2012 APA - IPS: Study Design, Not Efficacy, Is the Key to Conflicting Studies of Schizophrenia Drugs

New York, NY —A poster presented at the American Psychiatric Association 64^th Institute on Psychiatric Services described a study that asked a simple question and provided a fresh perspective with surprising results.

“The question is, do depot medications work better than oral agents in schizophrenia?” said study author Bruce Wong, MD.

In numerous studies comparing the efficacy of depot formulations versus oral antipsychotics for the treatment of schizophrenia, confusing and inconsistent results abound. Dozens of randomized controlled trials, observational studies, and meta-analyses provide evidence that one is superior to the other—or vice versa.

According to the authors, “This raises important practical questions of therapy in managing schizophrenia, but also of how study design should be viewed in comparative effectiveness research and the possible tension between efficacy and effectiveness of medications. In order to reconcile these inconsistencies in results, this study implements a novel approach to systematically account for the effect of study design on the relative efficacy of antipsychotic formulations.”

To find the answer, Wong and colleagues conducted a PubMed literature review targeting all articles from 2000 to 2011 that included the following search terms: schizophrenia; variants of the word injection; depot; long acting; and names of an assortment of antipsychotic agents. To calculate comparable risk ratios, only studies that reported information on relapse, hospitalization, or all-cause discontinuation were included, yielding a total of 416 studies.Further refinementand systematic review of the full text versions resulted in 13 relevant studies, divided into three categories; five randomized controlled trials, four prospective observations, and four retrospective observations, including information on 19 depot-oral comparisons.

A meta-analysis of these found no difference between depot and oral antipsychotic agents in randomized controlled trials. In contrast, in prospective and retrospective observational studies in clinical settings, depot formulations displayed significant advantage.

Looked at from this perspective, the researchers concluded that the disparitywas not attributable to the drugs, but to the design of the studies. Wong explained the conclusion in terms of its applicability to clinical practice.

“It is very clear that if your practice looks like an RCT—that is, if you see the patients very frequently and monitor their medication closely—depot formulations won’t give any advantage,” Wong said.“However, if you prescribe antipsychotics but don’t see patients very often, you will find a better result from depot formulations.”

In addition to raising questions about managing therapy, the study raises important questions about how study design should be viewed in future comparative effectiveness research.

The abstract of this study is available here.