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dc.contributor.authorSchalkwijk, Stein
dc.contributor.authorUndurraga, Juan
dc.contributor.authorTondo, Leonardo
dc.contributor.authorBaldessarini, Ross J.
dc.date.accessioned2019-10-17T05:18:56Z
dc.date.issued2014
dc.identifier.citationSchalkwijk, Stein, Juan Undurraga, Leonardo Tondo, and Ross J. Baldessarini. 2014. “Declining Efficacy in Controlled Trials of Antidepressants: Effects of Placebo Dropout.” The International Journal of Neuropsychopharmacology 17 (8). Oxford University Press (OUP): 1343–52. doi:10.1017/s1461145714000224.
dc.identifier.issn1461-1457
dc.identifier.issn1469-5111
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41555757*
dc.description.abstractDrug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo- treatment. As these trends require adequate explanation, we tested the hypothesis that decreasing trial-dropout rates may be an important contributor. We gathered reports of peer-reviewed, placebo-controlled trials of antidepressants (1980-2011) by computerized literature searching, and applied meta-analysis, meta-regression and multiple linear regression methods to evaluate associations of dropout rates and other factors of interest, to reporting year and reported efficacy [standardized mean drug-placebo difference (SMD) as Hedges' g-statistic]. In 56 trials meeting inclusion and exclusion criteria, we confirmed significant overall efficacy of antidepressants but declining drug-placebo contrasts over the past three decades. Among other changes, there was a corresponding increase in placebo-associated improvement with a decline in placebo-dropout rate, mainly for lack of efficacy. These effects were found only when last-observation-carried-forward (LOCF) analyses were used. Other trial-design and subject factors, including drug-responses and drug-dropout rates, were much less associated with efficacy. We propose that declining placebo-dropout rates ascribed to inefficacy combined with use of LOCF analyses led to increasing improvement in placebo-arms that contributed to declining antidepressant-placebo contrasts in controlled treatment trials since the 1980s.
dc.language.isoen_US
dc.publisherOxford University Press
dash.licenseLAA
dc.titleDeclining efficacy in controlled trials of antidepressants: effects of placebo dropout
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
dash.depositing.authorTondo, Leonardo::8007a917adba0001d1d35804aefd89ca::600
dc.date.available2019-10-17T05:18:56Z
dash.workflow.comments1Science Serial ID 103564
dc.identifier.doi10.1017/S1461145714000224
dash.source.volume17;8
dash.source.page1343-1352


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