Research Summary: Antidepressant Response in Major Depressive Disorder: A Meta-Regression Comparison of Randomized Controlled Trials and Observational Studies



To compare response to antidepressants between randomized controlled trials
(RCTs) and observational trials.

Methods and Findings

Published and unpublished studies (from 1989 to 2009) were searched for by 2
reviewers on Medline, the Cochrane library, Embase,,
Current Controlled Trial, bibliographies and by mailing key organisations
and researchers. RCTs and observational studies on fluoxetine or venlafaxine
in first-line treatment for major depressive disorder reported in English,
French or Spanish language were included in the main analysis. Studies
including patients from a wider spectrum of depressive disorders (anxious
depression, minor depressive episode, dysthymia) were added in a second
analysis. The main outcome was the pre-/post-treatment difference on
depression scales standardised to 100 (17-item or 21-item Hamilton Rating
Scale for Depression or Montgomery and ├ůsberg Rating Scale) in each
study arm. A meta-regression was conducted to adjust the comparison between
observational studies and RCTs on treatment type, study characteristics and
average patient characteristics. 12 observational studies and 109 RCTs
involving 6757 and 11035 patients in 12 and 149 arms were included in the
main analysis. Meta-regression showed that the standardised treatment
response in RCTs is greater by a magnitude of 4.59 (2.61 to 6.56). Study
characteristics were related to standardised treatment response, positively
(study duration, number of follow-up assessments, outpatients versus
inpatients, per protocol analysis versus intention to treat analysis) or
negatively (blinded design, placebo design). At patient level, response
increased with baseline severity and decreased with age. Results of the
second analysis were consistent with this.


Response to antidepressants is greater in RCTs than in observational studies.
Observational studies should be considered as a necessary complement to


Publisher: Public Library of Science

Date Published: 8-June-2011

Author(s): Naudet F., Maria A., Falissard B.


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