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Dose Response and Atypical Antipsychotics in Schizophrenia

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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.

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Acknowledgements

This work was funded by Eli Lilly and Company, Indianapolis, IN, USA. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, Indiana, 46285, USA

    Bruce J. Kinon, Jonna Ahl, Virginia L. Stauffer & Angela L. Hill

  2. Department of Psychiatry, Medical College of Georgia, Augusta, Georgia, USA

    Peter F. Buckley

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Kinon, B.J., Ahl, J., Stauffer, V.L. et al. Dose Response and Atypical Antipsychotics in Schizophrenia. CNS Drugs 18, 597–616 (2004). https://doi.org/10.2165/00023210-200418090-00005

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