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      Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews

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          Abstract

          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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          Most cited references42

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          How quickly do systematic reviews go out of date? A survival analysis.

          Kaveh Shojania, Margaret Sampson, Mohammed T Ansari … (2007)
          Systematic reviews are often advocated as the best source of evidence to guide clinical decisions and health care policy, yet we know little about the extent to which they require updating. To estimate the average time to changes in evidence that are sufficiently important to warrant updating systematic reviews. Survival analysis of 100 quantitative systematic reviews. Systematic reviews published from 1995 to 2005 and indexed in ACP Journal Club. Eligible reviews evaluated a specific drug or class of drug, device, or procedure and included only randomized or quasi-randomized, controlled trials. Quantitative signals for updating were changes in statistical significance or relative changes in effect magnitude of at least 50% involving 1 of the primary outcomes of the original systematic review or any mortality outcome. Qualitative signals included substantial differences in characterizations of effectiveness, new information about harm, and caveats about the previously reported findings that would affect clinical decision making. The cohort of 100 systematic reviews included a median of 13 studies and 2663 participants per review. A qualitative or quantitative signal for updating occurred for 57% of reviews (95% CI, 47% to 67%). Median duration of survival free of a signal for updating was 5.5 years (CI, 4.6 to 7.6 years). However, a signal occurred within 2 years for 23% of reviews and within 1 year for 15%. In 7%, a signal had already occurred at the time of publication. Only 4% of reviews had a signal within 1 year of the end of the reported search period; 11% had a signal within 2 years of the search. Shorter survival was associated with cardiovascular topics (hazard ratio, 2.70 [CI, 1.36 to 5.34]) and heterogeneity in the original review (hazard ratio, 2.15 [CI, 1.12 to 4.11]). Judgments of the need for updating were made without involving content experts. In a cohort of high-quality systematic reviews directly relevant to clinical practice, signals for updating occurred frequently and within a relatively short time.
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            Behavioural Activation for Depression; An Update of Meta-Analysis of Effectiveness and Sub Group Analysis

            David Ekers, Lisa Webster, Annemieke Van Straten … (2014)
            Background Depression is a common, disabling condition for which psychological treatments are recommended. Behavioural activation has attracted increased interest in recent years. It has been over 5 years since our meta-analyses summarised the evidence supporting and this systematic review updates those findings and examines moderators of treatment effect. Method Randomised trials of behavioural activation for depression versus controls or anti-depressant medication were identified using electronic database searches, previous reviews and reference lists. Data on symptom level and study level moderators were extracted and analysed using meta-analysis, sub-group analysis and meta-regression respectively. Results Twenty six randomised controlled trials including 1524 subjects were included in this meta-analysis. A random effects meta-analysis of symptom level post treatment showed behavioural activation to be superior to controls (SMD −0.74 CI −0.91 to −0.56, k = 25, N = 1088) and medication (SMD −0.42 CI −0.83 to-0.00, k = 4, N = 283). Study quality was low in the majority of studies and follow- up time periods short. There was no indication of publication bias and subgroup analysis showed limited association between moderators and effect size. Conclusions The results in this meta-analysis support and strengthen the evidence base indicating Behavioural Activation is an effective treatment for depression. Further high quality research with longer term follow-up is needed to strengthen the evidence base.
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              Physical exercise intervention in depressive disorders: meta-analysis and systematic review.

              M Lindwall, T. Archer, T Josefsson (2014)
              Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2017
                Publication date (Electronic): 14 June 2017
                Volume: 7
                Issue: 6
                Electronic Location Identifier: e014912
                Affiliations
                [1 ] departmentDepartment for Evidence-based Medicine and Clinical Epidemiology , Danube University Krems , Krems, Austria
                [2 ] RTI-University of North Carolina Evidence-based Practice Center, RTI International , North Carolina, USA
                [3 ] University of Hohenheim , Stuttgart, Germany
                [4 ] departmentDepartment of Psychiatry , University of North Carolina at Chapel Hill , Chapel Hill, USA
                Author notes
                [Correspondence to ] Professor Gerald Gartlehner; gerald.gartlehner@ 123456donau-uni.ac.at
                Article
                Publisher ID: bmjopen-2016-014912
                DOI: 10.1136/bmjopen-2016-014912
                PMC ID: 5623437
                PubMed ID: 28615268
                SO-VID: 90a889b2-43d2-42db-a576-9a1f63d30f48
                Copyright © © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                Date received : 01 November 2016
                Date revision received : 16 March 2017
                Date accepted : 27 April 2017
                Funding
                Funded by: RTI International, Research Triangle Park, North Carolina;
                Categories
                Subject: Mental Health
                Subject: Research
                Subject: 1506
                Subject: 1712
                Custom metadata
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                ScienceOpen disciplines: Medicine
                Keywords: antidepressants,complementary and alternative medicine,cognitive behavioral therapy,psychological therapy,exercise,depression,systematic review.
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: antidepressants, complementary and alternative medicine, cognitive behavioral therapy, psychological therapy, exercise, depression, systematic review.

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