Trazodone (Desyrel)

Trazodone (Tradename: Desyrel) is a Serotonin Antagonist and Reuptake Inhibitor (SARI).

• Trazodone is a close relative of nefazodone (Serzone), a medication that was discontinued due to hepatoxicity.

• At low doses (<150 mg) trazodone has:
  • Serotonin (5-HT) receptor antagonism
    • 5-HT2A (majority)
    • 5-HT2C (minority)
  • Histamine (H1) receptor antagonism
  • Alpha 1 (α1) receptor antagonism
  • The antagonism of 5-HT2A, α1, and H1, causes sedation at any dose. However, trazodone has very weak serotonin reuptake transporter (SERT) or 5-HT2C antagonism properties at low doses. This explains why at low doses, trazodone is ineffective as an antidepressant, but can be used as a non-habit forming sedative, and is also safe to combine with MAOIs
• At high doses (150 to 600 mg per day) trazodone:
  • Actually “becomes an antidepressant” because trazodone basically inhibits 5-HT2A receptors at any dose, but to get an “antidepressant effect,” the dose needs to be much higher to start recruiting SERT inhibition (which increases serotonin levels).
• One of the other unique things about trazodone is it has no sexual dysfunction side effects, this is because antidepressant-induced sexual dysfunction is thought to be due to 5HT2A stimulation (agonism), thus trazodone does the reverse of this.

• Half-life = ~8 to 10 hours
• Tmax = ~60 minutes, delayed to 2.5 hours when taken with food

• 25-600mg (up to 200mg frequently used for sedation)

Extensive CYP450 3A4 metabolism

Main drug interactions extensive CYP450 3A4 metabolism

Contraindications concomitant use with a monoamine oxidase inhibitor (MAOi), IV methylene blue, linezolid may lead to increased risk of serotonin syndrome, concomitant use with saquinavir/ritonavir

Nausea, headache, somnolence, blurred vision, fatigue, prolonged QTc is unlikely^[1], rare seizures, hypotension, dizziness, dry mouth, and sedation.

• Priapism (due to α1 blockade)