Treating depression and anxiety with the benzodiazepine alprazolam: new Cochrane review recommends caution


Antidepressants and psychotherapies are the mainstay for treating depression, but another option is the benzodiazepine drug alprazolam, which is recommended for treating depression when anxiety is also involved.

Some doctors prescribe a short course of benzodiazepines to help depressed and anxious patients, but this is not supported by NICE guidance. High-potency tranquillisers like alprazolam are thought to have side-effects including dependence, rebound anxiety, memory impairment, accident-proneness and discontinuation syndrome.

A new systematic review from the Cochrane Depression, Anxiety and Neurosis Group suggests that alprazolam may be as effective as antidepressants in treating depression, but the authors urge caution because of the quality of the studies included in their review.

They conducted the usual systematic Cochrane search looking for randomised controlled trials (RCTs) of alprazolam versus placebo or conventional antidepressants for depression in adults, excluding studies with inpatients only. Their search included all RCTs published up until February 2012 and they did not apply any language restrictions.

They found 21 RCTs including a total of 2,693 patients. Typical study duration was 4-6 weeks and 6 of the included studies had a high risk of bias.

Two authors from their team carried out independent data extraction and assessed the quality of the included research, to ensure that their interpretation of the evidence was accurate.

They measured two main outcomes:

  1. The mean difference (MD) in reduction of depression on a continuous measure of depression symptoms
  2. The risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CI)

Here’s what they found:

  • Alprazolam reduced depression symptoms better than placebo
    • (MD -5.34, 95% CI -7.48 to -3.20; I2 = 68%)
    • (Risk difference RD 0.32, 95% CI 0.22 to 0.42; I2 = 0%)
  • Alprazolam reduced depression symptoms as well as tricyclic antidepressants
    • (MD 0.25, 95% CI -0.93 to 1.43; I2 = 55%)
    • (RR 0.86, 95% CI 0.75 to 0.99; I2 = 37%)
    • (RD -0.11, 95% CI -0.24 to 0.01; I2 = 58%)
    • (Number needed to treat to benefit NNTB 9, 95% CI 4 to 100)

But the included studies had a number of weaknesses:

The reviewers concluded:

The best evidence currently available suggests that alprazolam may be moderately more effective than a placebo, and as effective as conventional antidepressants, in the treatment of major depression.

However, the multiple shortcomings of the currently available evidence limit confidence in these findings.


van Marwijk H, Allick G, Wegman F, Bax A, Riphagen II. Alprazolam for depression. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD007139. DOI: 10.1002/14651858.CD007139.pub2.

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