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Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of PhysiciansBenefits and Harms of Treatments for Major Depression

Gerald Gartlehner, MD, MPH; Bradley N. Gaynes, MD, MPH; Halle R. Amick, MSPH; Gary N. Asher, MD, MPH; Laura C. Morgan, MA; Emmanuel Coker-Schwimmer, MPH; Catherine Forneris, PhD, ABPP; Erin Boland, BA; Linda J. Lux, PhD; Susan Gaylord, PhD; Carla Bann, PhD; Christiane Barbara Pierl, PhD, MPH; and Kathleen N. Lohr, PhD, MPhil, MA
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 9 February 2016.


From RTI International, Research Triangle Park, and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, and Danube University, Krems, Austria.

Disclaimer: The authors of this report are responsible for its content. Statements in this manuscript should not be construed as endorsement by the AHRQ or the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank Aysegul Gozu, MD, MPH, from the AHRQ; Meera Viswanathan, PhD, and Loraine Monroe, from RTI International, for dedicated support; and Irma Klerings, from Danube University, Krems, for literature searches.

Grant Support: By contract 290-2012-00008i from the AHRQ to RTI International.

Disclosures: Dr. Gartlehner reports a contract with the Agency for Healthcare Research and Quality during the conduct of the study. Dr. Gaynes reports grants from the Agency for Healthcare Research and Quality during the conduct of the study. Ms. Amick reports that this work was funded by the Agency for Healthcare Research and Quality. Dr. Forneris reports salary support from the Agency for Healthcare Research and Quality during the conduct of the study. Dr. Gaylord reports grants and payment for writing or reviewing the manuscript from the Agency for Healthcare Research and Quality and consultancies and grants/grants pending from the National Institutes of Health. Dr. Lohr reports a contract from RTI International during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1813.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol: Available at http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1923&pageaction=displayproduct. Statistical code: Not applicable. Data set: Available from the AHRQ Systematic Review Data Repository (http://srdr.ahrq.gov/) and upon request from Dr. Gartlehner (e-mail, gerald.gartlehner@donau-uni.ac.at).

Requests for Single Reprints: Gerald Gartlehner, MD, MPH, Danube University, Dr. Karl Dorrek Strasse 30, 3500 Krems, Austria; e-mail, gerald.gartlehner@donau-uni.ac.at.

Current Author Addresses: Dr. Gartlehner: Danube University, Dr. Karl Dorrek Strasse 30, 3500 Krems, Austria.

Drs. Gaynes and Forneris: Department of Psychiatry, University of North Carolina at Chapel Hill, 101 Manning Drive, CB #7160, Chapel Hill, NC 27599.

Ms. Amick and Mr. Coker-Schwimmer: Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 725 Martin Luther King Jr. Boulevard, Chapel Hill, NC 27599.

Dr. Asher: Department of Family Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, CB #7160, Chapel Hill, NC 27599.

Ms. Morgan, Ms. Boland, Ms. Lux, and Drs. Bann and Lohr: RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709.

Dr. Gaylord: Department of Physical Medicine and Rehabilitation, University of North Carolina at Chapel Hill, 101 Manning Drive, CB #7160, Chapel Hill, NC 27599.

Dr. Pierl: Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Dr. Karl Dorrek Strasse 30, 3500 Krems, Austria.

Author Contributions: Conception and design: G. Gartlehner, B.N. Gaynes, G.N. Asher, L.C. Morgan, L.J. Lux.

Analysis and interpretation of the data: G. Gartlehner, B.N. Gaynes, H.R. Amick, G.N. Asher, L.C. Morgan, E. Coker-Schwimmer, C. Forneris, E. Boland, S. Gaylord, C. Bann, K.N. Lohr.

Drafting of the article: G. Gartlehner, B.N. Gaynes, H.R. Amick, G.N. Asher, L.C. Morgan, E. Coker-Schwimmer, E. Boland, S. Gaylord, C. Bann, C.B. Pierl, K.N. Lohr.

Critical revision of the article for important intellectual content: G. Gartlehner, B.N. Gaynes, H.R. Amick, G.N. Asher, L.C. Morgan, E. Coker-Schwimmer, E. Boland, L.J. Lux, C. Bann, C.B. Pierl, K.N. Lohr.

Final approval of the article: G. Gartlehner, B.N. Gaynes, H.R. Amick, G.N. Asher, C. Forneris, C. Bann, K.N. Lohr.

Statistical expertise: B.N. Gaynes, C. Bann.

Obtaining of funding: G. Gartlehner, B.N. Gaynes.

Administrative, technical, or logistic support: B.N. Gaynes, L.C. Morgan, E. Boland, L.J. Lux.

Collection and assembly of data: G. Gartlehner, B.N. Gaynes, H.R. Amick, G.N. Asher, L.C. Morgan, E. Coker-Schwimmer, C. Forneris, E. Boland, L.J. Lux, S. Gaylord, C. Bann, C.B. Pierl.


Ann Intern Med. 2016;164(5):331-341. doi:10.7326/M15-1813
Text Size: A A A

Background: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear.

Purpose: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD.

Data Sources: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research.

Study Selection: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms.

Data Extraction: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings.

Data Synthesis: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief.

Limitation: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence.

Conclusion: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD.

Primary Funding Source: Agency for Healthcare Research and Quality.

Figures

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Appendix Figure.

Summary of evidence search and selection.

KQ = key question; MA = meta-analysis; SR = systematic review.

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Figure 1.

Comparison of response rates of SGAs with other eligible interventions.

CAM = complementary and alternative medicine; CBT = cognitive behavioral therapy; SGA = second-generation antidepressant; SOE = strength of evidence.

* Estimate is based on trial with lowest risk of bias.

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Figure 2.

Comparison of remission rates of SGAs with other eligible interventions.

CAM = complementary and alternative medicine; CBT = cognitive behavioral therapy; SGA = second-generation antidepressant; SOE = strength of evidence.

* Estimate is based on trial with lowest risk of bias.

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Figure 3.

Comparison of discontinuation rates because of adverse events of SGAs with other eligible interventions.

CAM = complementary and alternative medicine; CBT = cognitive behavioral therapy; SGA = second-generation antidepressant; SOE = strength of evidence.

* Estimate is based on trial with lowest risk of bias.

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Cognitive Behavioural Therapy and depression: the US and the rest of the world
Posted on March 2, 2016
Alain Brallion, MD, PhD, Jérémy FONSECA DAS NEVES MPsy, Francoise TAIEBI MPsy
University Hospital, Amiens, France
Conflict of Interest: None Declared
The Clinical Practice Guideline from the American College of Physicians concluded that cognitive behavioural therapy (CBT) and antidepressants “are both viable choices due to similar efficacy”.(1) This deserves comment.
First, the safety issue cannot be ignored when choosing a treatment and the Food and Drug Administration issued in 2004 a black-box warning indicating that antidepressants were associated with an increased risk of suicidal thinking, feeling, and behavior in young people.
Second, in other countries clinical practice may be different as the accessing psychotherapy remains a problem. Eg, in France not only the Clinical Practice Guideline about depression was issued in 2002 (not updated yet …) by the High Authority for Health but the mandatory and costly health insurance scheme does not reimburse care by licensed clinical psychologists. This may explain why Pubmed searches for “Cognitive Behavioural Therapy” with “depression” hit 3 articles when adding France and 285 when adding UK, a comparable country where care by licensed clinical psychologists is reimbursed.
The World Health Organization projected that depression will be the leading cause of disease burden worldwide by 2030.(2) Already in 1996, WHO viewed depression would be a worldwide epidemic that within twenty years will be second only to cardiovascular disease as the world’s most debilitating disease.(3) WHO’s new prediction may be right for once as the DSM V removed the bereavement exclusion from the diagnosis of major depression. CBT could decrease the important financial, personal, and interpersonal burdens of this illness without potential adverse effects. Sadly, in too many countries there is no teaching of basic CBT for physicians and it is so easy in a ten minute appointment to prescribe an antidepressant. Well-designed randomized controlled trials about CBT and depression began in the mid 90’s.(4) It may be time for moving forward as long term cost-effectiveness is now evidence based, even for treatment-resistant depression in the primary care setting.(5)

1 Gartlehner G, Gaynes BN, Amick HR, Asher GN, Morgan LC, Coker-Schwimmer E, et al. Comparative benefits and harms of antidepressant, psychological, complementary, and exercise treatments for major depression: an evidence report for a clinical Practice Guideline from the American College of Physicians. Ann Intern Med 2016;164:331-341.
2 Lépine JP, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat 2011;7(suppl 1):3-7
3 Summerfield D. Depression: epidemic or pseudo-epidemic? J R Soc Med 2006;99: 161–162.
4 Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE. Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1998;129:613-21.
5 Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial. Lancet Psychiatry 2016. Published online February 2016.
Sex and Gender Matters
Posted on March 8, 2016
Eva Rasky, Sylvia Groth
Institute of Social Medicine and Epidemiology, Medical University Graz
Conflict of Interest: None Declared
Dear Editor,
The evidence report by Gartlehner et al. (1) finely compares comparative harms and benefits of four different treatment options for major depression of persons, a well done and needed study. However, the limitation section does not include a note on possibly implicit sex and gender biases.
Major depression is a disease with documented sex differences in incidence and in effects of antidepressants. Difference in usage of antidepressants, psychological, complementary, and exercise treatment may be related to gender. Despite evidence that sex and gender matter to health outcome, data and analysis related to sex and gender are frequently absent in systematic reviews (2).
This is surprisingly also true for this evidence report. Occasional information on sex is given without relating it to interventions and outcome. The International Committee of Medical Journal Editors (3) and the European Association of Science Editors (4) issued recommendations and guidelines to include data on sex and gender distribution as well as sex disaggregated analysis in all studies published. Only a clearly formulated search strategy will result in locating studies including sex and gender data and analysis (5). An absence of studies should also be documented. Therefore, it seems sensible that the authors provide sex disaggregated data and analysis systematically and throughout the evidence report. Did they apply specific search strategies looking for sex and gender specifics and what were the results? When it comes to evidence and in order to ensure the quality of scientific research the variables sex and gender need to be systematically considered, the results published. This improves the data base, health outcomes and ensures health equity for all persons. Persons are not neuter, but mostly, male or female, and this matters.

Éva Rásky, Institute of Social Medicine, Medical University Graz, Universitätsstraße 6/I, 8010 Graz, Austria
Sylvia Groth, Women´s Health Activist, Graz, Email: sylviagroth@gmx.at

1 Gerald Gartlehner, MD, MPH; Bradley N. Gaynes, MD, MPH; Halle R. Amick, MSPH; et al. Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatment for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016; 164(5): 331-341. doi:10.7326/M15-1813.
2 Runnels V, Tudiver S, Doull M, Boscoe M. The challenges of including sex/gender analysis in systematic reviews: a qualitative survey. Systematic Reviews 2014; 3:33. http://www.systematicreviewsjournal.com/content/3/1/33 on 6th March 2016.
3 International Committee of Medical Journal Editors (ICMJE). Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals. Updated 2015; 1-17. http://www.icmje.org/icmje-recommendations.pdf on 6th March 2016.
4 European Association of Science Editors (EASE). Sex and gender equity in research guidelines. 6th World Congress on Women´s Mental Health, Tokyo, Japan, 2015. http://www.ease.org.uk/sites/default/files/ease_gpc_wcwmh_s.heidari_2015-03-01_v1.pdf on 6th March 2016.
5 Moerman CJ, Deurenberg R, Haafkens JA. Locating sex-specific evidence on clinical questions in MEDLINE: a search filter for use on OvidSP™. BMC Medical Research Methodology 2009; 9: 25. DOI: 10.1186/1471-2288-9-25.
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