Benefits from antidepressants: synthesis of 6-week patient-level outcomes from
double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.
Author(s): Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ.
Affiliation(s): Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
rdg@uchicago.edu
Publication date & source: 2012, Arch Gen Psychiatry. , 69(6):572-9
CONTEXT: Some meta-analyses suggest that efficacy of antidepressants for major
depression is overstated and limited to severe depression.
OBJECTIVE: To determine the short-term efficacy of antidepressants for treating
major depressive disorder in youth, adult, and geriatric populations.
DATA SOURCES: Reanalysis of all intent-to-treat person-level longitudinal data
during the first 6 weeks of treatment of major depressive disorder from 12 adult,
4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride
and 21 adult trials of venlafaxine hydrochloride.
STUDY SELECTION: All sponsor-conducted randomized controlled trials of fluoxetine
and venlafaxine.
DATA EXTRACTION: Children's Depression Rating Scale-Revised scores (youth
population), Hamilton Depression Rating Scale scores (adult and geriatric
populations), and estimated response and remission rates at 6 weeks were analyzed
for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and
for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving
extended-release venlafaxine.
DATA SYNTHESIS: Patients in all age and drug groups had significantly greater
improvement relative to control patients receiving placebo. The differential rate
of improvement was largest for adults receiving fluoxetine (34.6% greater than
those receiving placebo). Youths had the largest treated vs control difference in
response rates (24.1%) and remission rates (30.1%), with adult differences
generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients
had the smallest drug-placebo differences, an 18.5% greater rate of improvement,
9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced
larger effects than extended-release venlafaxine. Baseline severity could not be
shown to affect symptom reduction.
CONCLUSIONS: To our knowledge, this is the first research synthesis in this area
to use complete longitudinal person-level data from a large set of published and
unpublished studies. The results do not support previous findings that
antidepressants show little benefit except for severe depression. The
antidepressants fluoxetine and venlafaxine are efficacious for major depressive
disorder in all age groups, although more so in youths and adults compared with
geriatric patients. Baseline severity was not significantly related to degree of
treatment advantage over placebo.
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