Takeaway
- All antidepressants are more effective than placebo at treating adults with major depressive disorder, with significant variability in efficacy and acceptability between active drugs.
- More variability in head-to-head studies than placebo-controlled trials.
- A novel drug was significantly more effective than when the same treatment was used as control against a newer drug.
Why this matters
- This review provides an evidence-based guide to inform the choice of pharmacological treatment for adults with acute major depressive disorder.
Key results
- All antidepressants were more effective than placebo.
- Agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants, with odds ratios (ORs) ranging from 1·19 to 1·96.
- Fluoxetine, fluvoxamine, reboxetine, and trazodone were among the least efficacious drugs (ORs 0·51-0·84).
- Agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (ORs 0·43-0·77).
- Amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine were associated with the highest dropout rates (ORs 1·30-2·32).
- When all trials were considered, ORs were 1·15-1·55 for efficacy and 0·64-0·83 for acceptability, with wide credible intervals.
- In head-to-head comparisons, the newer drug was significantly more effective than when the same treatment was used as control against a newer drug.
- Adjusting for this novelty effect diminished differences between antidepressants.
Study design
- Systematic review and network meta-analysis of 522 eligible trials of 21 antidepressants and placebo comprising 116,477 participants.
- Funding: National Institute for Health Research Oxford Health Biomedical Research Centre, Japan Society for the Promotion of Science.
Limitations
- 82% of trials were at high or moderate risk of bias.
- Certainty of evidence was moderate to very low.
References
References
