Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration

Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initia...

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Veröffentlicht in:PLoS medicine 2008-02, Vol.5 (2), p.e45
Hauptverfasser: Kirsch, Irving, Deacon, Brett J, Huedo-Medina, Tania B, Scoboria, Alan, Moore, Thomas J, Johnson, Blair T
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container_start_page e45
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creator Kirsch, Irving
Deacon, Brett J
Huedo-Medina, Tania B
Scoboria, Alan
Moore, Thomas J
Johnson, Blair T
description Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug-placebo difference scores. Drug-placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.
doi_str_mv 10.1371/journal.pmed.0050045
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subjects Antidepressants
Antidepressive Agents - therapeutic use
Clinical trials
Clinical Trials as Topic - standards
Databases, Factual - standards
Depressive Disorder - drug therapy
Depressive Disorder - epidemiology
Depressive Disorder - psychology
Drugs and Adverse Drug Reactions
Evidence-Based Healthcare
Food
Humans
Licenses
Mental Health
Meta-analysis
Mood Disorders (Including Depression)
Severity of Illness Index
Statistical analysis
Statistical methods
Studies
Systematic Reviews and Meta-Analyses
United States - epidemiology
United States Food and Drug Administration - standards
title Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration
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