Alprazolam for depression.
Author(s): van Marwijk H, Allick G, Wegman F, Bax A, Riphagen II.
Affiliation(s): Department of General Practice, EMGO Institute for Health and Care Research, VU
University Medical Center, Amsterdam, Netherlands. hwj.vanmarwijk@vumc.nl
Publication date & source: 2012, Cochrane Database Syst Rev. , 7:CD007139
BACKGROUND: The 'off-label' effect of alprazolam on depression has not been
systematically evaluated.
OBJECTIVES: To determine the antidepressant effect, including tolerability and
acceptability, of alprazolam as monotherapy for major depression, when compared
to placebo and conventional antidepressants in outpatients and patients in
primary care.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
and the Cochrane Depression, Anxiety and Neurosis Group Register, which includes
relevant randomised controlled trials from the following bibliographic databases:
The Cochrane Library (all years to February 2012); EMBASE (1970 to February
2012); MEDLINE (1950 to February 2012) and PsycINFO (1960 to February 2012). Two
review authors identified relevant trials by assessing the abstracts of all
possible studies. We applied no language restrictions.
SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of alprazolam
versus placebo or conventional antidepressants for depression in adults,
excluding studies with inpatients only.
DATA COLLECTION AND ANALYSIS: Two review authors performed the data extraction
and 'Risk of bias' assessment independently with disagreements resolved through
discussion with a third review author. Primary outcomes included the mean
difference (MD) in reduction of depression on a continuous measure of depression
symptoms, and the risk ratio (RR) of the clinical response based on a dichotomous
measure, with 95% confidence intervals (CI).
MAIN RESULTS: We identified 21 alprazolam studies (22 reports) with a total of
2693 participants. Seven studies used a placebo (n = 771) and 20 used cyclic
antidepressants (n = 1765). The typical duration of the studies was four to six
weeks. We considered six studies to have a high risk of bias.When alprazolam was
compared with placebo for reduction in symptoms all estimates indicated a
positive effect for alprazolam. Pooled estimates of efficacy data showed a
moderately large continuous mean difference (MD) at the end of trial (-5.34, 95%
CI -7.48 to -3.20; I(2) = 68%). The risk difference (RD) for the dichotomous
measure of clinical response (50% improvement) was 0.32 in favour of alprazolam
(95% CI 0.22 to 0.42; I(2) = 0%), with a number needed to treat to benefit (NNTB)
of 3 (95% CI 2 to 5). The RD of all-cause withdrawals did not differ between
alprazolam and placebo.When depression severity was measured as a continuum the
effect of alprazolam did not differ statistically or clinically from the effects
of any of the conventional antidepressants combined (MD 0.25, 95% CI -0.93 to
1.43; I(2) = 55%). However, for dichotomised depression severity, alprazolam had
less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; I(2) = 37%; RD
-0.11, 95% CI -0.24 to 0.01; I(2) = 58%; NNTB 9, 95% CI 4 to 100). The RD of
all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; I(2) = 35%), in favour of
alprazolam.
AUTHORS' CONCLUSIONS: Alprazolam appears to reduce depressive symptoms more
effectively than placebo and as effectively as tricyclic antidepressants.
However, the studies included in the review were heterogeneous, of poor quality
and only addressed short-term effects, thus limiting our confidence in the
findings. Whilst the rate of all-cause withdrawals did not appear to differ
between alprazolam and placebo, and withdrawals were less frequent in the
alprazolam group than in any of the conventional antidepressants combined group,
these findings should be interpreted with caution, given the dependency
properties of benzodiazepines.
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