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Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1199 (Published 11 March 2011) Cite this as: BMJ 2011;342:d1199

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Fluoxetine top of the ranking for GAD: garbage in, garbage out?

The results of this Multiple-Treatments Meta-analysis (MTM), which
appraised the evidence for comparative efficacy and tolerability of drug
treatments and placebo in patients with generalised anxiety disorders,
suggest that fluoxetine has the highest probability to be the best
treatment in terms of response and remission. As reported in the
accompanying editorial, this conclusion is based on 33 patients who
received fluoxetine in one three-arm study comparing fluoxetine with
venlafaxine and placebo. More precisely, the data were taken from a post-
hoc subgroup analysis of a study that was prospectively designed to
demonstrate the efficacy of venlafaxine in outpatients with depression and
anxiety. Following completion of the study, a subset of patients who had a
recorded formal DSM-IV diagnosis of generalized anxiety disorder was
identified in the dataset and analyzed. The implications of this design
include that patients in this subgroup analysis had a diagnosis of major
depressive disorder in addition to that of generalized anxiety disorder.
Moreover, random allocation was not stratified by comorbid diagnosis of
generalized anxiety disorder, and the groups were not similar at baseline
in terms of socio-demographic and clinical characteristics.

Clearly, we are all well aware of the problems associated with
subgroup analyses in clinical trials, but what strikes here is that the
results of this subgroup analysis were not in favour of fluoxetine over
venlafaxine: the adjusted mean difference from placebo (HAM-A total score)
was 2.5 (with a 95% confidence interval (95% CI) between -1.7 and 6.7) for
fluoxetine and 4.5 (95% CI 0.2 to 8.7) for venlafaxine. In terms of
responders, 59% responded to venlafaxine and 45% to fluoxetine. Remission
rate was 12/33 (36%) for fluoxetine and 10/32 (31%) for venlafaxine.

In addition to raising concerns on the inclusion of the fluoxetine
study, we wonder how the MTM methodology has been able to rank fluoxetine
as first treatment on the basis of this direct evidence. We had experience
of using the MTM approach in the field of antidepressants for major
depression and we found that combining direct and indirect evidence
increased precision without materially conflicting results, which does not
seem the case in the present analysis.

Competing interests: No competing interests

16 March 2011
Corrado Barbui
Psychiatrist
Andrea Cipriani
University of Verona