Levomilnacipran
Fetzima
Serotonin-Norepinephrine Reuptake InhibitorGeneric availableTDM data
The exact mechanism of the antidepressant action of levomilnacipran is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of reuptake at serotonin and norepinephrine transporters. Non-clinical studies have shown that levomilnacipran is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI).
Compare Levomilnacipran →FDA-Approved Indications
- Major depressive disorder (adults)
Common Off-Label Uses
- Fibromyalgia
- Neuropathic pain
What Sets This Drug Apart
- Unique among SNRIs: NET-preferring pharmacology (NET:SERT selectivity ~50:1, reversed from all other SNRIs) — may selectively benefit fatigue, anergy, and psychomotor retardation
- More activating than other SNRIs; insomnia and tachycardia risk notably higher; take in morning
- Urinary hesitancy more common than with other SNRIs, particularly in older men; alpha-1 antagonists (tamsulosin) can reverse this
- Gradual titration required: start 20 mg daily, increase by 40 mg increments every 2+ days to max 120 mg
- FDA-approved for MDD only; explicitly NOT approved for fibromyalgia (label states this limitation)
- Minimal CYP inhibition — no significant drug-drug interactions via CYP pathway; CYP3A4 substrate
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS