Trazodone (Desyrel)


Clinical Information

ROUTE OF ADMINISTRATION: Oral (well absorbed)

PEAK BLOOD LEVELS: 1-2 hours after dosing


HALF-LIFE: 7-10 hours

METABOLISM: Liver. CYP2D6 and CYP3A4. Metabolized to an active metabolite. Trazodone induces P-glycoprotein.

STARTING DOSE: 50mg-100mg 


HOW TO DOSE: Initial 50mg-100mg at bedtime for 4-7 days then increase by 50mg-100mg every day until response occurs (for depression, typically 300mg-400mg per day). Max dose 600mg/day.

PREGNANCY: Minimal Safety Data. Consider discontinuing.

BREASTFEEDING: Minimal Safety Data. Consider discontinuing.

Side Effects

Priapism, orthostatic hypotension, drowsiness, fatigue, dizziness, dry mouth, nausea, acid reflux, upset stomach, headaches, restlessness

FDA Indications

  1. Major Depressive Disorder

Off Label Uses: Insomnia, Anxiety

Mechanism(s) of Action

Trazodone is considered a Serotonin Antagonist and Reuptake Inhibitor (SARI) with the following properties:

  • Antagonist actions at 5HT2A and 5HT2C receptors
  • 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, there is prominent 5-HT2A receptor antagonist, H1 antagonism, and α1-adrenergic antagonism and minimal SERT or 5-HT2C inhibition properties. At higher doses, there is increasing 5-HT2A inhibition , 5HT2C inhibition , and SERT inhibition. Trazodone was never a great antidepressant due to sedation. Trazodone has minimal anticholinergic properties (good for elderly). Trazodone may cause Orthostatic hypotension due to alpha-1 blockade. Hypnotic effects are not due to anticholinergic activity or antihistaminergic activity. 

Additional Information

  • Studies suggest that trazodone increases slow wave sleep with minimal effects on sleep architecture
  • Trazodone is probably a better anxiolytic than antidepressant
  • Patients taking trazodone may test positive on urine tests for the presence of MDMA or “ecstasy.”


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