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.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 29477251 · doi:10.1016/S0140-6736(17)32802-7
What was done
A systematic review and random-effects network meta-analysis of published and unpublished double-blind randomized controlled trials (placebo-controlled and head-to-head) up to January 8, 2016. The study evaluated 21 antidepressants for acute treatment of adults (≥18 years) with major depressive disorder diagnosed by standard operationalized criteria. Trials with ≥20% of participants with bipolar disorder, psychotic depression, treatment-resistant depression, or serious concomitant medical illness were excluded. Primary outcomes were efficacy (response rate) and acceptability (all-cause discontinuation), reported as odds ratios (ORs) with 95% credible intervals (CrIs).
What was found
The review included 522 trials with 116,477 participants. All 21 antidepressants were more effective than placebo, with ORs ranging from 1.37 (95% CrI 1.16–1.63) for reboxetine to 2.13 (95% CrI 1.89–2.41) for amitriptyline. For acceptability versus placebo, only agomelatine (OR 0.84, 95% CrI 0.72–0.97) and fluoxetine (0.88, 0.80–0.96) had fewer dropouts, whereas clomipramine had higher dropouts (1.30, 1.01–1.68). In head-to-head trials, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (ORs 1.19–1.96), while agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable (ORs 0.43–0.77). Risk of bias was high in 46 trials (9%), moderate in 380 (73%), and low in 96 (18%); GRADE certainty was moderate to very low.
Why it matters
This comprehensive network meta-analysis demonstrates that all 21 assessed antidepressants outperform placebo for acute unipolar depression, providing comparative efficacy and tolerability rankings to guide clinical prescribing decisions.
Limits
Certainty of evidence was rated moderate to very low, with 82% of trials having moderate or high risk of bias. Findings are restricted to acute-phase treatment and exclude patients with treatment resistance, psychotic depression, bipolar disorder, or serious medical comorbidities. Most active-drug comparisons across the full network had wide credible intervals.
Cited by
- context SSRIs improve major depressive disorder by approximately 50% in randomized controlled trials.