Healthy Skepticism Library item: 12932

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Publication type: Journal Article

Kirsch I, Deacon BJ, Huedo-medina TB, Scoboria A, Moore TJ, Johnson BT.
Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration
PLoS 2008 Feb 26; 5:(2):
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045

Abstract:

Background
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placebo treatment, and when unpublished trial data are included, the benefit falls below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published and unpublished clinical trials.

Methods and Findings
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.

Conclusions
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.

Keywords:
Antidepressant, SSRI, meta-analysis, FDA