Efficacy of levomilnacipran extended-release in improving functional impairment associated with major depressive disorder

Abstract

Major depressive disorder (MDD) is characterized by increased rates of impaired function and disability. During antidepressant treatment, functional improvement often lags behind symptomatic resolution, and residual impairment is associated with an increased risk for relapse. When evaluating MDD treatments, it is important to assess not only depressive symptoms but also functional outcomes. In this post-hoc analysis, data from five studies were pooled to examine the effect of levomilnacipran extended-release (ER) versus placebo on functional impairment as measured using the Sheehan Disability Scale. The mean change in the Sheehan Disability Scale total score was significantly greater for levomilnacipran ER versus placebo in the overall pooled population, for both sexes, and across all ages. Statistically significantly higher rates of functional response, functional remission, combined (functional and symptomatic) response, and combined remission were achieved with levomilnacipran ER compared with placebo in the pooled population, as well as in the male, female, younger, and middle-aged population subgroups. The levomilnacipran ER group also showed significantly improved functional outcomes versus placebo regardless of baseline depression severity. Similarly, functional impairment was significantly improved and higher functional and combined response and remission rates were achieved with levomilnacipran ER compared with placebo regardless of the baseline level of functional impairment.

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder

“…(2008) and Sheehan et al. (2011) and which has been used in other studies of MDD to define functional remission (Mancini et al., 2012; Montgomery, Mansuy, et al., 2014; Sambunaris, Bose, et al., 2014; Sambunaris, Gommoll, et al., 2014; Soares et al., 2014). …”

Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder

“…The primary efficacy measure was change from baseline to endpoint in MADRS total score; SDS total score change from baseline to endpoint was a prospectively defined secondary outcome (endpoint was either 8 weeks or 10 weeks, depending on study duration). The SDS scores were assessed at weeks 0, 4, 6, and 8 in the 8-week studies [25][26][27]29 and at weeks 0, 2, 4, 6, 8, and 10 in the 10-week study. 30…”

“…22 Reduced norepinephrine neurotransmission has been associated with low energy, problems concentrating, and functional impairment; therefore, antidepressants with significant noradrenergic effects may be effective in improving functional impairment in depressed patients. 23,24 A previous analysis 25 of pooled SDS data from 5 phase II/III studies of levomilnacipran ER in patients with MDD [26][27][28][29][30] found significantly greater mean improvements in functional impairment for levomilnacipran ER versus placebo on the SDS average total score and on all 3 SDS subscales, representing domains of work/school, social life, and family life/home responsibilities.…”

Cortical thickness increases with levomilnacipran treatment in a pilot randomised double‐blind placebo‐controlled trial in late‐life depression

“…Placebo‐controlled trials in younger adults with MDD suggest that LVM is well‐tolerated and significantly improves symptom severity and functioning . Daily doses range between 40 and 120 mg. Superior effects on depressive symptoms have been demonstrated in RCTs ranging from 8–12 weeks, especially at higher dosages .…”