Switching to olanzapine after unsuccessful treatment with risperidone during the first episode of schizophrenia: an open-label trial

J Clin Psychiatry. 2006 Oct;67(10):1577-82. doi: 10.4088/jcp.v67n1013.


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 <or= 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 (>or= 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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / therapeutic use
  • Brief Psychiatric Rating Scale / statistics & numerical data
  • Cross-Over Studies
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Male
  • Olanzapine
  • Prognosis
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Risperidone / therapeutic use*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Severity of Illness Index
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Risperidone
  • Olanzapine