title: Dose response and atypical antipsychotics in schizophrenia.
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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Kinon
authors.forename: Jonna
authors.initials: J
authors.lastname: Ahl
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Stauffer
authors.forename: Angela L
authors.initials: AL
authors.lastname: Hill
authors.forename: Peter F
authors.initials: PF
authors.lastname: Buckley
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents