Comparative Benefits and Harms of Second-Generation Antidepressants: Background Paper for the American College of Physicians

18 November 2008 | Volume 149 Issue 10 | Pages 734-750

Background: Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing.

Purpose: To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults.

Data Sources: MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research.

Study Selection: Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included.

Data Extraction: Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes.

Data Synthesis: If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression.

Limitation: Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy.

Conclusion: Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.

Author and Article Information

From Danube University, Krems, Austria; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, and Regenstrief Institute, Indianapolis, Indiana; University of Pittsburgh, Pittsburgh, Pennsylvania; and RTI International, Research Triangle Park, North Carolina.

Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

Acknowledgment: The authors thank Timothy S. Carey, MD, MPH, and Stacey Williams, MA, from the University of North Carolina at Chapel Hill, and also Linda Lux, MPA, and Loraine Monroe of RTI International.

Grant Support: By a contract from the Agency for Healthcare Research and Quality to the RTI International–University of North Carolina Evidence-based Practice Center (contract no. 290-02-0016).

Potential Financial Conflicts of Interest: Employment: A. DeVeaugh-Geiss (GlaxoSmithKline). Consultancies: B.N. Gaynes (Pfizer, Wyeth-Ayerst, Shire Pharmaceutical). Honoraria: B.N. Gaynes (GlaxoSmithKline). Stock ownership or options (other than mutual funds): A. DeVeaugh-Geiss (GlaxoSmithKline). Expert testimony: B.N. Gaynes (Phillips Lytle). Grants received: B.N. Gaynes (Agency for Healthcare Research and Quality, National Institute of Mental Health, Bristol-Myers Squibb, Novartis, Pfizer, Robert Wood Johnson Foundation, M-3 Corporation), R.A. Hansen (GlaxoSmithKline). Grants pending: B.N. Gaynes (National Institute of Mental Health, Agency for Healthcare Research and Quality).

Requests for Single Reprints: Gerald Gartlehner, MD, MPH, Danube University, Karl Dorrek-Straße, 3500 Krems, Austria; e-mail, gerald.gartlehner{at}donau-uni.ac.at.

Current Author Addresses: Dr. Gartlehner: Danube University, Karl Dorrek-Straße, 3500 Krems, Austria.

Dr. Gaynes: Department of Psychiatry, Campus Box 7160, University of North Carolina, Chapel Hill, NC 27599.

Dr. Hansen: University of North Carolina, School of Pharmacy, Campus Box 7360, Chapel Hill, NC 27599.

Ms. Thieda and Ms. Morgan: University of North Carolina, Sheps Center for Health Services Research, 725 Martin Luther King Jr. Boulevard, Chapel Hill, NC 27599.

Ms. DeVeaugh-Geiss: University of North Carolina, Department of Epidemiology, Campus Box 7435, Chapel Hill, NC 27599.

Dr. Krebs: Roudebush Veterans Affairs Medical Center, 1481 West 10th Street, Indianapolis, IN 46202.

Dr. Moore: Center for Research on Health Care Data, University of Pittsburgh, 200 Meyran Avenue, Suite 300, Pittsburgh, PA 15213.

Dr. Lohr: RTI International, PO Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194.

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Comparative Benefits and Harms of Second-Generation Antidepressants

Thomas E. Finucane

Annals Online, 5 Dec 2008 [Full text]