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Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression
Comparative Effectiveness Reviews, No. 46
Investigators: Gerald Gartlehner, MD, MPH, Richard A Hansen, PhD, Laura C Morgan, MA, Kylie Thaler, MD, MPH, Linda J Lux, MPA, Megan Van Noord, MSIS, Ursula Mager, PhD, MPH, Bradley N Gaynes, MD, MPH, Patricia Thieda, MA, Michaela Strobelberger, MA, Stacey Lloyd, MPH, Ursula Reichenpfader, MD, MPH, and Kathleen N Lohr, PhD.
Author Information and AffiliationsStructured Abstract
Background:
Depressive disorders such as major depressive disorder (MDD), dysthymia, and subsyndromal depression may be serious disabling illnesses. MDD affects more than 16 percent of adults at some point during their lifetimes. Second-generation antidepressants dominate the medical management of depressive disorders. These drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other drugs with related mechanisms of action that selectively target neurotransmitters.
Objectives:
The objective of this report was to compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive disorders, including variations of effects in patients with accompanying symptoms and patient subgroups.
Data Sources:
We updated a comparative effectiveness review published in 2007 by the Agency for Healthcare Research and Quality searching PubMed, Embase, The Cochrane Library, and International Pharmaceutical Abstracts up to January 2011.
Review Methods:
Two people independently reviewed the literature, abstracted data, and rated the risk of bias. If data were sufficient, we conducted meta-analyses of head-to-head trials of the relative benefit of response to treatment. In addition, we conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants.
Results:
From a total of 3,722 citations, we identified 248 studies of good or fair quality. Overall, no substantial differences in efficacy could be detected among second-generation antidepressants for the treatment of acute-phase MDD. Statistically significant differences in response rates between some drugs are small and likely not clinically relevant. No differences in efficacy were apparent in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbidities, although evidence within these subpopulations was limited.
Differences exist in the incidence of specific adverse events and the onset of action. Venlafaxine leads to higher rates of nausea and vomiting, sertraline to higher rates of diarrhea, and mirtazapine to higher rates of weight gain than comparator drugs. Bupropion causes lower rates of sexual dysfunction than other antidepressants. The evidence is insufficient to draw conclusions about the comparative efficacy and effectiveness for the treatment of dysthymia and subsyndromal depression.
Conclusions:
Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy and effectiveness. Differences with respect to onset of action and adverse events may be taken into consideration for the choice of a medication.
Contents
- Preface
- Acknowledgments
- Technical Expert Panel
- Peer Reviewers
- Executive Summary
- Introduction
- Methods
- Results
- Overview of all Key Questions
- Key Question 1a Efficacy or Effectiveness in Treating Depressive Disorders and Symptoms
- Key Question 1b Response to Antidepressant Agents After Successful Response in the Past
- Key Question 1c Differences in Efficacy and Effectiveness between Immediate- and Extended-Release Formulations
- Key Question 2 Efficacy or Effectiveness for Maintaining Remission or for Treating Patients With Unresponsive or Recurrent Disease
- Key Question 3 Efficacy or Effectiveness for Treating Symptoms Accompanying Depression
- Key Question 4 Safety, Adverse Events, Adherence
- Key Question 4a Comparative Harms and Adherence for Second-Generation Antidepressants
- Key Question 4b Comparative Harms, Adherence, and Persistence for Immediate- and Extended-Release Second-Generation Antidepressants
- Key Question 5 Efficacy, Effectiveness, and Harms for Selected Populations
- Discussion
- References
- Appendixes
- Appendix A Search Strategy
- Appendix B Excluded Studies
- Appendix C Evidence Tables
- Appendix D Poor-Quality Studies
- Appendix E Studies Included in Mixed-Treatment Comparisons and Meta-analyses
- Appendix F Bibliography of References by Database Searched
- Appendix G Strength of Evidence Tables
- Appendix H Review and Abstraction Forms
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10056-I. Prepared by: RTI–UNC Evidence-based Practice Center, Research Triangle Park, NC
Suggested citation:
Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux LJ, Van Noord M, Mager U, Gaynes BN, Thieda P, Strobelberger M, Lloyd S, Reichenpfader U, Lohr KN. Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An Update of the 2007 Comparative Effectiveness Review. (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center, Contract No. 290-2007-10056-I.) AHRQ Publication No. 12-EHC012-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2011. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
This report is based on research conducted by the RTI–UNC Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10056-I). The findings and conclusions in this document are those of the author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products or actions may not be stated or implied.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
- 1
540 Gaither Road, Rockville, MD 20850; www
.ahrq.gov
- Review Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians.[Ann Intern Med. 2008]Review Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians.Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, Morgan L, Lohr KN. Ann Intern Med. 2008 Nov 18; 149(10):734-50.
- Review Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults[ 2019]Review Adverse Effects of Pharmacologic Treatments of Major Depression in Older AdultsSobieraj DM, Baker WL, Martinez BK, Hernandez AV, Coleman CI, Ross JS, Berg KM, Steffens DC. 2019 Mar
- Review Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.[Ann Intern Med. 2011]Review Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux L, Van Noord M, Mager U, Thieda P, Gaynes BN, Wilkins T, et al. Ann Intern Med. 2011 Dec 6; 155(11):772-85.
- Review Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review.[Depress Anxiety. 2012]Review Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review.Thaler KJ, Morgan LC, Van Noord M, Gaynes BN, Hansen RA, Lux LJ, Krebs EE, Lohr KN, Gartlehner G. Depress Anxiety. 2012 Jun; 29(6):495-505. Epub 2012 May 2.
- Review [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].[Encephale. 2012]Review [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].Favré P. Encephale. 2012 Feb; 38(1):86-96. Epub 2011 Dec 10.
- Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depres...Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression
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