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Neuropsychopharmacology. 2012 Mar;37(4):851-64. doi: 10.1038/npp.2011.306. Epub 2011 Dec 14.

Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review.

Author information

  • 1Department of Psychiatry, Harvard Medical School, Psychopharmacology Program and International Consortium for Psychotic and Mood Disorders Research, Mailman Research Center, McLean Division of Massachusetts General Hospital, Boston, MA, USA.

Abstract

Antidepressant-placebo response-differences (RDs) in controlled trials have been declining, potentially confounding comparisons among older and newer drugs. For clinically employed antidepressants, we carried out a meta-analytic review of placebo-controlled trials in acute, unipolar, major depressive episodes reported over the past three decades to compare efficacy (drug-placebo RDs) of individual antidepressants and classes, and to consider factors associated with year-of-reporting by bivariate and multivariate regression modeling. Observed drug-placebo differences were moderate and generally similar among specific drugs, but larger among older antidepressants, notably tricyclics, than most newer agents. This outcome parallels selective increases in placebo-associated responses as trial-size has increased in recent years. Study findings generally support moderate efficacy of clinically employed antidepressants for acute major depression, but underscore limitations of meta-analyses of controlled trials for ranking drugs by efficacy. We suggest that efficiency and drug-placebo differences may be improved with fewer sites and subjects, and better quality-control of diagnostic and clinical assessments.

PMID:
22169941
[PubMed - indexed for MEDLINE]
PMCID:
PMC3280655
Free PMC Article

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