Trazodone

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) — it blocks certain serotonin receptors (5-HT2A) while also inhibiting serotonin reuptake, producing a net antidepressant and sedative effect. Its sedating properties come primarily from antagonism of histamine H1 receptors and alpha-1 adrenergic receptors, both of which promote drowsiness. Unlike many sedating medications, trazodone does not significantly suppress REM sleep at typical doses, which is why sleep quality is generally preserved.¹

At doses used for sleep (25–100 mg), trazodone primarily produces sedation. At doses used for depression (150–400 mg), the full antidepressant effects emerge.

Major depressive disorder (MDD) — trazodone is FDA-approved as an antidepressant. Its use as a sleep aid is off-label but extremely widespread in clinical practice.¹

For depression: 150 mg per day in divided doses initially, increasing by 50 mg every 3–4 days. Maximum: 400 mg per day (outpatients) or 600 mg per day (inpatients).

For sleep (off-label): 25–150 mg taken 30 minutes before bedtime. Most patients respond to 50–100 mg. The sedating effect occurs at doses lower than those needed for antidepressant effect.¹

Oral tablets (immediate-release). An extended-release formulation (Oleptro) is also available.

Store at controlled room temperature, away from heat and moisture.¹

Key considerations from the FDA label and clinical context:¹

• Serotonin syndrome: Trazodone has serotonergic activity and can contribute to serotonin syndrome when combined with other serotonergic agents — SSRIs, SNRIs, MAOIs, buspirone, triptans, tramadol, and methylene blue. The risk is lower than with SSRIs alone but is not zero.
• Priapism: Trazodone can cause prolonged, painful erections (priapism) in males — a rare but serious adverse effect requiring immediate medical attention. Men who experience sustained or frequent abnormal erections should stop trazodone and seek medical evaluation.
• Orthostatic hypotension: Can cause blood pressure to drop when standing up, particularly at higher doses — risk of dizziness and falls, especially in older adults.
• QT prolongation: Trazodone can prolong the QT interval; avoid combining with other QT-prolonging drugs.
• Sedation: The sedating effect is the most common effect and the reason it is so widely used off-label for sleep. This also means driving and operating machinery should be avoided until individual response is known.
• Taking with food: Taking trazodone shortly after a meal may reduce the incidence of dizziness and lightheadedness.
• Antidepressant warnings: Like all antidepressants, trazodone carries the class boxed warning regarding increased risk of suicidal thoughts and behavior in children, adolescents, and young adults (under 25) during the initial months of treatment.