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Alprazolam for depression

  • Review
  • Intervention




The 'off-label' effect of alprazolam on depression has not been systematically evaluated.


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; I2 = 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; I2 = 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; I2 = 55%). However, for dichotomised depression severity, alprazolam had less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; I2 = 37%; RD -0.11, 95% CI -0.24 to 0.01; I2 = 58%; NNTB 9, 95% CI 4 to 100). The RD of all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; I2 = 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.








Cochrane Central Register of Controlled Trials、およびコクラン・ライブラリ(全年~2012年2月)、EMBASE(1970~2012年2月)、MEDLINE(1950~2012年2月)、PsycINFO(1960~2012年2月)の各文献データベースに登録された関連性のあるランダム化比較試験(RCT)を含むCochrane Depression, Anxiety and Neurosis Group Registerを検索した。 2名のレビューアが可能性のあるすべての研究の抄録を評価して、関連性のある試験を同定した。言語の制限は設けなかった。







症状の改善についてアルプラゾラムをプラセボと比べた場合、すべての推定値はアルプラゾラムの有効性を示した。有効性データの統合推定値は、試験終了時で中等度の平均差(MD)が認められた(-5.34、95%CI -7.48~-3.20;I2 = 68%)。 臨床反応(50%の改善)についての二値指標のリスク差(RD)は0.32で、アルプラゾラムが好ましく(95%CI 0.22~0.42;I2 = 0%)、治療必要数(NNTB)は3(95%CI 2~5)であった。 すべての理由による投与中止についてのRDはアルプラゾラムとプラセボで差を認めなかった。

うつ病重症度を連続的指標で測定した場合、アルプラゾラムの効果はあらゆる既存の抗うつ薬をあわせた効果と、統計学的かつ臨床的に変わらなかった(MD 0.25、95% CI -0.93~1.43;I2 = 55%)。 しかし、うつ病重症度を二値指標でみた場合には、抗うつ薬に比べてアルプラゾラムの方が効果が少なかった(RR 0.86、95%CI 0.75~0.99;I2 = 37%;RD -0.11、95%CI -0.24~0.01;I2 = 58%;治療必要数 9、95% CI 4~100)。 すべての理由による投与中止についてのRDは-0.04(95% CI -0.07~0.00;I2 = 35%)でアルプラゾラムが好ましい結果であった。




《実施組織》三浦 智史監訳 厚生労働省委託事業によりMindsが実施した。[2012.11.14]
《注意》 この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、コクラン日本支部までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review、Updated reviewとも日単位で更新されています。最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Alprazolam for depression

Additional options to help those with depression control their mood, besides psychotherapy and antidepressants, can be important, especially when there is also anxiety involved. One of the drug options is alprazolam, a benzodiazepine. We evaluated the effect of alprazolam for depression. 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. We cannot conclude whether this is due to its specific antidepressant effect or to a non-specific effect on sleep and anxiety. There were relatively few short-term side effects. However, the multiple shortcomings of the currently available evidence, including probable sponsorship bias, publication bias, the age of the studies and the heterogeneity of the results, limit confidence in these findings.





《実施組織》三浦 智史監訳 厚生労働省委託事業によりMindsが実施した。[2012.11.14]
《注意》 この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、コクラン日本支部までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review、Updated reviewとも日単位で更新されています。最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Laički sažetak

Alprazolam za depresiju

Dodatne mogućnosti koje pomažu osobama s depresijom kontrolirati raspoloženje, uz psihoterapiju i antidepresive, mogu biti važne, posebice kada je uključena i anksioznost. Jedna od terapijskih mogućnosti je benzodiazepin alprazolam. U ovom Cochrane sustavnom pregledu procijenjen je učinak alprazolama za depresiju. Najbolji trenutno dostupni dokazi upućuju da bi alprazolam mogao biti umjereno učinkovitiji od placeba te jednako učinkovit kao uobičajeni antidepresivi u terapiji velikog depresivnog poremećaja. Nije bilo moguće utvrditi je li to zbog specifičnog antidepresivnog učinka ili nespecifičnog učinka na san i anksioznost. Zabilježeno je relativno malo kratkoročnih nuspojava. Međutim, višestruki nedostatci trenutno dostupnih dokaza, uključujući moguću pristranost zbog financiranja od strane sponzora, pristranost pri objavljivanju, starost studija i različitost rezultata, ograničavaju povjerenje u te zaključke.

Bilješke prijevoda

Hrvatski Cochrane
Preveo: Adam Galkovski
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: