Trazadone

Summary

Trazodone is an antagonist or blocker of serotonin, H1, and alpha-1 adrenergic receptors. Trazodone can be used to treat major depressive disorder by modulating serotonin signaling in the brain. It can also be used off-label to treat insomnia due to its strong sedative effects. A major adverse effect of trazodone use is priapism, which is a painful erection lasting more than four hours independent of sexual arousal. Trazodone can also cause hypotension, serotonin syndrome, and nausea.

Key Points

• Trazodone
  • Mechanism:
    • Blocks 5-HT2 receptors
      • Modulates but generally antagonizes 5-HT2 serotonin receptors
      • Also weakly inhibits serotonin reuptake
    • Blocks H1 receptors
      • Accounts for sedative use in treating insomnia
    • Blocks α1-adrenergic receptors
  • Indications
    • Treats Major Depressive Disorder
      • Used to treat depression in patients with insomnia
      • Usually high doses of trazodone are required to treat major depressive disorder.
  • Adverse effects
    • Causes Sedation (can help treat insomnia)
      • Often used off-label to treat insomnia for its strong sedative effects
    • Causes Priapism
      • Priapism refers to an erection lasting more than four hours independent of sexual arousal. Priapism is a dangerous condition because if left untreated it can lead to penile ischemia.  
    • Causes Postural Hypotension
      • Due to blockade of  α1-adrenergic receptors
    • Causes Serotonin Syndrome
      • Especially when used with other serotonin-modulating drugs (SSRIs, SNRIs, MAOIs, TCA’s, etc.)
    • Causes Nausea