Dose response and atypical antipsychotics in schizophrenia.
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.
Kinon
Bruce J
BJ
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285, USA.
Ahl
Jonna
J
Stauffer
Virginia L
VL
Hill
Angela L
AL
Buckley
Peter F
PF
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents