A comprehensive meta-analysis of 12 new-generation antidepressants has shown sertraline and escitalopram have clear advantages in terms of efficacy and acceptability, while reboxetine was shown to be the significantly less efficacious than the other 11 drugs. The findings appear in an Article published Online First and in an upcoming edition of The Lancet, written by Dr Andrea Cipriani, University of Verona, Italy, and colleagues.

The study analysed results of 117 randomised controlled trials from 1991-2007, which compared the effects of these antidepressants in more than 25,000 patients with major depression. The drugs tested were 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.

Sertraline and escitalopram were found to be the best antidepressants overall in terms of efficacy and acceptability. Sertraline was more efficacious than duloxetine (by 30%), than both duloxetine and fluvoxamine (by 27% for both), 25% fluoxetine (by 25%), paroxetine (by 22%), reboxetine (by 85%). Escilatopram was more efficacious than duloxetine (by 33%), fluoxetine (by 32%), fluvoxamine (by 35%), paroxetine (by 30%), and reboxetine (by 95%). As with sertraline and escitalopram, mirtazapine and venlafaxine were also more efficacious than these other drugs. However, escilatopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations of treatment than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.

The authors conclude: "The most important clinical implication of the results is that escitalopram and sertraline might be the best choice when starting a treatment for moderate to severe major depression because they have the best possible balance between efficacy and acceptability."

They add: "Sertraline seems to be better than escitalopram because of its lower cost in most countries. However, in the absence of a full economic model, this recommendation cannot be made unequivocally because several other costs are associated with the use of antidepressants."

In an accompanying Comment, Dr Sagar V Parikh, Department of Psychiatry, University of Toronto and University Health Network, Toronto, ON, Canada, says: "A key challenge now involves the issue of costs and benefits; while the generic agents are cheaper to buy, proper studies are needed to aid societal choices among the four strongest antidepressants. As Cipriani and colleagues have emphasised, such cost concerns are particularly crucial from a global perspective, because most people live in low-income and middle-income countries."

Tony Kirby
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