The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review.

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Bruno A, Morabito P, Spina E, Muscatello MR

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review.

Curr Neuropharmacol. 2016;14(2):191-9.

PubMed ID

26572745 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drugs

Levomilnacipran

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Levomilnacipran	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate	Details
Levomilnacipran	Cytochrome P450 2C8	Protein	Humans	Unknown	Substrate	Details
Levomilnacipran	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate	Details
Levomilnacipran	Cytochrome P450 2J2	Protein	Humans	Unknown	Substrate	Details

Drug Reactions

Reaction
Levomilnacipran DB08918 Cytochrome P450 3A4 Cytochrome P450 2C8 Cytochrome P450 2C19 Cytochrome P450 2D6 Cytochrome P450 2J2 N-desethyl levomilnacipran DBMET03702	Details
Levomilnacipran DB08918 p-Hydroxy-levomilnacipran DBMET03703	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Levomilnacipran Thalidomide	The metabolism of Levomilnacipran can be increased when combined with Thalidomide.
Levomilnacipran Esketamine	The metabolism of Levomilnacipran can be increased when combined with Esketamine.
Levomilnacipran Mifepristone	The metabolism of Levomilnacipran can be increased when combined with Mifepristone.
Levomilnacipran Lorlatinib	The metabolism of Levomilnacipran can be increased when combined with Lorlatinib.
Levomilnacipran Pegvisomant	The metabolism of Levomilnacipran can be increased when combined with Pegvisomant.