title: Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review.
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.
authors.affiliation: Department 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Undurraga
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000208:Acute Disease; D000928:Antidepressive Agents / Q000145:classification / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000639:trends*
chemical_list: D000928:Antidepressive Agents