Levomilnacipran: A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder

Objective: To provide a clinical overview of the antidepressant levomilnacipran. Data Sources: Articles were identified by searching the MEDLINE, PubMed, Cochrane Library, and Clinicaltrials.gov databases through March 2014 using the keyword levomilnacipran. The manufacturer provided additional information from unpublished phase 11 and phase III trials. Study Selection and Data Extraction: Any clinical trial conducted for at least 3 weeks and published in the English language was selected for review. Additional documentation, including the product dossier, package insert, pharmacokinetic studies, and poster presentations supplied by the manufacturer, was also evaluated. Data Synthesis: Levonnilnacipran is the more potent enantiomer of milnacipran. It is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), dosed from 20 to 120 mg daily for the treatment of major depressive disorder (MDD). Efficacy and tolerability were established during 3 phase III randomized, double-blind placebo-controlled trials finding levomilnacipran to be significantly more efficacious than placebo in reduction of Montgomery-Asberg Depression Rating Scale scores. It is not known whether this agent is more efficacious than other antidepressants because direct comparison studies have not been conducted as of the time of this review. Conclusions: Levonnilnacipran demonstrates efficacy and tolerability for short-term treatment of MDD in adults. Available evidence does not strongly indicate that there is a specific subpopulation of patients who would benefit from levomilnacipran over currently available SNRIs. Full characterization of the agent's place in therapy alongside multiple other agents with similar mechanisms and efficacy requires trials with longer duration and active comparators.