How to compare doses of different antipsychotics: a systematic review of methods

Background: The ability to calculate equivalent dosage is important when comparing or switching between doses of different antipsychotics in the treatment of schizophrenia. It is also necessary when designing antipsychotic comparator trials which control for dosage.

Method: A systematic review to identify and critically evaluate the methods available for the estimation of antipsychotic dose equivalence was conducted. Electronic searches were carried out using Medline and PubMed and additional information was requested from pharmaceutical companies. The identified methods were evaluated against specific criteria regarding scientific rigour, quality of source data underpinning the method, clinical applicability and utility.

Results: Eleven articles were identified that described methodologies for antipsychotic dose equivalence. Seven of these referred to calculated methods, including chlorpromazine equivalence, maximum dose and daily-defined dose, and relied on an evidence base from both fixed and flexible dosing data. The remaining four described consensus methods which were based on the knowledge and experience of experts. Chlorpromazine was used as the standard comparator drug in the majority of the calculated equivalence studies, whereas risperidone was used for most consensus methods.

Conclusions: Comparison of methods for calculating antipsychotic dose equivalence suggests that different methods yield different equivalencies and the evidence is not sufficiently robust for any of these to be considered as a gold standard method. Thus, choice of method may introduce bias, either an over or underestimate of equivalent dosage, when designing head-to-head, antipsychotic, fixed-dose trials. Consequently, clinical trial reports should routinely include justification of the choice of method for calculating dose equivalence.