Trazodone (Desyrel)

Route of Administration:
Oral (well absorbed)
Peak blood levels:
1-2 hours after dosing
Protein Binding:
Bioavailability is Not influenced by age or food
7-10 hours
Extensive Hepatic Metabolism: 2D6, 3A4

starting dose:
> IR: 50mg PO TID
> ER: 150mg PO QHS
best time to dose: Morning
how to dose:
> IR: Initial 50mg PO TID for 1 week. Increase by 50mg per day every
week until response (for depression, typically 300mg-400mg per day).
Max dose 600mg/day.
> ER: Initial 150mg PO QHS for 1 week. Increase by 75mg/day every 3 days.
Max dose 375mg/day.
pregnancy: Minimal Safety Data. Consider discontinuing.
breastfeeding: Minimal Safety Data. Consider discontinuing.
FDA Indications:
1) Major Depressive Disorder




  • Trazodone is considered a Serotonin Antagonist and Reuptake Inhibitor (SARI) with the following properties:
    • Antagonist actions at 5HT2A and 5HT2C
    • Weak inhibitor of serotonin transporter (SERT)
    • Partial agonist at 5HT1A receptors
    • Antagonist actions at H1 receptors
    • Antagonist actions at postsynaptic α1 receptors


  • Different doses of Trazodone have different properties:

At low Doses:

  • 5-HT2A receptor antagonist, H1 antagonism, and α1-adrenergic antagonism
  • Minimal SERT or 5-HT2C inhibition properties

At high Doses:

  • 5-HT2A inhibition 
  • 5HT2C inhibition 
  • SERT inhibition


  • Trazodone was never a great antidepressant due to sedation
  • Questionable efficacy for depression at doses <375mg/day.
  • Interestingly, hypnotic effects are not due to anticholinergic and probably not antihistaminergic effects.
  • Trazodone is often used for insomnia.
    • Studies suggest that trazodone increases slow wave sleep with minimal effects on sleep architecture
  • Trazodone is probably a better anxiolytic than antidepressant
  • Trazodone has minimal anticholinergic properties (good for elderly)
  • Trazodone may cause Orthostatic hypotension due to alpha-1 blockade
  • Trazodone increases the risk of priapism (Trazo-BONE).
  • Metabolized primarily through CYP3A4 to active metabolite.
  • Trazodone induces P-glycoprotein
  • Patients taking trazodone may test positive on urine tests for the presence of MDMA or “ecstasy.”


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