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

Leucht, Stefan
Samara, Myrto
Heres, Stephan
Patel, Maxine X.
Woods, Scott W.
Davis, John M.

¹Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany
²Department of Psychiatry, University of Oxford, Oxford, UK
³Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
⁴Department of Psychiatry, Yale University School of Medicine, New Haven, CT
⁵Connecticut Mental Health Center, New Haven, CT
⁶Psychiatric Institute, University of Illinois at Chicago, Chicago, IL
⁷Maryland Psychiatric Research Center, Baltimore, MD

^*To whom correspondence should be addressed; Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; tel: +49-89-4140-4249, fax: +49-89-4140-4888, e-mail: [email protected]

Schizophrenia Bulletin 40(2):p 314-326, March 2014. | DOI: 10.1093/schbul/sbu001

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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.