Antipsychotic response in first-episode schizophrenia: efficacy of high doses and switching

Eur Neuropsychopharmacol. 2013 Sep;23(9):1017-22. doi: 10.1016/j.euroneuro.2013.04.010. Epub 2013 May 22.


Clinicians treating schizophrenia routinely employ high doses and/or antipsychotic switching to achieve response. However, little is actually known regarding the value of these interventions in early schizophrenia. Data were gathered from a treatment algorithm implemented in patients with first-episode schizophrenia that employs two antipsychotic trials at increasing doses before clozapine. Patients were initially treated with either olanzapine or risperidone across three dose ranges, (low, full, high), and in the case of suboptimal response were switched to the alternate antipsychotic. We were interested in the value of (a) high dose treatment and (b) antipsychotic switching. A total of 244 patients were evaluated, with 74.5% (184/244) responsive to Trial 1, and only 16.7% (10/60) responsive to Trial 2. Percentage of response for subjects switched from olanzapine to risperidone was 4.0% (1/25) vs. 25.7% (9/35) for those switched from risperidone to olanzapine. High doses yielded a 15.5% response (14.6% for risperidone vs. 16.7% for olanzapine).The present findings concur with other research indicating that response rate to the initial antipsychotic trial in first-episode schizophrenia is robust; thereafter it declines notably. In general, the proportion of responders to antipsychotic switching and high dose interventions was low. For both strategies olanzapine proved superior to risperidone, particularly in the case of antipsychotic switching (i.e. risperidone to olanzapine vs. vice versa). It remains to be established whether further antipsychotic trials are associated with even greater decrements in rate of response. Findings underscore the importance of moving to clozapine when treatment resistance has been established.

Keywords: Antipsychotic dosing; Antipsychotic switching; Antipsychotic trials; First-episode schizophrenia; Treatment algorithm.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / administration & dosage*
  • Benzodiazepines / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Substitution / methods*
  • Female
  • Humans
  • Male
  • Olanzapine
  • Risperidone / administration & dosage*
  • Schizophrenia / diagnosis*
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • Treatment Outcome
  • Young Adult


  • Antipsychotic Agents
  • Benzodiazepines
  • Risperidone
  • Olanzapine