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Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h6019 (Published 08 December 2015) Cite this as: BMJ 2015;351:h6019
  1. Halle R Amick, research associate1,
  2. Gerald Gartlehner, associate director2, department chair and professor3,
  3. Bradley N Gaynes, professor and associate chair of research training4,
  4. Catherine Forneris, professor4,
  5. Gary N Asher, assistant professor5,
  6. Laura C Morgan, research public health analyst2,
  7. Emmanuel Coker-Schwimmer, research assistant1,
  8. Erin Boland, public health analyst2,
  9. Linda J Lux, senior health analyst2,
  10. Susan Gaylord, associate professor and director of the program on integrative medicine6,
  11. Carla Bann, fellow (statistics and psychometrics)2,
  12. Christiane Barbara Pierl, fellow (epidemiology)3,
  13. Kathleen N Lohr, distinguished fellow (health care services)2
  1. 1Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 725 Martin Luther King Jr Boulevard, Chapel Hill, NC 27599, USA
  2. 2RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA
  3. 3Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, 3500 Krems, Austria
  4. 4Department of Psychiatry, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
  5. 5Department of Family Medicine, University of North Carolina at Chapel Hill, 590 Manning Drive, Chapel Hill, NC 27599, USA
  6. 6Department of Physical Medicine and Rehabilitation, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
  1. Correspondence to: H R Amick amick@med.unc.edu
  • Accepted 24 October 2015

Abstract

Study question What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults?

Methods This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT.

Summary answer and limitations Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings.

What this study adds Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences.

Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Footnotes

  • We thank Meera Viswanathan and Loraine Monroe, both from RTI International, for dedicated support and Irma Klerings from Danube University, Krems, for literature searches.

  • Contributors: HRA reviewed studies for inclusion and exclusion; entered, cleaned, and analyzed the data; did statistical analyses; and drafted and revised the paper. GG oversaw the design and conduct of the full report from which this manuscript was devised, reviewed included studies, analyzed data, and revised the draft paper. BNG, CF, GNA, LCM, EC-S, EB, LJL, SG, CB, and CBP participated fully in the report from which this manuscript was devised, reviewed included studies, entered and cleaned data, and revised the draft paper. BNG, LCM, and CB also did data analyses. KNL contributed to the full report from which this project was based and revised the draft paper. HRA is the guarantor.

  • Funding: This project was funded under contract 290-2012-00008i from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. The authors of this manuscript are responsible for its content. Statements in this manuscript should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services.

  • Competing interests: The authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization other than the funding agency listed above for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not needed for this project.

  • Data sharing: Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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