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Nefazodone

Serzone

Serotonin Antagonist / Reuptake InhibitorGeneric available

Nefazodone inhibits serotonin reuptake (SERT) combined with postsynaptic 5-HT2A receptor antagonism. Dual mechanism enhances antidepressant and anxiolytic effects while reducing sexual dysfunction and weight gain vs SSRIs. Moderate alpha-1 adrenergic antagonism contributes anxiolytic and sleep-promoting effects but causes hypotension.

Compare Nefazodone

FDA-Approved Indications

  • Major depressive disorder in adults

Common Off-Label Uses

  • PTSD (preliminary efficacy data)
  • Panic disorder (preliminary data)
  • Agitated depression in elderly with early dementia (adjunct with trazodone at bedtime)

What Sets This Drug Apart

  • Dual mechanism (SERT + 5-HT2A antagonism) with lower sexual dysfunction vs SSRIs
  • Alpha-1 antagonism provides sleep benefit but causes orthostatic hypotension
  • CRITICAL: Hepatotoxicity black box — liver failure and death reported
  • Moderate CYP3A4 inhibitor — requires 50% benzodiazepine dose cuts
  • Brand Serzone withdrawn; generic available at lower cost
  • Short t1/2 (2-4h) requires BID dosing; food increases absorption
Boxed Warning
HEPATOTOXICITY: Liver failure, transplant, death reported
Boxed Warning
Suicidality in pediatric and young adult patients