Fetzima Tapering Guide
levomilnacipran
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Levomilnacipran is the more pharmacologically active enantiomer of milnacipran. It is an SNRI approved for major depressive disorder with approximately 2:1 selectivity for norepinephrine over serotonin reuptake inhibition.
20mg, 40mg, 80mg, 120mg
Extended-release capsules: 20mg, 40mg, 80mg, 120mg
Category C (risk cannot be ruled out)
Mechanism of Action
Potent dual reuptake inhibitor of serotonin and norepinephrine with preferential norepinephrine activity (NET > SERT, approximately 2:1 ratio). The active S-enantiomer of milnacipran.
Taper Notes
Active enantiomer of milnacipran with stronger norepinephrine reuptake inhibition. Extended-release formulation allows once-daily dosing. Taper gradually over weeks.
Hyperbolic Tapering Guidance
Reduce dose gradually. Consider stepping down by one dose level (e.g., 120→80→40→20) every 1–2 weeks. Extended-release capsules should not be crushed or opened.
Summary written by TaperCommunity, informed by the Maudsley Deprescribing Guidelines (Horowitz & Taylor) and related literature — see Sources & References below. Not affiliated with or endorsed by the Maudsley.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (risk of serotonin syndrome)
- Strong CYP3A4 inhibitors (ketoconazole) — max dose 80mg/day
- Serotonergic drugs increase serotonin syndrome risk
Food Interactions
- No significant food effect on absorption
- May be taken with or without food
Contraindications
- MAOIs within 14 days
- Uncontrolled narrow-angle glaucoma
- Known hypersensitivity to levomilnacipran or milnacipran
Toxicity
Serotonin syndrome risk. Blood pressure and heart rate increases. Urinary hesitation.
Pharmacokinetics
ADME Profile
Well absorbed, bioavailability ~92%. Tmax ~6–8 hours (extended-release). Food does not affect AUC.
387–473 L
Hepatic via CYP3A4 (major) with minor contribution from CYP2C8, CYP2C19, CYP2D6, and CYP2J2. Desethyl metabolite (inactive).
Renal (58% unchanged).
22%
~21 L/hr
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Other Drug Profiles
Sources & References
Fetzima (levomilnacipran) information on this page is sourced from peer-reviewed research, regulatory bodies, clinical guidelines, and patient-advocacy organizations.
Encyclopedic & chemical databases
Neutral, high-authority entity references.
Peer-reviewed research
Primary literature cited in this taper guide.
- Horowitz MA, Taylor D 2019 — Tapering of SSRI treatment to mitigate withdrawal symptoms (hyperbolic taper) (The Lancet Psychiatry)
- Davies J, Read J 2019 — A systematic review into the incidence, severity and duration of antidepressant withdrawal effects (Addictive Behaviors)
- Framer A 2021 — The patient voice: an exploration of the experience of withdrawal from antidepressants (Therapeutic Advances in Psychopharmacology)
Clinical guidelines
Evidence-based deprescribing and prescribing standards.
Deprescribing-specific resources
Clinician-facing references on tapering protocols.
- Deprescribing.org — Evidence-based deprescribing algorithms from the Bruyère Research Institute
- Royal College of Psychiatrists — Stopping antidepressants — UK clinical guidance on safely discontinuing antidepressants
Patient-advocacy & lived-experience
Long-running communities documenting withdrawal experience.
- Surviving Antidepressants — tapering forum — Long-running community archive of antidepressant taper experiences
- Inner Compass Initiative — Withdrawal Project — Peer-led resources for psychiatric drug withdrawal
- Mad in America — antidepressant withdrawal archive — Journalism and personal narratives on SSRI/SNRI discontinuation
- RxISK — adverse drug reaction reporting — Independent database of patient-reported adverse effects
TaperCommunity does not provide medical advice. Always consult a qualified prescriber before adjusting psychiatric medication.