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 ac...

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Bibliographic Details
Published in:CNS drugs 2004-01, Vol.18 (9), p.597-616
Main Authors: KINON, Bruce J, AHL, Jonna, STAUFFER, Virginia L, HILL, Angela L, BUCKLEY, Peter F
Format: Article
Language:English
Subjects:
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - adverse effects
Antipsychotic Agents - therapeutic use
Biological and medical sciences
Clinical Trials as Topic
Dose-Response Relationship, Drug
Humans
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Schizophrenia - drug therapy
Treatment Outcome
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Summary: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.
ISSN:1172-7047
1179-1934
DOI:10.2165/00023210-200418090-00005