Alprazolam for depression

Evidence Summaries

Level of Evidence = C
Alprazolam may reduce depressive symptoms more effectively than placebo and as effectively as tricyclic antidepressants.

A Cochrane review 1 included 21 studies with a total of 2693 subjects with depression. Seven studies used placebo (n = 771) and 20 used cyclic antidepressants (n = 1765). The typical duration of the studies was 4 to 6 weeks. 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; 7 studies, n=771). 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; 3 studies, n=312), with NNT 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; 17 studies, n=1636). However, for dichotomised depression severity, alprazolam had less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; RD -0.11, 95% CI -0.24 to 0.01; NNT 9, 95% CI 4 to 100; 7 studies, n=543). The RD of all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; 18 studies, n=1873), in favour of alprazolam.

Comment: The quality of the evidence is downgraded by study quality (unclear allocation concealment) and potential publication bias (all studies sponsored by the pharmaceutical company manufacturing alprazolam).


1. van Marwijk H, Allick G, Wegman F et al. Alprazolam for depression. Cochrane Database Syst Rev 2012;7:CD007139.  [PMID:22786504]

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