Article

Efficacy and Safety of Levomilnacipran Sustained Release in Moderate to Severe Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study

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The Journal of Clinical Psychiatry (Impact Factor: 5.5). 04/2013; 74(4):363-9. DOI: 10.4088/JCP.12m08141
Source: PubMed

ABSTRACT

To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD).
Between December 2006 and October 2007, a 10-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, flexible-dose trial assessed once-daily levomilnacipran SR (75 mg or 100 mg) in outpatients (18-70 years) meeting DSM-IV criteria for a major depressive episode (duration ≥ 1 month) with a 17-item Hamilton Depression Rating Scale (HDRS17) score > 22 and Sheehan Disability Scale (SDS) score ≥ 10. Levomilnacipran SR dose was increased to 100 mg/d over 12 days. The primary efficacy measure was Montgomery Asberg Depression Rating Scale (MADRS) score change from baseline to week 10; secondary efficacy measures were the HDRS17, SDS, Clinical Global Impressions-Improvement scale, and MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10). Safety was evaluated according to adverse events, laboratory investigations, and vital signs/physical findings.
Efficacy analyses included 276 levomilnacipran SR-treated patients and 277 placebo-treated patients. Levomilnacipran SR was significantly superior to placebo on MADRS total score change from baseline to week 10 (least squares mean difference [LSMD] = -4.2 [95% CI, -5.7 to -2.6]; P < .0001). Statistical significance in favor of levomilnacipran SR was demonstrated on change from baseline to week 10 in HDRS17 total score (LSMD = -3.4 [95% CI, -4.7 to -2.2]; P < .0001) and SDS total score (LSMD = -3.4 [95% CI, -4.6 to -2.2]; P < .0001) and subscales. Significantly more levomilnacipran SR patients versus placebo patients achieved MADRS response (59.1% vs 42.2%; P < .0001) and remission (46.4% vs 26.0%; P < .0001). Levomilnacipran SR was generally safe and well tolerated; more levomilnacipran SR patients (9.4%) versus placebo patients (6.5%) discontinued due to adverse events, but more placebo patients versus levomilnacipran SR patients discontinued overall (24.9% vs 20.2%).
Levomilnacipran SR demonstrated robust efficacy on all measures and was generally well tolerated.
EudraCT number: 2006-002404-34.

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    • "randomized, double-blind, placebo-controlled trials have been conducted to evaluate the efficacy and safety of levomilnacipran ER in adults with MDD (Asnis et al., 2013; Montgomery et al., 2013; Bakish et al., 2014; Gommoll et al., 2014; Sambunaris et al., 2014a). In all of these studies, the primary and secondary efficacy parameters were defined as change from baseline in "
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    • "The efficacy and safety of levomilnacipran ER in the treatment of MDD have been evaluated in five phase II/III studies, four of which have met the prespecified primary efficacy outcome (Asnis et al., 2013; Montgomery et al., 2013; Bakish et al., 2014; Gommoll et al., 2014; Sambunaris et al., 2014). In this post-hoc analysis, data from all five phase II and III studies (Fig. 1) have been pooled to examine the effect of levomilnacipran ER versus placebo on functional impairment as measured using the Sheehan Disability Scale (SDS; Sheehan et al., 1996). "
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