Cipriani A, et al. - During this study, researchers sought to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. When compared to placebo, all antidepressants were discovered to be more efficacious in adults with major depressive disorder. Findings unveiled minor variations between active drugs on the inclusion of placebo-controlled trials. On the other hand, greater variability was revealed in the efficacy and acceptability in head-to-head trials. Yielded data ought to serve evidence-based practice and inform patients, physicians, guideline developers, and policymakers on the considerable benefits of the different antidepressants.

Methods

• The scheme of this research was a systematic review and network meta-analysis.
• Data was analyzed from the 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MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016.
• 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 were included for this study.
• The exclusion criteria involved 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.
• Data was extracted after a predefined hierarchy and in network meta-analysis, group-level data were used.
• An inquiry was performed of the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence via the Grading of Recommendations Assessment, Development and Evaluation framework.
• Primary outcomes included efficacy (response rate) and acceptability (treatment discontinuations due to any cause).
• Using pairwise and network meta-analysis with random effects, the summary odds ratios (ORs) were computed.

Results

• A total of 28,552 citations were selected, among these 522 trials were included consisting of 116,477 subjects.
• 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, with regard to the efficacy.
• For acceptability, a connection was illustrated between only agomelatine (OR 0.84, 95% CrI 0.72-0.97) and fluoxetine (0.88, 0.80-0.96) with fewer dropouts than placebo.
• On the other hand, clomipramine appeared to be worse than placebo (1.30, 1.01-1.68).
• The range of variations in ORs between antidepressants was from 1.15 to 1.55 for efficacy and from 0.64 to 0.83 for acceptability, displaying wide CrIs on most of the comparative analyses.
• Head-to-head studies revealed the greater effectiveness of agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine compared to other antidepressants (range of ORs 1.19-1.96).
• In contrast, fluoxetine, fluvoxamine, reboxetine, and trazodone were discovered to be the least efficacious drugs (0.51-0.84).
• Greater tolerability was reported of agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine compared to other antidepressants (range of ORs 0.43-0.77) for acceptability.
• Data disclosed that amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine presented with the highest dropout rates (1.30-2.32).
• Herein, 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low, with moderate to very low certainty of evidence.