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Meta-Analysis
. 2012 Jul 11;2012(7):CD007139.
doi: 10.1002/14651858.CD007139.pub2.

Alprazolam for depression

Harm van Marwijk  1 , Gideon Allick, Froukje Wegman, Arjan Bax, Ingrid I Riphagen
Affiliations
Meta-Analysis

Alprazolam for depression

Harm van Marwijk et al. Cochrane Database Syst Rev. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Harm van Marwijk has not received any payments from relevant stakeholders, such as pharmaceutical industries, for this project. He is involved with research in mental health in primary care. The majority of his projects are sponsored by the Dutch government. He is a member of a Dutch working party on revision of national guidelines for anxiety and depression. GA, FW, AB and IR: none declared.

Figures

1
1
2
2
1.1
1.1. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 1 Hamilton Depression Rating Scale (HDRS) continuous.
1.2
1.2. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 2 50% improvement versus less than 50% improvement RR.
1.3
1.3. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 3 50% improvement versus less than 50% improvement RD.
1.4
1.4. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 4 All‐cause withdrawals versus no withdrawals RR.
1.5
1.5. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 5 All‐cause withdrawals versus no withdrawals RD.
1.6
1.6. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 6 Withdrawal due to adverse effects versus no withdrawals RR.
1.7
1.7. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 7 Withdrawal due to adverse effects versus no withdrawals RD.
1.8
1.8. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 8 Withdrawal due to ineffectiveness versus no withdrawals RR.
1.9
1.9. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 9 Withdrawal due to ineffectiveness versus no withdrawals RD.
1.10
1.10. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 10 Hamilton Depression Rating Scale (HDRS) timeline week 1.
1.11
1.11. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 11 Hamilton Depression Rating Scale (HDRS) timeline week 2.
1.12
1.12. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 12 Hamilton Depression Rating Scale (HDRS) timeline week 3.
1.13
1.13. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 13 Hamilton Depression Rating Scale (HDRS) timeline week 4.
1.14
1.14. Analysis
Comparison 1 Alprazolam versus placebo, Outcome 14 Hamilton Depression Rating Scale (HDRS) timeline week 6.
2.1
2.1. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 1 HDRS continuous.
2.2
2.2. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 2 HDRS continuous (subgrouped by TCA comparator).
2.3
2.3. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 3 50% improvement vs less than 50% improvement RR.
2.4
2.4. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 4 50% improvement vs less than 50% improvement RR (subgrouped by TCA comparator).
2.5
2.5. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 5 50% improvement vs less than 50% improvement RD.
2.6
2.6. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 6 50% improvement vs less than 50% improvement RD (subgrouped by TCA comparator).
2.7
2.7. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 7 All‐cause withdrawals vs no withdrawals RR.
2.8
2.8. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 8 All‐cause withdrawals vs no withdrawals RR (subgrouped by TCA comparator).
2.9
2.9. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 9 All‐cause withdrawals vs no withdrawals RD.
2.10
2.10. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 10 All‐cause withdrawals vs no withdrawals RD (subgrouped by TCA comparator).
2.11
2.11. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 11 Adverse effects withdrawals vs no withdrawals RR.
2.12
2.12. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 12 Adverse effects withdrawals vs no withdrawals RR (subgrouped by TCA comparator).
2.13
2.13. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 13 Adverse effects withdrawals vs no withdrawals RD.
2.14
2.14. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 14 Adverse effects withdrawals vs no withdrawals RD (subgrouped by TCA comparator).
2.15
2.15. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 15 Ineffectiveness withdrawals vs no withdrawals RR.
2.16
2.16. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 16 Ineffectiveness withdrawals vs no withdrawals RR (subgrouped by TCA comparator).
2.17
2.17. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 17 Ineffectiveness withdrawals vs no withdrawals RD.
2.18
2.18. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 18 Ineffectiveness withdrawals vs no withdrawals RD (subgrouped by TCA comparator).
2.19
2.19. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 19 HDRS timeline week 1.
2.20
2.20. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 20 HDRS timeline week 1 (subgrouped by TCA comparator).
2.21
2.21. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 21 HDRS timeline week 2.
2.22
2.22. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 22 HDRS timeline week 2 (subgrouped by TCA comparator).
2.23
2.23. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 23 HDRS timeline week 3.
2.24
2.24. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 24 HDRS timeline week 3 (subgrouped by TCA comparator).
2.25
2.25. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 25 HDRS timeline week 4.
2.26
2.26. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 26 HDRS timeline week 4 (subgrouped by TCA comparator).
2.27
2.27. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 27 HDRS timeline week 5.
2.28
2.28. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 28 HDRS timeline week 5 (subgrouped by TCA comparator).
2.29
2.29. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 29 HDRS timeline week 6.
2.30
2.30. Analysis
Comparison 2 Alprazolam versus TCAs, Outcome 30 HDRS timeline week 6 (subgrouped by TCA comparator).
3.1
3.1. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 1 Hamilton Depression Rating Scale (HDRS) continuous.
3.2
3.2. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 2 All‐cause withdrawals versus no withdrawals RR.
3.3
3.3. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 3 All‐cause withdrawals versus no withdrawals RD.
3.4
3.4. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 4 Adverse effects withdrawals versus no withdrawals RR.
3.5
3.5. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 5 Adverse effects withdrawals versus no withdrawals RD.
3.6
3.6. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 6 Ineffectiveness withdrawals versus no withdrawals RR.
3.7
3.7. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 7 Ineffectiveness withdrawals versus no withdrawals RD.
3.8
3.8. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 8 Hamilton Depression Rating Scale (HDRS) timeline week 2.
3.9
3.9. Analysis
Comparison 3 Alprazolam versus heterocyclics, Outcome 9 Hamilton Depression Rating Scale (HDRS) timeline week 4.
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