Milnacipran /milnæsipræn/ (Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in the USA, but it is in other countries.
In a pooled analysis of 7 comparative trials with imipramine, milnacipran and imipramine were shown to have comparable efficacy while milnacipran was significantly better tolerated. A pooled analysis of studies comparing milnacipran and SSRIs concluded a superior efficacy for milnacipran with similar tolerability for milnacipran and SSRIs. A more recent meta-analysis of 6 studies involving more than 1,000 patients showed no distinction between milnacipran and SSRIs in efficacy or discontinuation rates, including discontinuation for side effects or lack of efficacy. A meta-analysis of a total of 16 randomized controlled trials with more than 2200 patients concluded that there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressant agents. However, compared with TCAs, significantly fewer patients taking milnacipran dropped out due to adverse events. As with other antidepressants, 1 to 3 weeks may elapse before significant antidepressant action becomes clinically evident.