The clinical efficacy of milnacipran, a selective serotonin and noradrenaline reuptake inhibitor, was reviewed on the basis of three, multicentre, placebo-controlled trials in major depression. A dose-range study showed the superiority of milnacipran at 50 or 100 mg twice a day compared with placebo whereas the effect of 25 mg twice a day was not clearly distinguished from that of placebo. This has been confirmed by other studies where the 50-mg twice-a-day regimen was shown to be significantly more efficacious than placebo on all outcome measures (Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression). The positive results in the individual studies were supported by a meta-analysis of the data from the three studies. A subgroup analysis of hospitalized patients in the meta-analysis showed an advantage for milnacipran, suggesting that milnacipran is effective in more severe depression.