Levomilnacipran
SNRIs
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
The active enantiomer of milnacipran: an SNRI for depression, excreted largely unchanged in urine. It can raise heart rate and cause sweating.
Quick facts
- Group
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- Target
- Serotonin (SERT) and noradrenaline (NET) transporters; NET shown
- Used for
- Major depressive disorder in adults
- Key effects
- Nausea · Excessive sweating · Fast heart rate
- Monitor
- Mood and suicidal thoughts · Urinary symptoms
- ATC
- N06AX28
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows the human noradrenaline transporter solved in the presence of levomilnacipran, with the milnacipran ligand in its central site.
Levomilnacipran is the active enantiomer of milnacipran. It blocks both the serotonin and noradrenaline transporters in a fairly balanced way, so more of both monoamines stays in the synapse; mood improves over weeks. The noradrenergic part explains sweating, fast heart rate and difficulty urinating.
- Levomilnacipran blocks SERT and NET
- More serotonin and noradrenaline in the synapse
- Mood improves over weeks
- Noradrenaline effects: sweating, fast pulse, urinary hesitancy
Indications
- Major depressive disorder in adults Major depressive disorder →
Adverse effects
Common
- Nausea, vomiting, constipation
- Excessive sweating
- Fast heart rate
- Sexual dysfunction and erectile or ejaculation problems
Contraindications
- MAO inhibitors, including linezolid and intravenous methylene blue, now or within the previous two weeks
- Starting an MAO inhibitor less than a week after stopping levomilnacipran
Key interactions
- MAO inhibitors, linezolid, methylene blue, St John's wort, tryptophan
- Serotonin syndrome
- Aspirin and NSAIDs
- More bleeding
- Alcohol
- Worse side effects
What is monitored
- Mood and suicidal thoughts
- Heart rate and blood pressure
- Urinary symptoms
- Sodium in older people
Administration and safety
- The extended-release capsule is swallowed whole, not opened, chewed or crushed
- Not stopped without the treating team, who plan any change
Pregnancy and breastfeeding
Human data are limited; use weighs benefit and risk.
Nursing care
- Records heart rate and blood pressure
- Asks about difficulty urinating, sweating and sexual side effects
- Teaches the patient and family to report suicidal thoughts, agitation or eye pain with halos
- Checks the list for MAO inhibitors, linezolid and NSAIDs
Pharmacokinetics
- Absorption
- Well absorbed by mouth; extended-release capsule
- Metabolism
- Partly desethylated by CYP3A4
- Elimination
- Largely unchanged in urine, so kidney function matters
Test yourself
Think of the answer, then tap the question to see it.
What is the relationship between levomilnacipran and milnacipran?
Levomilnacipran is the active enantiomer of milnacipran.
Which transporters does levomilnacipran block?
Both the serotonin (SERT) and noradrenaline (NET) transporters.
Why is kidney function relevant for levomilnacipran?
It is excreted largely unchanged in the urine.
Connections
← Back to the class: Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Levomilnacipran: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.