Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews
Open accessAbstract
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.
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Patients may discontinue chronic treatment due to lack of rapid and consistent treatment benefits, treatment-related adverse events, and expectations of treatment that are misaligned with the treatment goals of HCPs.
“Patients may discontinue chronic treatment due to lack of rapid and consistent treatment benefits, 37 treatmentrelated adverse events (AEs), [37][38][39][40] and expectations of treatment that are misaligned with the treatment goals of HCPs.41,42”
From Digital health technologies and major depressive disorder (2023) · cites this paper as [40]
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- Authors
- Gartlehner, G., Wagner, G., Matyas, N., Titscher, V., Greimel, J., Lux, L., Gaynes, B. N., Viswanathan, M., Patel, S., & Lohr, K. N.
- Affiliations
- Universität für Weiterbildung Krems (AT)
- University of Hohenheim (DE)
- RTI International (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Gartlehner, Gerald
- ORCID
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2017-06
- Volume
- 7
- Issue
- 6
- Pages
- e014912
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC5623437
- OpenAlex
- W2643196631
- Cited by
- 192
- References
- 56
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 36 · 2023: 23 · 2022: 28 · 2021: 25 · 2020: 21 · 2019: 11 · 2018: 8 · 2017: 1
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- RTI International, Research Triangle Park, North Carolina
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, antidepressants, second-generation antidepressants, cognitive behavioral therapy, non-pharmacological treatment, treatment efficacy, adverse events, quality of evidence, risk of bias
- MeSH terms
- Clinical Decision-Making, Systematic Reviews as Topic, Adult, Major Depressive Disorder, Humans, Meta-Analysis as Topic, Cognitive Behavioral Therapy, Randomized Controlled Trials as Topic, Antidepressive Agents, Second-Generation
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