Clinical data
Trade names Fetzima
  • US: C (Risk not ruled out)
Routes of
By mouth (capsules)
ATC code None
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 92%[1]
Protein binding 22%
Metabolism Hepatic (primarily by CYP3A4)
Biological half-life 12 hours
Excretion Renal
CAS Number 96847-55-1 YesY
175131-60-9 (hydrochloride)
PubChem (CID) 6917779
ChemSpider 5293005 N
KEGG D10072 N
Chemical and physical data
Formula C15H22N2O
Molar mass 246.348 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Levomilnacipran (brand name Fetzima) is an antidepressant approved in the United States for the treatment of major depressive disorder (MDD) in adults.[1] It was developed by Forest Laboratories and Pierre Fabre Group, and was approved by the Food and Drug Administration in July 2013.[2] Levomilnacipran is the levo- enantiomer of milnacipran, and has similar effects and pharmacology, acting as a serotonin-norepinephrine reuptake inhibitor (SNRI).[3][4]

The FDA approved levomilnacipran in July 2013 based on the results of one 10-week phase II and four 8-week phase III clinical trials. Four of the five trials demonstrated a statistically significant superiority to placebo as measured by the Montgomery–Åsberg Depression Rating Scale. Superiority to placebo was also demonstrated by improvement in the Sheehan Disability Scale. Side effects seen more often than with placebo included nausea, dizziness, sweating, constipation, insomnia, increased heart rate and blood pressure, urinary hesitancy, erectile dysfunction and delayed ejaculation in males, vomiting, tachycardia, and palpitations.[2][5]

Relative to other SNRIs, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine.[6][7][8] To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 10:1, milnacipran = 1:1, and levomilnacipran = 1:2.[6] The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear,[6] but may include improved effectiveness, though also increased side effects.[7][8][9]

Levomilnacipran has recently been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for β-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease.[10]


  1. 1 2 "Fetzima (levomilnacipran) Extended-Release Capsules, for Oral Use. Full Prescribing Information". Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045 USA. July 2014. Retrieved 2 September 2016.
  2. 1 2 Citrome L (November 2013). "Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant--what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?". Int. J. Clin. Pract. 67 (11): 1089–104. doi:10.1111/ijcp.12298. PMID 24016209.
  3. "Pierre Fabre Medicament and Forest Laboratories to Collaborate on Development and Commercialization of F2695 for Depression - FierceBiotech".
  4. Deprez D, Chassard D, Baille P, Mignot A, Ung HL, Puozzo C (1998). "Which bioequivalence study for a racemic drug? Application to milnacipran". European Journal of Drug Metabolism and Pharmacokinetics. 23 (2): 166–71. doi:10.1007/bf03189334. PMID 9725476.
  5. Sambunaris A, Bose A, Gommoll CP, Chen C, Greenberg WM, Sheehan DV (February 2014). "A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder". J Clin Psychopharmacol. 34 (1): 47–56. doi:10.1097/JCP.0000000000000060. PMC 4047313Freely accessible. PMID 24172209.
  6. 1 2 3 Sansone RA, Sansone LA (March 2014). "Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison". Innov Clin Neurosci. 11 (3-4): 37–42. PMC 4008300Freely accessible. PMID 24800132.
  7. 1 2 Saraceni MM, Venci JV, Gandhi MA (December 2013). "Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder". J Pharm Pract. 27: 389–395. doi:10.1177/0897190013516504. PMID 24381243.
  8. 1 2 Kasper S, Pail G (2010). "Milnacipran: a unique antidepressant?". Neuropsychiatr Dis Treat. 6: 23–31. doi:10.2147/NDT.S11777. PMC 2938282Freely accessible. PMID 20856597.
  9. Bradley AJ, Lenox-Smith AJ (August 2013). "Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients with depression? A systematic review of meta-analyses and large randomised pragmatic trials". J. Psychopharmacol. (Oxford). 27 (8): 740–58. doi:10.1177/0269881113494937. PMID 23832963.
  10. Rizvi SM, Shaikh S, Khan M, Biswas D, Hameed N, Shakil S (2014). "Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1". CNS Neurol Disord Drug Targets. 13 (8): 1427–31. doi:10.2174/1871527313666141023145703. PMID 25345508.
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