Lancet Review

Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis
Dr Andrea Cipriani et al
The Lancet, Volume 373, Issue 9665, Pages 746 - 758, 28 February 2009. Full text pdf

Summary
Background
Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants. We therefore did a multiple-treatments meta-analysis, which accounts for both direct and indirect comparisons, to assess the effects of 12 new-generation antidepressants on major depression.

Methods
We systematically reviewed 117 randomised controlled trials (25 928 participants) from 1991 up to Nov 30, 2007, which 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. The main outcomes were the proportion of patients who responded to or dropped out of the allocated treatment. Analysis was done on an intention-to-treat basis.

Findings
Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [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.

Interpretation
Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.

It expressed judgments about the relative efficacy and acceptability of different drugs, more clearly than the ACP papers.

Efficacy

The cumulative probabilities of being among the four most effective treatments were:

1) mirtazapine (24.4%),
2) escitalopram (23.7%),
3) venlafaxine (22.3%),
4) sertraline (20.3%),
5) citalopram (3.4%),
6) milnacipran (2.7%),
7) bupropion (2.0%),
8) duloxetine (0.9%),
9) fluvoxamine (0.7%),
10) paroxetine (0.1%),
11) fluoxetine (0.0%),
12) reboxetine (0.0%).

Acceptability

The cumulative probabilities of being among the four most acceptable treatments were:

1) escitalopram (27.6%),
2) sertraline (21.3%),
3) bupropion (19.3%),
4) citalopram (18.7%),
5) milnacipran (7.1%),
6) mirtazapine (4.4%),
7) fluoxetine (3.4%),
8) venlafaxine (0.9%),
9) duloxetine (0.7%),
10) fluvoxamine (0.4%),
11) paroxetine (0.2%),
12) reboxetine (0.1%).

Efficacy
Lower is better
Acceptibility
Higher is better

Bigger version

Ranking for efficacy (solid line) and acceptability (dotted line). Lines over on the left are better.
Ranking indicates the probability to be the best treatment, the second best, the third best, and so on, among the 12 antidepressants.

This makes the winners (escitalopram, sertraline, mirtazapine, and venlafaxine) obvious, but also illustrates how badly reboxetine and fluvoxamine do. I was surprised at the apparent difference between venlafaxine and duloxetine, which have seemed very similar to me, with, if anything, duloxetine having the advantage.