Trazodone

Trazodone is an antidepressant in the serotonin antagonist and reuptake inhibitor (SARI) class. It is approved for major depressive disorder and is commonly used off-label to treat insomnia due to its sedating properties. Brand names include Desyrel and Oleptro, with generic formulations also available.

Mechanism of action involves a combination of pharmacologic effects. Trazodone weakly inhibits serotonin reuptake and strongly antagonizes 5-HT2A and 5-HT2C receptors. It also has antihistamine activity and alpha-1 adrenergic antagonism, which contribute to sedation and blood-pressure effects. The drug is metabolized in the liver, producing active metabolites such as m-chlorophenylpiperazine (m-CPP).

Administration and formulations vary. Trazodone is taken by mouth in immediate-release tablets or as an extended-release formulation. Dosing is individualized and guided by clinical response and tolerability. Typical initial regimens for adults may start around 150 mg per day, with gradual uptitration as needed. The extended-release product is usually given once daily, with a maximum commonly cited around 375 mg per day, depending on the formulation and clinical guidelines.

Side effects and safety considerations are important. Common adverse effects include drowsiness, dizziness, dry mouth, nausea, and constipation, along with potential orthostatic hypotension. Sedation often limits daytime use. Rare but serious risks include priapism and, less commonly, QT prolongation. Serotonergic interactions can lead to serotonin syndrome when combined with other agents; concurrent alcohol or CNS depressants can enhance sedation.

Interactions and cautions. Trazodone is metabolized by CYP3A4, so strong inhibitors or inducers can affect levels. Use with other serotonergic drugs, MAO inhibitors, or significant hepatic impairment requires caution. Pregnancy category C; use during pregnancy or lactation should be discussed with a clinician.

History. Trazodone was developed in the mid-20th century and received FDA approval in 1981, with extended-release formulations introduced later to address tolerability and adherence.