Silenor / Sinequan Tapering Guide
doxepin
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial antidepressant treatment.
Overview
Doxepin is a tricyclic antidepressant. At antidepressant doses (75-300mg) it acts on serotonin and norepinephrine. At very low doses (3-6mg, branded Silenor) it acts almost purely as a histamine H1 antagonist for insomnia.
10mg, 25mg, 50mg, 75mg, 100mg, 150mg capsules; 3mg, 6mg tablets (Silenor for insomnia)
Capsules: 10mg, 25mg, 50mg, 75mg, 100mg, 150mg; Tablets (Silenor): 3mg, 6mg; Oral solution: 10mg/mL
Category C
Mechanism of Action
Blocks serotonin and norepinephrine reuptake at high doses; potent histamine H1 antagonism dominates at low doses. Also has muscarinic and alpha-1 effects at antidepressant doses.
Taper Notes
For low-dose insomnia use, 1-2 week stepdown is usually adequate. For antidepressant doses, slow hyperbolic taper.
Hyperbolic Tapering Guidance
Long-acting metabolite means dose changes take ~2 weeks to fully reflect at steady state — be patient between cuts.
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.
Withdrawal Timeline
1-3 days after dose reduction
4-10 days
2-4 weeks
Rebound insomnia can persist 2-6 weeks, especially if used long-term for sleep
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated
- Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) — increase exposure
- CNS depressants — additive sedation
Contraindications
- Recent MAOI use
- Untreated narrow-angle glaucoma
- Severe urinary retention
Toxicity
Toxic in overdose at antidepressant doses — cardiac arrhythmia, seizures, anticholinergic toxicity. Low-dose Silenor much safer in overdose.
Pharmacokinetics
ADME Profile
Hepatic via CYP2D6, CYP2C19, CYP1A2 to active nordoxepin.
Renal, primarily as metabolites.
~80%
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Other Drug Profiles
Sources & References
Silenor / Sinequan (doxepin) 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.
Regulatory sources
Official prescribing information and safety notices.
Peer-reviewed research
Primary literature cited in this taper guide.
- Horowitz MA, Taylor D 2019 — Tapering of SSRI treatment to mitigate withdrawal symptoms (hyperbolic taper) (The Lancet Psychiatry)
- Davies J, Read J 2019 — A systematic review into the incidence, severity and duration of antidepressant withdrawal effects (Addictive Behaviors)
- Framer A 2021 — The patient voice: an exploration of the experience of withdrawal from antidepressants (Therapeutic Advances in Psychopharmacology)
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.