Dose Equivalents for Second-Generation Antipsychotics: The Minimum Effective Dose Method

Authors:
  • MSM. Samara
    M. Samara
  • SHS. Heres
    S. Heres
  • MPM. X. Patel
    M. X. Patel
  • SWS. W. Woods
    S. W. Woods
  • JDJ. M. Davis
    J. M. Davis
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Abstract
Clinicians need to know the right antipsychotic dose for optimized treatment, and the concept of dose equivalence is important for many clinical and scientific purposes. We refined a method presented in 2003, which was based on the minimum effective doses found in fixed-dose studies. We operationalized the selection process, updated the original findings, and expanded them by systematically searching more recent literature and by including 13 second-generation antipsychotics. To qualify for the minimum effective dose, a dose had to be significantly more efficacious than placebo in the primary outcome of at least one randomized, double-blind, fixed-dose trial. In a sensitivity analysis, 2 positive trials were required. The minimum effective doses identified were subsequently used to derive olanzapine, risperidone, haloperidol, and chlorpromazine equivalents. We reviewed 73 included studies. The minimum effective daily doses/olanzapine equivalents based on our primary approach were: aripiprazole 10 mg/1.33, asenapine 10 mg/1.33, clozapine 300 mg/40, haloperidol 4 mg/0.53, iloperidone 8 mg/1.07, lurasidone 40 mg/5.33, olanzapine 7.5 mg/1, paliperidone 3 mg/0.4, quetiapine 150 mg/20, risperidone 2 mg/0.27, sertindole 12 mg/1.60, and ziprasidone 40 mg/5.33. For amisulpride and zotepine, reliable estimates could not be derived. This method for determining antipsychotic dose equivalence entails an operationalized and evidence-based approach that can be applied to the various antipsychotic drugs. As a limitation, the results are not applicable to specific populations such as first-episode or refractory patients. We recommend that alternative methods also be updated in order to minimize further differences between the methods and risk of subsequent bias.

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