Levomilnacipran

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

Levomilnacipran is an extended-release SNRI approved for major depressive disorder in adults. Compared with many SNRIs it has prominent norepinephrine reuptake inhibition, so blood pressure, heart rate, urinary hesitation, and activation symptoms require attention. It carries the antidepressant boxed warning for suicidal thoughts and behaviors in pediatric and young adult patients.

Exploratory record, not a reviewed medical publication.

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This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

Levomilnacipran is an extended-release SNRI approved for major depressive disorder in adults. NutriStack rates the supporting evidence as strong. Common adult dosing is Start 20 mg once daily for 2 days, then 40 mg once daily. Usual range is 40-120 mg once daily; do not exceed 80 mg once daily with strong CYP3A4 inhibitors., though a prescriber sets the actual dose. This profile indexes 3 sources.

What it's good for

Treatment of major depressive disorder in adults¹
Improvement in depressed mood and low motivation
Once-daily extended-release administration^3,1

What to watch for

Nausea
Constipation
Hyperhidrosis
Hypersensitivity to levomilnacipran, milnacipran, or formulation components^1,3
Concurrent use with an MAOI, linezolid, or intravenous methylene blue³

The bottom line

Evidence rating strong. Most-documented uses: treatment of major depressive disorder in adults, improvement in depressed mood and low motivation, once-daily extended-release administration. 3 sources indexed (2005–2024), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Levomilnacipran inhibits reuptake of norepinephrine and serotonin, increasing monoaminergic signaling in CNS pathways involved in mood and motivation. It has greater norepinephrine than serotonin reuptake inhibition in vitro. It is metabolized partly by CYP3A4 and eliminated substantially by the kidney, so severe renal impairment and strong CYP3A4 inhibitors require dose limits.^1,2

Class

Serotonin-norepinephrine reuptake inhibitor antidepressant

Dosing

Dosing & protocol.

Common range

Start 20 mg once daily for 2 days, then 40 mg once daily. Usual range is 40-120 mg once daily; do not exceed 80 mg once daily with strong CYP3A4 inhibitors.

Recommended form

Extended-release oral capsule swallowed whole once daily

Can be taken with or without food. Capsules should be swallowed whole and not opened, crushed, or chewed.³

Safety

Full safety detail.

Side effects

Nausea
Constipation
Hyperhidrosis
Increased heart rate
Increased blood pressure
Urinary hesitation or retention
Erectile dysfunction or delayed ejaculation
Serotonin syndrome with serotonergic agents
Hyponatremia
Bleeding risk
Activation of mania or hypomania

Contraindications

Hypersensitivity to levomilnacipran, milnacipran, or formulation components^1,3
Concurrent use with an MAOI, linezolid, or intravenous methylene blue³
Do not start levomilnacipran within 14 days after stopping an MAOI^3,1
Do not start an MAOI within 7 days after stopping levomilnacipran³

Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Reviews & position papers

1Levomilnacipran extended release for the treatment of major depressive disorderAsnis GM, D'Arcy J · Drugs of Today · 2015
Review summarizes pharmacology, efficacy, and noradrenergic adverse effects such as increased pulse and blood pressure.
2The serotonin syndromeBoyer EW, Shannon M · New England Journal of Medicine · 2005
The review supports avoiding combinations of serotonergic drugs and supplements that increase serotonin production or signaling.

Reference material

3FETZIMA (levomilnacipran) extended-release capsules, US Prescribing InformationURLAllergan USA Inc. · DailyMed · 2024
Labeling describes MDD indication, titration, dose limits with strong CYP3A4 inhibitors, blood pressure and heart rate warnings, and MAOI contraindications.

FAQ

Common questions.

Quick answers about Levomilnacipran, drawn from the data on this page.

What is Levomilnacipran?

What is Levomilnacipran used for?

Commonly cited benefits of Levomilnacipran include: Treatment of major depressive disorder in adults; Improvement in depressed mood and low motivation; Once-daily extended-release administration. NutriStack rates the overall evidence as strong.

What is a typical dose of Levomilnacipran?

A typical adult dose of Levomilnacipran is Start 20 mg once daily for 2 days, then 40 mg once daily. Usual range is 40-120 mg once daily; do not exceed 80 mg once daily with strong CYP3A4 inhibitors.. The commonly recommended form is Extended-release oral capsule swallowed whole once daily. These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Levomilnacipran?

Reported side effects include nausea, constipation, hyperhidrosis, increased heart rate, increased blood pressure, urinary hesitation or retention. This is educational information; check with a healthcare professional before use.

How strong is the evidence for Levomilnacipran?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

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