Dose response and atypical antipsychotics in schizophrenia

CNS Drugs. 2004;18(9):597-616. doi: 10.2165/00023210-200418090-00005.

Abstract

Based on information from clinical trials, both the efficacy and adverse effects of conventional antipsychotics in the treatment of schizophrenia are dose related. The overlapping nature of these dose-response profiles limits the use of these agents. Atypical antipsychotics provide greater relief across the comorbid symptom domains of schizophrenia, but dose-response studies and clinical experience have revealed that some of these drugs also have dose limitations. This article reviews the dose-response relationships of the atypical antipsychotics as presented predominantly in pivotal, randomised studies (double-blind and otherwise). Limited data indicate that clozapine shows dose-related efficacy up to 600 mg/day in patients with treatment-resistant schizophrenia. However, higher dosages of clozapine may be associated with the risk of seizures. Risperidone demonstrates dose-related adverse events that compromise efficacy. The dose-response relationships for ziprasidone, quetiapine and aripiprazole are less well established. The efficacy of olanzapine appears to be dose related within the recommended dosage range of 10-20 mg/day, but clinical trials that have explored higher dosages suggest improved efficacy. Furthermore, the higher doses are not associated with a significantly increased incidence of adverse events. Further studies are clearly needed to fully characterise the dose-response relationships of atypical antipsychotics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Humans
  • Schizophrenia / drug therapy*
  • Treatment Outcome

Substances

  • Antipsychotic Agents