Objective: Differences in dosing may influence results of pharmaceutical industry–sponsored medication trials. This study aims to determine the relationship between sponsorship and antidepressant dosing and efficacy in randomized controlled trials for major depressive disorder.
Data Sources: Trials were identified through English-language searches of MEDLINE and PsycINFO (January 1996–June 2010) using specific drug names and classes and depressive disorder or major depression and double blind or double-blind method. Other limitations included human subjects and treatment study designs using the clinical queries option. Other sources were also searched following a strict set of inclusion and exclusion criteria.
Study Selection: Randomized controlled trials were included if they examined antidepressant treatment for major depressive disorder, reported mean final medication dosages, acknowledged an association with industry, and included study arms of medications produced by the associated manufacturer and a competitor (“sponsor” and “nonsponsor” arms) (58 trials involving 15,026 patients from 101 citations identified).
Data Extraction: Data on dosing, efficacy, baseline severity, and adverse events were extracted by 2 of the authors.
Results: Meta-analyses were used to examine dosing and efficacy data. Using consensus guidelines for medication dosing, we determined that sponsor medication was dosed relatively higher than nonsponsor medication, in 37% (22/60) of comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed higher (χ22 = 25.9, P < .001). Trials in which sponsor drugs were dosed higher than nonsponsor drugs demonstrated higher remission rates for the sponsor drug (OR = 1.28, 95% CI = 1.11–1.47, P < .001). These results were confirmed using regulatory dosing guidelines. There was no significant correlation between dosing or outcome with baseline severity or adverse events.
Conclusions: Sponsor drugs are dosed higher than nonsponsor drugs in antidepressant randomized controlled trials, and higher dosing is associated with better sponsor drug outcomes in some cases.
J Clin Psychiatry 2012;73(2):e277–e287
© Copyright 2012 Physicians Postgraduate Press, Inc.
Submitted: June 7, 2011; accepted August 31, 2011 (doi:10.4088/JCP.11r07204).
Corresponding author: Mark Sinyor, MD, Sunnybrook Health Sciences Centre, Department of Psychiatry, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada (email@example.com).