How Dosing Might Influence the Conclusion in an Antipsychotic Polypharmacy Effectiveness Trial
Abstract
Glostrup, Denmark TO THE EDITOR: In the July 2011 issue of the Journal, Susan M. Essock et al. (1) provided valuable information on an important clinical paradox: the widespread use of antipsychotic polypharmacy in the treatment of schizophrenia, despite the lack of evidence to support it. However, the study had an essential limitation that was not addressed in the article: the matter of dosing. The total daily dose of antipsychotic drugs at baseline was comparable between groups, as shown in Table 1 of the article. The total dosage at 6 months follow-up and at treatment discontinuation (for those discontinuing before 6 months) was not reported in the article, but it is highly likely that this dosage was significantly lower in the monotherapy group because one of the prescribed antipsychotics had been discontinued (medication dosing was not constrained by the protocol). If this was the case, there was a bias favoring the polypharmacy group with regard to effectiveness. This is emphasized by the fact that all the study participants had residual symptoms and were candidates for change of medication. Decreasing the total dosage of antipsychotic drugs (as is the most probable scenario in the switch to monotherapy group) in