TaperCommunitytrazodone
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) approved for major depressive disorder. At antidepressant doses (150–600mg), it modulates serotonin; at lower doses (25–100mg), its potent H1 and 5-HT2A antagonism provides sedation, making it one of the most commonly prescribed sleep aids.
25mg, 50mg, 100mg, 150mg
Tablets: 50mg, 100mg, 150mg, 300mg; Extended-release tablets (Oleptro): 150mg, 300mg
Category C (risk cannot be ruled out)
Serotonin antagonist and reuptake inhibitor (SARI). Blocks 5-HT2A receptors, weakly inhibits serotonin reuptake, and antagonizes histamine H1 and alpha-1 adrenergic receptors. The active metabolite mCPP is a 5-HT2C agonist. At low doses, H1 and 5-HT2A antagonism predominate.
Often prescribed for insomnia at low doses. Rebound insomnia is the most common withdrawal symptom. Tablets can be split.
When used for sleep at low doses, taper gradually to minimize rebound insomnia. Tablets can be split for small reductions.
Toxicity
Priapism (rare but serious — requires immediate medical attention). Orthostatic hypotension. QT prolongation at high doses or in overdose. Serotonin syndrome with serotonergic combinations. Relatively low toxicity in overdose compared to TCAs.
Pharmacokinetics
Well absorbed after oral administration. Bioavailability ~65–80%. Tmax ~1 hour (fasting), ~2 hours (with food). Food increases Cmax and AUC; take shortly after meals.
~0.8–1.5 L/kg
Hepatic via CYP3A4 (primary) to the active metabolite meta-chlorophenylpiperazine (mCPP). Further metabolism produces inactive conjugated metabolites.
Renal (~70–75% as metabolites) and fecal (~21%). Less than 1% excreted unchanged.
~89–95%
~110–230 mL/min (apparent oral clearance)
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