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