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

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(10):1577-1582