A meta-analysis of comparative efficacy and acceptability of new-generation antidepressants

Evidence Summaries

Level of Evidence = B
Sertraline appears to have the most favourable balance between benefits and acceptability in the treatment of major depression.
Consider using sertraline in acute phase of major depression.

A systematic review 1 included 117 studies with a total of 25,928 subjects. The trials compared any of the following antidepressants at therapeutic dose range for the acute treatment of unipolar major depression in adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. Acute treatment was defined as 8-week treatment for the analyses. Inequalities in dosing, that could affect comparative efficacy, were taken into consideration. The main outcomes were the proportion of patients who responded to or dropped out of the treatment. Analysis was done on an intention-to-treat basis. Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (OR 1,39, 1,33, 1,30 and 1,27, respectively), fluoxetine (1,37, 1,32, 1,28, and 1,25, respectively), fluvoxamine (1,41, 1,35, 1,30, and 1,27, respectively), paroxetine (1,35, 1,30, 1,27, and 1,22, respectively), and reboxetine (2,03, 1,95, 1,89, and 1,85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.

Comment: The quality of evidence is downgraded by suspected publication bias (mostly commercially funded studies).


1. Cipriani A, Furukawa TA, Salanti G et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009;373(9665):746-58.  [PMID:19185342]

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