A Patient-Level Meta-analysis

ANTIDEPRESSANT MEDICATION (ADM) represents the current standard of treatment for major depressive disorder (MDD). Antidepressant medication has been shown to be superior to placebo in thousands of controlled clinical trials over the past 5 decades. The extent to which ADM outperforms placebo (which controls for nonpharmacological aspects of ADM) can be used to index the “true” pharmacological effect of ADM in clinical settings. The randomized, double-blind, placebo-controlled trial is the gold standard for testing treatment efficacy and affords the opportunity to identify patient characteristics that predict differential pharmacological response. Baseline symptom severity is one dimension that may affect treatment outcome. Kirsch et al and Khan et al presented independent meta-analyses of randomized placebo-controlled trials based on data from the Food and Drug Administration (FDA) clinical trial database. Using mean scores and standard deviations on the Hamilton Depression Rating Scale (HDRS) from each study, they examined the effect of baseline symptom severity on the relative efficacy of ADM vs placebo. Kirsch et al found that as the mean baseline HDRS score increased, the magnitude of HDRS change decreased for placebo but remained unchanged for ADM. Khan et al did not find a significant relationship between baseline scores and symptom change for the Author Affiliations: Departments of Psychology (Mr Fournier and Dr DeRubeis) and Psychiatry (Dr Amsterdam), University of Pennsylvania, Philadelphia; Departments of Psychology (Dr Hollon) and Psychiatry (Dr Shelton), Vanderbilt University, Nashville, Tennessee; Department of Psychology, University of Colorado at Boulder (Dr Dimidjian); and Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque (Dr Fawcett). Corresponding Author: Jay C. Fournier, MA, Department of Psychology, University of Pennsylvania, 3720 Walnut St, Philadelphia, PA 19104 (jcf@sas.upenn .edu). Context Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression.