Levomilnacipran is a potent, selective serotonin and norepinephrine reuptake inhibitor (SNRI) that is approved for the treatment of major depressive disorder (MDD) in adults.
Levomilnacipran (1S, 2R-) is the most active enantiomer of the racemate, milnacipran, which is approved in the U.S. for the management of fibromyalgia and in Europe and Japan for the treatment of MDD. An extended-release (ER) formulation of levomilnacipran has been developed for once-daily use. The safety and efficacy of levomilnacipran ER in the treatment of MDD in adults was evaluated in five Phase II/III clinical studies.
Levomilnacipran ER was generally safe and well tolerated in these studies. For efficacy, the mean change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS), significantly greater decreases were observed for levomilnacipran ER compared to placebo in two fixed-dose and two flexible-dose studies. Significant differences from placebo were also observed on the secondary endpoint, the Sheehan Disability Scale (SDS) total score.
In the final study, a flexible dose study, differences between levomilnacipran ER and placebo showed numerical benefits on MADRS and SDS, but this did not reach statistical significance. To better assess the efficacy of levomilnacipran ER in the treatment of MDD, data from the five studies were recently pooled and analyzed by patient subgroups. The total population included 2598 patients (placebo, 1032; levomilnacipran ER, 1566).
Baseline characteristics were the same between treatment groups. In the overall population, the percentage of patients meeting the MADRS criterion for treatment response was higher with levomilnacipran ER than with placebo, 10.2% (p<0.001); similar benefits for levomilnacipran ER compared with placebo were seen in most patient subgroups. Response rates were notably higher for levomilnacipran ER versus placebo in patients who were ≥ 60 years of age (17.9% difference), who reported ≥ 5 prior depressive episodes (14.6% difference), or who had a baseline MADRS total score <30 (14.1% difference) (p<0.001 in all cases).
The difference between levomilnacipran ER and placebo in remission rates was 6.2% (p <0.05) in the overall population; similar benefits for levomilnacipran ER versus placebo were generally observed in most patient subgroups. Differences in remission rates between active treatment and placebo were relatively high in patients with a baseline MADRS score <30 (19.9% difference; p <0.001).
The NNT for remission in the overall population was 17. An NNT of 5 was found in patients with a baseline MADRS total score <30. NNTs of 11 to 20 were found in 11 subgroups, whereas NNTs in the remaining subgroups varied considerably. The pooled analysis concluded that levomilnacipran ER was effective in a wide range of patients with MDD, including men and women, aged 18 to 78 years, with varying histories and severity of symptoms.