Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration
Kirsch I, Deacon BJ, Huedo-Medina TB,
Scoboria A, Moore TJ, Johnson BT.
Department of Psychology, University of Hull,
Hull, United Kingdom.
PLoS Med. 2008 Feb;5(2):e45.


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Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance.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is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials.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.
Big Pharma
'Publication bias'
Ghost authorship
Medical ghostwriting
The David Healy Affair
He who pays the piper...?
Ghostwriting in medical publications
Ghostwriting in peer-reviewed medical journals
The role of pharmaceutical company gifts to doctors
Medical writers in the pay of pharmaceutical companies
Ghost marketing and ghostwriting in peer-reviewed medical journals
Ghost authorship, gift authorship, non-disclosure and conflicts of interest
Are commonly prescribed "new generation" antidepressants little better than placebos?
Selective publication of clinical trials leads to unrealistic estimates of antidepressant efficacy

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