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Does Randomized Evidence Support Sertraline as First-Line Antidepressant for Adults With Acute Major Depression? A Systematic Review and Meta-Analysis

Andrea Cipriani, M.D.; Toshiaki A. Furukawa, M.D., Ph.D.; John R. Geddes, M.D.; Lara Malvini, M.D.; Alessandra Signoretti, M.D.; Hugh McGuire, M.A.; Rachel Churchill, M.Sc., Ph.D.; Atsuo Nakagawa, M.D.; and Corrado Barbui, M.D.; on behalf of the MANGA Study Group

Objective: Preliminary evidence suggested that sertraline might be slightly superior to other antidepressant medications in terms of efficacy. The aim of this study was to carry out a systematic review and meta-analysis to compare sertraline with any other antidepressant in the acute phase treatment of major depression at 8 weeks.

Data Sources: MEDLINE; EMBASE; the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register; and the Cochrane Central Register of Controlled Trials up to August 2007. No language restriction. The following search strategy was used: diagnosis =depress* or dysthymi* or adjustment disorder* or mood disorder* or affective disorder or affective symptoms, and intervention (or free text) =sertraline. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.

Study Selection: Only randomized controlled trials allocating patients with major depression to sertraline versus any other antidepressant agent.

Data Extraction: Three reviewers independently extracted data. A double-entry procedure was employed by 2 reviewers. To analyze data, a very conservative approach with a 99% confidence interval (CI) and a random effects model was used. Information extracted included study characteristics, participant characteristics, intervention details, and outcome measures, such as the number of patients who responded to treatment and the number of patients who failed to complete the study by any cause at 8 weeks.

Data Synthesis: This systematic review and meta-analysis found that sertraline is statistically significantly better than fluoxetine (relative risk [RR] = 0.85, 99% CI = 0.74 to 0.98; number needed to treat [NNT] = 12) and other SSRIs as a class (RR = 0.88, 99% CI = 0.78 to 0.99; NNT = 17) and highlighted a consistent even though not statistically significant trend in favor of sertraline over many other antidepressants both in terms of efficacy and acceptability in a homogeneous and clinically relevant time frame of 8 weeks.

Conclusions: The results of this review suggest that sertraline may be a candidate as the initial choice of antidepressant for people with major depression.

(J Clin Psychiatry 2008;69:1732-1742. Online Ahead of Print November 4, 2008.)

Received Jan. 8, 2008; accepted Feb. 28, 2008. From the Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy (Drs. Cipriani, Malvini, Signoretti, and Barbui); the Department of Psychiatry, Nagoya City University Medical School, Nagoya, Japan (Dr. Furukawa); the Department of Psychiatry, University of Oxford, Oxford, United Kingdom (Dr. Geddes); Cochrane Collaboration Depression, Anxiety, and Neurosis Review Group, Health Services Research Department, King's College Institute of Psychiatry, London, United Kingdom (Dr. Churchill and Mr. McGuire); and the Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan (Dr. Nakagawa).

This study received no funding from drug companies. The authors are grateful to the Fondazione Cariverona, Verona, Italy, for providing a 3-year grant to the World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Organization at the University of Verona, directed by Professor Michele Tansella, M.D. Dr. Tansella has no pertinent financial affiliations or other relationships to report relevant to the subject of this article.

MANGA Study group: the Meta-Analyses of New Generation Antidepressants (MANGA) project is a research project in which a group of researchers agreed to systematically review all available evidence for specific newer antidepressants, in order to inform clinical practice and mental health policies.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: Andrea Cipriani, M.D., Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Policlinico "G.B. Rossi" Piazzale L.A. Scuro, 10, 37134 Verona, Italy (e-mail: andrea.cipriani@univr.it).
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