were considered responders. The study was conducted from April 2001 to March 2005.

Results: Fifty-one patients completed the study, and 7 discontinued due to side effects and medication noncompliance. The mean dosage of olanzapine was 15.3 (SD 4.2) mg/day at study endpoint. Total BPRS scores significantly decreased (12.3%) during olanzapine treatment (p < .001). In addition, BPRS subscales of anxiety/depression and excitement significantly decreased (19.1% and 29.5%, respectively; p < .001). The responder rate was 29.3% (17/58). BPRS positive symptom subscale score at baseline was significantly higher in nonresponders compared to responders (p < .001). Comparison of percentage change in BPRS total scores between responders and nonresponders revealed a significant difference at week 4 that continued until study endpoint (p < .001). Of 58 patients, 27 (46.6%) showed clinically significant weight gain (>= 7%) from baseline.

Conclusion: Although we cannot draw any conclusion from a study without a control group, favorable outcomes and good tolerance were observed after switching to olanzapine from risperidone in our population. In addition, factors that predicted a good overall response included a relative absence of positive symptoms at baseline and the percentage reduction in total BPRS score at 4 weeks of treatment. Double-blind, crossover trials are needed to confirm these observations.

(J Clin Psychiatry 2006;67:1577-1582)

Received March 26, 2006; accepted May 10, 2006. From the Yuri Kumiai General Hospital, Honjoh, Akita (Drs. Takahashi and Kamata); the Department of Psychiatry, Nagoya University School of Medicine, Nagoya, Aichi (Dr. Yoshida); the Department of Psychiatry, Tokyo Women's Medical University, Tokyo (Dr. Ishigooka); and Omagari City Hospital, Daisen, Akita (Dr. Higuchi), Japan.

This study did not receive any financial or material support.

The authors report no financial or other relationship relevant to the subject of this article.

The authors thank Andrew H. Miller, M.D., and Charles L. Raison, M.D., for their assistance with manuscript preparation.

Corresponding author and reprints: Hitoshi Takahashi, M.D., Yuri Kumiai General Hospital, 38 yago, kawaguchi, Honjoh, Akita, 015-8511, Japan (e-mail: takahashi_h1969@yahoo.co.jp).