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Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews
  1. Gerald Gartlehner1,2,
  2. Gernot Wagner1,
  3. Nina Matyas1,
  4. Viktoria Titscher1,
  5. Judith Greimel3,
  6. Linda Lux2,
  7. Bradley N Gaynes4,
  8. Meera Viswanathan2,
  9. Sheila Patel2,
  10. Kathleen N Lohr2
  1. 1 Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria
  2. 2 RTI-University of North Carolina Evidence-based Practice Center, RTI International, North Carolina, USA
  3. 3 University of Hohenheim, Stuttgart, Germany
  4. 4 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA
  1. Correspondence to Professor Gerald Gartlehner; gerald.gartlehner{at}


Objectives This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects.

Design This is a review of systematic reviews.

Data sources This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD.

Methods We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence.

Results Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: −0.35; 95% CI −0.31 to −0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28).

Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence).

Conclusions In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants.

Trial registration number International Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.

  • antidepressants
  • complementary and alternative medicine
  • cognitive behavioral therapy
  • psychological therapy
  • exercise
  • depression
  • systematic review.

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  • Contributors GG, KL and MV developed the concept of the study; GG, JG, GW, NM and VT conducted the literature review; GW, NM and VT abstracted data and conducted statistical analyses; MV and LL rated the risk of bias of included systematic reviews; GG, GW and NM graded the strength of evidence; BG provided clinical expertise throughout the study; GG and KL wrote the first draft of the manuscript; all authors reviewed the manuscript and provided comments and revisions.

  • Funding The paper was supported by internal funds from RTI International, Research Triangle Park, North Carolina.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The datasets used for meta-analyses are available from the corresponding author on reasonable request.

  • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with 'BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected theseerrors and the correct publishers have been inserted into the references.

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