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Cited by 330Treatment of Major DepressionMental Health Treatment and AccessPsychotherapy Techniques and Applications

Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis

Open access
Cipriani, Andrea, Furukawa, Toshi A, Salanti, Georgia, Chaimani, Anna, Atkinson, Lauren Z, Ogawa, Yusuke, Leucht, Stefan, Ruhe, Henricus G +10 more·2018·Focus
DOI 10.1176/appi.focus.16407PMC PMC6996085
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Abstract

Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies’ risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2.13 (95% credible interval [CrI] 1.89–2.41) for amitriptyline and 1.37 (1.16–1.63) for reboxetine. For acceptability, only agomelatine (OR 0.84, 95% CrI 0.72–0.97) and fluoxetine (0.88, 0.80–0.96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1.30, 1.01–1.68). When all trials were considered, differences in ORs between antidepressants ranged from 1.15 to 1.55 for efficacy and from 0.64 to 0.83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1.19–1.96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0.51–0.84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0.43–0.77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1.30–2.32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. (Reprinted with permission from Lancet 2018; 391:1357-66)

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Authors
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Cipriani, Andrea
ORCID
Venue
Focus
Publisher
American Psychiatric Association Publishing
Published
2018-10
Volume
16
Issue
4
Pages
420-429
ISSN
  • 1541-4094 (ISSN-L)
  • 1541-4108
DOI
10.1176/appi.focus.16407
PMC
PMC6996085
OpenAlex
W3210887564
Cited by
328
References
31
Citations by year
2026: 17 · 2025: 36 · 2024: 52 · 2023: 61 · 2022: 42 · 2021: 64 · 2020: 27 · 2019: 21 · 2018: 7
FWCI
3.47
Type
journal article
Language
en
Open access
Locations
  • FOCUS The Journal of Lifelong Learning in Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute for Health and Care Research (BRC‐1215‐20005)
  • Japan Society for the Promotion of Science (17K19808)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
major depressive disorder, antidepressants, acute treatment, antidepressant efficacy, treatment discontinuation, placebo response, amitriptyline, reboxetine, agomelatine, fluoxetine, venlafaxine, escitalopram, mirtazapine, paroxetine, sertraline, bupropion

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