Little is known about study design
The authors of this study had access only to limited information about inclusion criteria and the composition of initial study populations or settings. There is a difference between a trial designed to evaluate the “efficacy” of an intervention (“the beneficial and harmful effects of an intervention under controlled circumstances”) and the “effectiveness” of an intervention (the “beneficial and harmful effects of the intervention under usual circumstances”).12 It is not clear which of the 117 studies were efficacy studies and which were effectiveness studies. This may limit the overall generalizability of the study results to a primary care population.
Studies included in this meta-analysis were selected exclusively from published literature. There is some evidence that there is a bias toward the publication of studies with positive results, which may have the effect of overstating the effectiveness of a given antidepressant.13 However, we have no reason to believe that this bias would favor any particular drug.
Most of the included studies were sponsored by drug companies. Notably, pharmaceutical companies have the option of continuing to conduct trials of medications until a study results in a positive finding for their medication, with no penalty for the suppression of equivocal or negative results (negative publication bias). Under current FDA guidelines, there is little transparency to the consumer as to how many trials have been undertaken and the direction of the results, published or unpublished.14
We doubt that either publication bias or the design and sponsorship of the studies included in this meta-analysis present significant threats to the validity of these findings over other sources upon which guidelines rely, given that these issues are common to much of the research on pharmacologic therapy. We also doubt that the compensation of the authors by pharmaceutical companies would bias the outcome of the study in this instance. One of the authors (TAF) received compensation from Pfizer, the maker of Zoloft, which is also available as generic sertraline. None of the authors received compensation from Forest Pharmaceuticals, the makers of Lexapro (escitalopram).
CHALLENGES TO IMPLEMENTATION: No major barriers are anticipated
Both sertraline and escitalopram are covered by most health insurers. As noted above, sertraline is available in generic formulation, and is therefore much less expensive than escitalopram. In a check of online drug prices, we found a prescription for a 3-month supply of Lexapro (10 mg) to cost about $250; a 3-month supply of generic sertraline (100 mg) from the same sources would cost approximately $35 (www.pharmcychecker.com). Both Pfizer, the maker of Zoloft, and Forest Pharmaceuticals, the maker of Lexapro, have patient assistance programs to make these medications available to low-income, uninsured patients.
Acknowledgements
The PURLs Surveillance System is supported in part by Grant Number UL1RR02499 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
The authors wish to acknowledge Sofia Medvedev, PhD, of the University HealthSystem Consortium in Oak Brook, Ill, for analysis of the National Ambulatory Medical Care Survey data and the UHC Clinical Database.
