Levomilnacipran ER and Functional Efficacy in Major Depressive Disorder: A Pooled Analyses of 5 Double-Blind, Placebo-Controlled Trials
Objective: Data from 5 short-term studies (NCT00969709, NCT01377194, NCT00969150, NCT01034462, EudraCT:2006-002404-34) were analyzed to evaluate the effects of levomilnacipran ER (extended-release) on functional impairment associated with major depressive disorder (MDD).
Methods: Data from 5 randomized, double-blind, placebo-controlled trials evaluating levomilnacipran ER 40-120 mg/day (n=1566) vs placebo (n=1032) in patients with MDD were pooled. Functional improvement was measured by change from baseline to endpoint in Sheehan Disability Scale (SDS) total score in both the overall pooled population and demographic subgroups (age, sex); functional remission (SDS total score ≤6 and subscale scores ≤2) was also analyzed.
Results: In individual studies, levomilnacipran ER demonstrated significantly greater improvements than placebo in SDS total score in 4 of the 5 studies (LSMD -2.2 to -2.7; all 4 studies, P<.01); the difference was not significant in 1 study (-0.5; P=.562). In the pooled population, LSMD in SDS total score mean change from baseline to Week 8 was statistically significant for levomilnacipran ER vs placebo (-2.2; P<.0001); remission rates were also significantly higher for levomilnacipran ER (27%) vs placebo (20%; P=.0001). SDS improvement was statistically significant for levomilnacipran ER vs placebo in men (-2.5, P<.0001) and women (-2.0; P<.0001), and younger (18-54 years: -1.9, P<.0001) and older (≥55 years: -3.3, P<.0001) patients.
Conclusions: In pooled analyses of 5 placebo-controlled trials, statistically significant differences in functional improvement were seen in favor of levomilnacipran ER patients compared with placebo. Treatment differences in SDS scores and SDS remission rates demonstrate that levomilnacipran ER treatment decreased functional impairment associated with MDD.