Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study.

Abstract

BACKGROUND:

Major depressive disorder (MDD) is a global health concern. This study examined the efficacy, safety and tolerability of an extended-release (ER) formulation of levomilnacipran, an antidepressant approved for the treatment of MDD in adults.

METHODS:

This 10-week (1-week placebo run-in period, 8-week double-blind treatment, 1-week down-taper), multicentre, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted between June 2011 and March 2012. Adult outpatients (age 18-75 yr) with MDD were randomly assigned (1:1:1) to placebo or to levomilnacipran ER 40 mg/day or 80 mg/day. For primary efficacy, we analyzed the Montgomery-Åsberg Depression Rating Scale (MADRS) change from baseline to week 8 using a mixed-effects model for repeated-measures approach on the intent-to-treat (ITT) population. For secondary efficacy, we used the Sheehan Disability Scale (SDS), and for safety, we examined adverse events and laboratory, vital sign/physical and electrocardiography findings.

RESULTS:

The ITT population consisted of 185 patients in the placebo group, 185 in the levomilnacipran ER 40 mg/day group and 187 in the levomilnacipran ER 80 mg/day group. Study completion rates were similar among the groups (76%-83%). On MADRS change from baseline the least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo was significant for levomilnacipran ER 40 mg/day (-3.3 [-5.5 to -1.1], p = 0.003) and 80 mg/day (-3.1, [-5.3 to -1.0], p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg/day (-1.8, 95% [-3.6 to 0], p = 0.046) and 80 mg/day (-2.7 [-4.5 to -0.9], p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (≥ 5% and ≥ double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness, hyperhidrosis, urinary hesitation and erectile dysfunction.

LIMITATIONS:

Limitations to our study included short treatment duration and lack of an active control arm.

CONCLUSION:

Levomilnacipran ER at doses of 40 mg/day and 80 mg/day demonstrated efficacy on symptomatic and functional measures of MDD and was generally well tolerated in this patient population.

CLINICAL TRIAL REGISTRATION:

NCT01377194.

• Authors: David Bakish, Anjana Bose, Carl Gommoll, Changzheng Chen, Rene Nunez, William M Greenberg, Michael Liebowitz, Arif Khan
• Journal: Journal of psychiatry & neuroscience : JPN (J Psychiatry Neurosci) Vol. 39 Issue 1 Pg. 40-9 (Jan 2014) ISSN: 1488-2434 [Electronic] Canada
• PMID: 24144196 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents
• Cyclopropanes
• Milnacipran

Topics

• Adolescent
• Adult
• Aged
• Antidepressive Agents (administration & dosage, adverse effects)
• Cyclopropanes (administration & dosage, adverse effects)
• Depressive Disorder, Major (drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Milnacipran
• Psychiatric Status Rating Scales
• Treatment Outcome
• Young Adult