What are the withdrawal symptoms of Trazodone (trazodone)?

Common withdrawal symptoms of Trazodone (trazodone) include: rebound insomnia, anxiety, irritability, nausea. Symptom severity varies by individual, dose, and duration of use.

How should I taper off Trazodone (trazodone)?

Predominantly prescribed off-label for insomnia at low doses (25–100 mg), where H1 and 5-HT2A antagonism dominate. Rebound histaminergic insomnia is the principal withdrawal feature. Tablets can be split for graduated reductions. For low-dose sleep indication, taper gradually to minimize rebound insomnia. Tablet splitting and aqueous titration support small reductions. Counsel that rebound insomnia is mechanistic (H1 unmasking) rather than primary insomnia recurrence.

Trazodone Tapering Guide

trazodone

OtherFDA 1981

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Boxed Warning

Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.

Overview

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.

Common Doses

25mg, 50mg, 100mg, 150mg

Formulations

Tablets: 50mg, 100mg, 150mg, 300mg; Extended-release tablets (Oleptro): 150mg, 300mg

Pregnancy

Category C (risk cannot be ruled out)

Mechanism of Action

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.

Taper Notes

Predominantly prescribed off-label for insomnia at low doses (25–100 mg), where H1 and 5-HT2A antagonism dominate. Rebound histaminergic insomnia is the principal withdrawal feature. Tablets can be split for graduated reductions.

Maudsley Deprescribing Guidance

For low-dose sleep indication, taper gradually to minimize rebound insomnia. Tablet splitting and aqueous titration support small reductions. Counsel that rebound insomnia is mechanistic (H1 unmasking) rather than primary insomnia recurrence.

Common Withdrawal Symptoms

rebound insomniaanxietyirritabilitynausea

Interactions & Safety

Drug Interactions

MAOIs — contraindicated (serotonin syndrome risk)
CYP3A4 inhibitors (ketoconazole, ritonavir) increase trazodone levels — consider dose reduction
CYP3A4 inducers (carbamazepine) decrease trazodone levels

Food Interactions

Food increases absorption; take shortly after a meal or snack
Avoid alcohol (additive CNS depression)

Contraindications

MAOIs within 14 days
Known hypersensitivity to trazodone

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

ADME Profile

Absorption

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.

Distribution

~0.8–1.5 L/kg

Metabolism

Hepatic via CYP3A4 (primary) to the active metabolite meta-chlorophenylpiperazine (mCPP). Further metabolism produces inactive conjugated metabolites.

Elimination

Renal (~70–75% as metabolites) and fecal (~21%). Less than 1% excreted unchanged.

Protein Binding

~89–95%

Clearance

~110–230 mL/min (apparent oral clearance)

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