Milnacipran
Savella
Serotonin-Norepinephrine Reuptake InhibitorGeneric availableTDM data
Milnacipran is a potent inhibitor of neuronal norepinephrine and serotonin reuptake with approximately 3-fold higher potency for NET vs SERT. Does not directly affect dopamine. Exact mechanism in fibromyalgia unknown but presumably enhances central pain inhibition through dual monoamine reuptake inhibition. CRITICAL: FDA-approved ONLY for fibromyalgia, not for depression despite SNRI classification.
Compare Milnacipran →FDA-Approved Indications
- Fibromyalgia in adults ONLY
Common Off-Label Uses
- Depression (approved outside US; not FDA-approved for MDD in US)
- Chronic pain syndromes
- Chronic fatigue syndrome
What Sets This Drug Apart
- CRITICAL: FDA-approved ONLY for fibromyalgia, NOT depression — off-label antidepressant use not FDA-sanctioned despite SNRI classification
- Balanced SERT/NET inhibitor with 3-fold higher potency for norepinephrine — increases sympathetic tone, blood pressure, heart rate
- 55% renal excretion unchanged — requires renal function monitoring; 50% dose reduction if severe RI (CLcr 5-29)
- Minimal CYP450 metabolism — no significant drug interactions with CYP substrates; clean interaction profile vs other SNRIs
- High rate of genitourinary adverse effects in males (dysuria, testicular pain, erectile dysfunction) from noradrenergic effects
- Significant hypertension and tachycardia (5-7%) from net inhibition; requires BP/HR monitoring at baseline and periodically
Boxed Warning
Suicidality risk in children, adolescents, and young adults with MDD and other psychiatric disorders — similar to other SNRIs/SSRIs
Boxed Warning
CRITICAL: Milnacipran is NOT approved for depression