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Nefazodone ball-and-stick model.png
Clinical data
AHFS/ Monograph
MedlinePlus a695005
  • C
Routes of
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 20% (variable)
Protein binding >99%
Metabolism Hepatic (active metabolites, including mCPP)[1]
Biological half-life 2–4 hours
Excretion Urine (55%), Feces (20–30%)
CAS Number
PubChem CID
Chemical and physical data
Formula C25H32ClN5O2
Molar mass 470.01 g/mol
3D model (Jmol)

Nefazodone is an antidepressant that was first marketed by Bristol-Myers Squibb in 1994.[2] BMS withdrew it from the market by 2004 due to decreasing sales due to the rare incidence of severe liver damage and the onset of generic competition. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years.[3] Generic versions were introduced in 2003.[4]

Medical use[edit]

Nefazodone is used to treat major depressive disorder, aggressive behavior and panic disorder.[5]


Nefazodone is a potent inhibitor of CYP3A4, and may interact adversely with many commonly used medications that are metabolized by CYP3A4.[1][6]

Side effects[edit]

Nefazodone can cause severe liver damage leading to a need for liver transplant and death. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years.[2][3]

Common and mild side effects of nefazodone reported in clinical trials more often than placebo include dry mouth (25%), sleepiness (25%), nausea (22%), dizziness (17%), blurred vision (16%), weakness (11%), lightheadedness (10%), confusion (7%), and orthostatic hypotension (5%). Rare and serious adverse reactions may include allergic reactions, fainting, painful/prolonged erection, and jaundice.[3]

Nefazodone is not especially associated with increased appetite and weight gain.[7]


Nefazodone acts primarily as a potent antagonist at the 5-HT2A receptors (Kd 26 nM).[8] It also has moderate affinity for the α1-adrenergic receptor (Kd 48 nM) and 5-HT1A receptor (Kd 80 nM), and very low affinity for the α2-adrenergic receptor (Kd 640 nM) and D2 receptor (Kd 910 nM).[8] Nefazodone has low affinity for the serotonin (200 nM), norepinephrine (360 nM), and dopamine (360 nM) transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).[9] It has negligible affinity for the H1 receptor (24,000 nM) or muscarinic acetylcholine receptors (11,000 nM), and accordingly lacks any antihistamine or anticholinergic side effects.[9]


Nefazodone is a phenylpiperazine;[10] it is an alpha-phenoxyl derivative of etoperidone which in turn was a derivative of trazodone.[11]


Nefazodone was discovered by scientists at Bristol-Myers Squibb (BMS) who were seeking to improve on trazodone by reducing its sedating qualities.[11]

BMS obtained marketing approvals worldwide for nefazodone in 1994.[2] It was marketed in the US under the brand name Serzone[12] and in Europe under the brand name Dutonin.[13]

In 2002 the FDA obligated BMS to add a black box warning about potential fatal liver toxicity to the drug label.[14][15] Worldwide sales in 2002 were $409 million.[13]

In 2003 Public Citizen filed a citizen petition asking the FDA to withdraw the marketing authorization in the US, and in early 2004 the organization sued the FDA to attempt to force withdrawal of the drug.[14] [16] The FDA issued a response to the petition in June 2004 and filed a motion to dismiss, and Public Citizen withdrew the suit.[16]

Generic versions were introduced in the US in 2003[4] and Health Canada withdrew the marketing authorization that year.[17]

Sales of nefazodone were about $100 million in 2003.[18] By that time it was also being marketed under the additional brand names Serzonil, Nefadar, and Rulivan.[2]

In April 2004, BMS announced that it was going discontinue the sale of Serzone in the US in June 2004 and said that this was due to declining sales.[15][18] By that time BMS had already withdrawn the drug from the market in Europe, Australia, New Zealand and Canada.[15]

As of 2012 generic nefazodone was available in the US.[19]

Society and culture[edit]


As of 2017 it was sold only under its generic name.[20]


The use of nefazodone to prevent migraine has been studied, due to its antagonistic effects on the 5-HT2A[21] and 5-HT2C receptors.[22][23]

See also[edit]


  1. ^ a b Lexi-Comp (September 2008). "Nefazodone". The Merck Manual Professional.  Retrieved on November 29, 2008.
  2. ^ a b c d "Drugs of Current Interest: Nefazodone". WHO Pharmaceuticals Newsletter (1). 2003. 
  3. ^ a b c "Serzone (Nefazodone): Side Effects, Interactions, Warning, Dosage & Uses". RxList. January 2005. Retrieved 3 June 2017. 
  4. ^ a b "Nefazodone". Drug Patent Watch. Retrieved 3 June 2017. 
  5. ^ "Nefazodone". LiverTox (NIDDK). 2 June 2017. 
  6. ^ Spina E, Santoro V, D'Arrigo C (July 2008). "Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update". Clin Ther. 30 (7): 1206–27. PMID 18691982. doi:10.1016/S0149-2918(08)80047-1. 
  7. ^ Sussman N, Ginsberg DL, Bikoff J (April 2001). "Effects of nefazodone on body weight: a pooled analysis of selective serotonin reuptake inhibitor- and imipramine-controlled trials". The Journal of Clinical Psychiatry. 62 (4): 256–60. PMID 11379839. doi:10.4088/JCP.v62n0407. 
  8. ^ a b Cusack B, Nelson A, Richelson E (1994). "Binding of Antidepressants to Human Brain Receptors: Focus on Newer Generation Compounds.". Psychopharmacology (Berl). 114 (4): 559–565. PMID 7855217. doi:10.1007/BF02244985. 
  9. ^ a b Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological Profile of Antidepressants and Related Compounds at Human Monoamine Transporters.". Eur J Pharmacol. 340 (2–3): 249–258. PMID 9537821. doi:10.1016/S0014-2999(97)01393-9. 
  10. ^ Davis, Rick; Whittington, Ruth; Bryson, Harriet M. (April 1997). "Nefazodone". Drugs. 53 (4): 608–636. PMID 9098663. doi:10.2165/00003495-199753040-00006. 
  11. ^ a b Eison, Michael S.; Taylor, Duncan B.; Riblet, Leslie A. (1987). "Atypical Psychotropic Agents". In Williams, Michael; Malick, Jeffrey B. Drug Discovery and Development. Springer Science & Business Media. p. 390. ISBN 9781461248286. 
  12. ^ Associated Press (16 March 2004). "Consumer group seeks ban on antidepressant". NBC News. 
  13. ^ a b Hoffmann, Candace (January 8, 2003). "Bristol-Myers to withdraw Dutonin in Europe". First Word Pharma. 
  14. ^ a b "Public Citizen to sue FDA over Serzone - Pharmaceutical industry news". The Pharma Letter. 22 March 2004. 
  15. ^ a b c Cosgrove-Mather, Bootie (April 15, 2004). "Anti-Depressant Taken Off Market". CBS News. 
  16. ^ a b "Court Decisions and Updates" (PDF). FDA. Retrieved 3 June 2017. 
  17. ^ Lexchin, J (15 March 2005). "Drug withdrawals from the Canadian market for safety reasons, 1963-2004.". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 172 (6): 765–7. PMC 552890Freely accessible. PMID 15767610. 
  18. ^ a b DeNoon, Daniel J. (May 4, 2004). "Company Pulls Antidepressant Off Market". WebMD. 
  19. ^ Sadock, Benjamin J.; Sadock, Virginia A.; Sussman, Norman (2012). "22. Nefazodone". Kaplan & Sadock's Pocket Handbook of Psychiatric Drug Treatment. Lippincott Williams & Wilkins. p. 251. ISBN 9781451154467. 
  20. ^ "Nefazodone International Brands". Retrieved 1 June 2017. 
  21. ^ Saper JR, Lake AE, Tepper SJ (May 2001). "Nefazodone for chronic daily headache prophylaxis: an open-label study". Headache. 41 (5): 465–74. PMID 11380644. doi:10.1046/j.1526-4610.2001.01084.x. 
  22. ^ Mylecharane EJ (1991). "5-HT2 receptor antagonists and migraine therapy". J. Neurol. 238 (Suppl 1): S45–52. PMID 2045831. doi:10.1007/BF01642906. 
  23. ^ Millan MJ (2005). "Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies". Therapie. 60 (5): 441–60. PMID 16433010. doi:10.2515/therapie:2005065.