levomilnacipran

Adjunctive therapy

Brands: Fetzima

Last reviewed 2025-12-30

Reviewed by PsychMed Editorial Team.

View details

Quick answers

What is levomilnacipran?
Levomilnacipran (brand Fetzima) is an SNRI indicated for major depressive disorder in adults (label). It is the active enantiomer of milnacipran and is described as having relatively greater norepinephrine reuptake inhibition, which can translate to a more “activating” clinical feel in some patients (mechanism/clinical).
What is Fetzima?
Fetzima is a brand name for levomilnacipran.
What is Fetzima (levomilnacipran) used for?
Label indications include: Major depressive disorder (adults).
What drug class is Fetzima (levomilnacipran)?
Serotonin-norepinephrine reuptake inhibitor (SNRI) with relatively greater norepinephrine reuptake inhibition; extended-release formulation for major depressive disorder.
What strengths does Fetzima (levomilnacipran) come in?
Extended-release capsules 20 mg, 40 mg, 80 mg, 120 mg (swallow whole).

Snapshot

Class: Adjunctive therapy
Common US brands: Fetzima
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-30

Label indications

Major depressive disorder (adults).

View labelExact

Clinical Highlights

Levomilnacipran (brand Fetzima) is an SNRI indicated for major depressive disorder in adults (label). It is the active enantiomer of milnacipran and is described as having relatively greater norepinephrine reuptake inhibition, which can translate to a more “activating” clinical feel in some patients (mechanism/clinical). Clinically important adverse-effect themes include nausea, increased heart rate and blood pressure, sweating, and urinary hesitation or retention—topics that often guide selection when anxiety, insomnia, or baseline urinary obstruction risk is present (label/clinical).

Because elimination is predominantly renal and a substantial fraction is excreted unchanged in urine, dose adjustments are needed in renal impairment (label).
The compare view, levomilnacipran evidence feed, and levomilnacipran print page support side-by-side review of activation, blood pressure effects, and discontinuation planning across SNRIs.
As with other antidepressants, screening for bipolar-spectrum history is commonly emphasized because mood switching can occur (clinical).

Dosing & Formulations

Extended-release capsules (label): 20 mg, 40 mg, 80 mg, 120 mg. Label initiation: 20 mg once daily for 2 days, then 40 mg once daily. The recommended dose range is 40–120 mg once daily (label).

Renal impairment requires dose caps (e.g., maximum 80 mg/day in moderate impairment and 40 mg/day in severe impairment in labeling) (label).
Discontinuation symptoms can occur; tapering is commonly used when stopping after longer courses (label/clinical).

Monitoring & Risks

Boxed warning: antidepressants increase risk of suicidal thoughts and behaviors in children, adolescents, and young adults; close monitoring early in treatment is typical (label). Blood pressure and heart rate elevations can occur; monitoring is commonly emphasized at baseline and after dose increases (label).

Urinary hesitation/retention is a labeled risk; this is a key safety screen in patients with prostatic hypertrophy or other obstructive disorders (label/clinical).
Insomnia or activation can occur; dose timing and slower titration are common adjustment levers when anxiety or sleep disruption emerges (clinical).
Serotonin syndrome risk exists with serotonergic combinations (label/class).

Drug Interactions

MAOIs are contraindicated; washout periods are used to reduce risk of serotonin syndrome and severe reactions (label). Strong CYP3A4 inhibitors can increase levomilnacipran exposure; dosing and tolerability are often reassessed when potent inhibitors are started or stopped (label/clinical).

Additive serotonergic burden with SSRIs/SNRIs, linezolid, triptans, and tramadol increases serotonin syndrome risk (label/class).
Agents that raise blood pressure or heart rate (stimulants, decongestants) can compound autonomic effects; medication reconciliation typically includes OTC products (clinical).

Practice Notes

Levomilnacipran is generally used after SSRI nonresponse, similar to other SNRIs; selection often hinges on activation profile, blood pressure tolerance, and renal function (clinical). When depressive symptoms occur in bipolar disorder, antidepressants are commonly paired with a mood stabilizer and monitored for Mania/Hypomania; see the bipolar disorder hub for longitudinal care pathways.

If urinary retention or problematic blood pressure elevation emerges, clinicians commonly reassess alternatives rather than pushing dose increases (clinical).
For discontinuation symptoms, slower taper steps over longer intervals are often better tolerated than larger dose drops (clinical).

References

Fetzima (levomilnacipran) Extended Release Capsules Prescribing Information — DailyMed (2025)
CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)