Levomilnacipran

Levomilnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) and the single enantiomer of milnacipran. It is approved for the treatment of major depressive disorder in adults and is marketed under the brand name Fetzima in the United States. By blocking the transporters for norepinephrine and serotonin, levomilnacipran increases the synaptic levels of these neurotransmitters, with a relatively greater emphasis on norepinephrine reuptake inhibition.

Pharmacology and pharmacokinetics: Levomilnacipran acts as a dual reuptake inhibitor of norepinephrine and serotonin, with higher potency for the norepinephrine transporter than for the serotonin transporter. It is administered orally and achieves peak plasma concentrations within a few hours. The drug has a half-life that supports once-daily dosing and is primarily metabolized in the liver, with metabolites excreted in urine.

Indications and dosing: The medication is indicated for adults with major depressive disorder. Typical dosing starts at 20 mg once daily, with gradual titration to a target dose in the 40–120 mg per day range, and a maximum recommended daily dose of 120 mg. Dose adjustments may be needed for tolerance, concomitant medications, or hepatic impairment.

Adverse effects and safety: Common adverse effects include nausea, dry mouth, headache, increased heart rate, elevated blood pressure, sweating, and constipation. Sexual dysfunction and insomnia may occur. As with other SNRIs, there is a risk of suicidality in young adults, and blood pressure or heart rate should be monitored during treatment. Serotonergic drugs can interact to increase the risk of serotonin syndrome.

Contraindications and interactions: Levomilnacipran is contraindicated with monoamine oxidase inhibitors and should not be used within a washout period around MAOI therapy. Caution is advised when used with other serotonergic agents or in conditions that heighten cardiovascular risk.