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Antidepressants for Major Depressive Disorder and Dysthymic Disorder in Patients With Comorbid Alcohol Use Disorders: A Meta-Analysis of Placebo-Controlled Randomized Trials

Nadia Iovieno, MD; Enrico Tedeschini, MD; Kate H. Bentley, BA; A. Eden Evins, MD, MPH; and George I. Papakostas, MD

Published: April 19, 2011

Article Abstract

Objective: Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders.

Data Sources: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder.

Study Selection: 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive).

Results: We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or whether they were used in pure MDD or in combined MDD and dysthymic disorder populations.

Conclusions: These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed.

J Clin Psychiatry 2011;72(8):1144-1151

Submitted: May 4, 2010; accepted September 15, 2010.

Online ahead of print: April 19, 2011 (doi:10.4088/JCP.10m06217).

Corresponding author: Nadia Iovieno, MD, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 50 Staniford Street-Suite 401, Boston, MA 02114 (

Volume: 72

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