Trazodone: Uses, Dosage, Side Effects, and What to Expect

Trazodone (brand name: Desyrel, Oleptro) is a serotonin antagonist and reuptake inhibitor (sari). Trazodone has a dual mechanism: it blocks serotonin 5-HT2A receptors and inhibits serotonin reuptake. At low doses (25-100 mg), the 5-HT2A antagonism and histamine H1 antagonism dominate, producing sedation and sleep. At higher antidepressant doses (150-400 mg), serotonin reuptake inhibition becomes significant. Its metabolite mCPP is a 5-HT2C agonist, which may contribute to anxiety early in treatment.

• Major Depressive Disorder

Common off-label uses:

• Insomnia (most common use — prescribed far more often for sleep than for depression)
• Anxiety
• Agitation in dementia
• Nightmares (particularly PTSD-related)

For insomnia: 25-100 mg at bedtime (start at 25-50 mg). For depression: 150-400 mg/day in divided doses (rarely used at these doses). Extended-release (Oleptro): 150-375 mg once daily at bedtime. Take with food to reduce dizziness and improve absorption.

Sedative effects are immediate (first dose). Antidepressant effects at higher doses take 2-6 weeks.

• Sedation and drowsiness
• Dizziness and lightheadedness
• Dry mouth
• Headache
• Nausea
• Blurred vision
• Morning grogginess

• Priapism (prolonged, painful erection — rare but a medical emergency, ~1 in 10,000)
• Orthostatic hypotension (particularly in elderly)
• Cardiac arrhythmias at high doses
• Serotonin syndrome (when combined with other serotonergic drugs)
• Suicidal ideation in young adults (FDA black box warning applies to all antidepressants)

Increases effects of CNS depressants (alcohol, benzodiazepines). CYP3A4 substrate — levels increase with ketoconazole, ritonavir. Caution with other serotonergic drugs. Can increase digoxin and phenytoin levels.

FDA Pregnancy Category C. Limited data. Generally considered lower risk than benzodiazepines for sleep during pregnancy, but discuss with prescriber.

Taper gradually if used chronically. Discontinuation symptoms are generally mild but can include rebound insomnia, anxiety, and irritability.