Title:The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review
Volume: 14
Issue: 2
Author(s): Antonio Bruno, Paolo Morabito, Edoardo Spina and Maria Rosaria Muscatello
Affiliation:
Keywords:
Antidepressants, efficacy, levomilnacipran extended release, major depressive disorder, safety, tolerability.
Abstract: Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake
inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive
disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for
once-daily administration, thereby improving patient adherence. This agent differs from other available
SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The
efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials
(one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented
that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm
evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may
be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and
family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse
events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects
included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As
hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to
be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating
efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of
MDD in relation to currently available antidepressants including other SNRIs.
