THERAPEUTICS

Brands

• Levomilnacipran: Fetzima

Generic?

• No

Class

• Serotonin and norepinephrine reuptake inhibitor (SNRI)

Commonly Prescribed for

(FDA approved in bold)

• Major depressive disorder

• Fibromyalgia

• Post-stroke depression

• Migraine prophylaxis

• Stress urinary incontinence

How the Drug Works

• Both milnacipran and levomilnacipran (levo-enantiomer of milnacipran) are potent balanced inhibitors of serotonin and norepinephrine reuptake transporters (SERT, NET), increasing serotonin and norepinephrine levels within hours, but antidepressant effects take weeks. Effect is more likely related to adaptive changes in serotonin and norepinephrine receptor systems over time

• No affinity for serotonergic, adrenergic, muscarinic, dopamine, opiate, GABA receptors, and Ca2+, Na+, K+, Cl— channels

• It may modulate NMDA receptors in the superficial dorsal horn for antinociceptive effect

• Unlike venlafaxine or duloxetine where SERT effect dominates, milnacipran exerts a relatively equal influence on SERT and NET whereas levomilnacipran demonstrates a slightly greater NET inhibition than SERT inhibition

How Long Until It Works

• 2 weeks to 2 months for full effect

If It Works

• Continue to use and monitor for AEs

If It Doesn't Work

• Increase to highest tolerated dose. Consider adding a second agent or changing to another one

Best Augmenting Combos for Partial Response or Treatment-Resistance

• For some patients, low-dose polytherapy with 2 or more drugs may be better tolerated and more effective than high-dose monotherapy

Tests

• Check blood pressure, at baseline and when increasing dose

• Monitor sodium, intraocular pressure, suicidality, and unusual change in behavior

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• By increasing serotonin and norepinephrine on non-therapeutic responsive receptors throughout the body. Most AEs are doseand time-dependent

Notable AEs

• Incidence ≥ 5%: nausea, vomiting, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, elevated blood pressure, palpitation, urinary hesitancy/retention, and erectile dysfunction

Life-Threatening or Dangerous AEs

• Serotonin syndrome

• Rare hepatotoxicity

• Rare activation of mania/hypomania or suicidal ideation