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Review: differences in efficacy and acceptability exist for 12 new-generation antidepressants for major depression
Evidence-Based Medicine, 10/26/09

Usherwood T – In patients with major depression, new–generation antidepressants differ in efficacy and acceptability.

• Included studies were randomised controlled trials (RCTs) that compared any of 12 new–generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnaciprin, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine) as monotherapy for acute–phase treatment of major depression. Placebo groups and RCTs of postpartum depression were excluded. Outcomes were response and dropout rates at 8 weeks.
• Cochrane Collaboration Depression, Anxiety, and Neurosis Review Group’s controlled trials register (to Nov 2007) and reference lists were searched for RCTs. Pharmaceutical companies, regulatory agencies, and study investigators were contacted. 117 RCTs (n = 25 928; 64% women; 53 RCTs [n = 9321] had patients >65 y of age) were included. Mean study duration was 8 weeks (14 RCTs had >12 wks’ follow–up). 12 RCTs had adequate allocation concealment and blinding.

• When direct comparisons of antidepressants were pooled, differences existed in response rates for various comparisons.
• Direct comparisons for response favour escitalopram over citalopram; citalopram over reboxetine and paroxetine; mirtazapine over fluoxetine and venlafaxine; sertraline over fluoxetine; and venlafaxine over fluoxetine and fluvoxamine./li>
• Network meta–analysis, which included indirect comparisons, showed that escitalopram and sertraline have high efficacy and the best acceptability profile.
• Fluoxetine had fewer dropouts than reboxetine (number needed to treat [NNT] 13, 95% CI 8 to 74), and citalopram had fewer dropouts than sertraline (NNT 15, CI 9 to 255).

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