Trazodone Tapering Guide
trazodone
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.
25mg, 50mg, 100mg, 150mg
Tablets: 50mg, 100mg, 150mg, 300mg; Extended-release tablets (Oleptro): 150mg, 300mg
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
Often prescribed for insomnia at low doses. Rebound insomnia is the most common withdrawal symptom. Tablets can be split.
Hyperbolic Tapering Guidance
When used for sleep at low doses, taper gradually to minimize rebound insomnia. Tablets can be split for small reductions.
Summary written by TaperCommunity, informed by the Maudsley Deprescribing Guidelines (Horowitz & Taylor) and related literature — see Sources & References below. Not affiliated with or endorsed by the Maudsley.
Common Withdrawal Symptoms
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
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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Other Drug Profiles
Sources & References
Trazodone (trazodone) information on this page is sourced from peer-reviewed research, regulatory bodies, clinical guidelines, and patient-advocacy organizations.
Encyclopedic & chemical databases
Neutral, high-authority entity references.
Peer-reviewed research
Primary literature cited in this taper guide.
Clinical guidelines
Evidence-based deprescribing and prescribing standards.
Deprescribing-specific resources
Clinician-facing references on tapering protocols.
- Deprescribing.org — Evidence-based deprescribing algorithms from the Bruyère Research Institute
- Royal College of Psychiatrists — Stopping antidepressants — UK clinical guidance on safely discontinuing antidepressants
Patient-advocacy & lived-experience
Long-running communities documenting withdrawal experience.
- Surviving Antidepressants — tapering forum — Long-running community archive of antidepressant taper experiences
- Inner Compass Initiative — Withdrawal Project — Peer-led resources for psychiatric drug withdrawal
- Mad in America — antidepressant withdrawal archive — Journalism and personal narratives on SSRI/SNRI discontinuation
- RxISK — adverse drug reaction reporting — Independent database of patient-reported adverse effects
TaperCommunity does not provide medical advice. Always consult a qualified prescriber before adjusting psychiatric medication.