Japanese experience with dual-action antidepressants.

Milnacipran is one of the first modern antidepressant drugs to be introduced into Japan, and the first dual-action antidepressant. Placebo-controlled clinical trials with this drug have demonstrated similar efficacy and superior tolerability to imipramine and mianserin. The good safety profile of the drug has been confirmed from open-label phase IV studies. There are indications, both from the randomized clinical trials and from the phase IV programme, that milnacipran may have a comparatively rapid onset of action, showing clear signs of efficacy after one week of treatment. This observation, which needs to be confirmed in an appropriately designed study, may be the clinical correlate of the rapid desensitization of 5-hydroxytryptamine (HT)1A receptors produced by milnacipran. A series of pilot studies have demonstrated the role of milnacipran in the management of certain affective disorders not adequately treated by classical antidepressants. These include bipolar disorder, treatment-resistant depression in the elderly and post-stroke depression. These findings merit confirmation in controlled studies, and open the way to using milnacipran to provide satisfactory treatment of these condi-