Silenor / Sinequan Withdrawal & Tapering Guide
doxepin
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial antidepressant treatment.
In short
Silenor / Sinequan (doxepin) is a TCA with a half-life of 15-31 hours (parent); active metabolite nordoxepin 28-81 hours. For low-dose insomnia use, 1-2 week stepdown is usually adequate. Withdrawal symptoms, when they occur, usually begin 1-3 days after dose reduction and settle within 2-4 weeks. It is also sold as Silenor, Sinequan, Adapin.
- Class
- TCA
- Half-life
- 15-31 hours (parent); active metabolite nordoxepin 28-81 hours
- Common doses
- 10mg, 25mg, 50mg, 75mg, 100mg, 150mg capsules; 3mg, 6mg tablets (Silenor for insomnia)
- Withdrawal onset
- 1-3 days after dose reduction
- Typical resolution
- 2-4 weeks
Educational reference only. Dose changes are decided with the prescriber who knows your history.
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
The arithmetic of a proportional reduction
The Maudsley Deprescribing Guidelines and NICE NG222 describe reducing TCA medications by a proportion of the previous dose rather than by a fixed amount, so each cut is smaller than the last. The table shows what that arithmetic produces at 10% per step, using 25 mg only as a worked example. How large each step is, how long it is held, and whether this pattern applies at all are decisions for the person and their prescriber.
| Step | % of starting dose | Worked example (25 mg start) |
|---|---|---|
| Start | 100% | 25 mg |
| Step 1 | 90% | 22.5 mg |
| Step 2 | 81% | 20.3 mg |
| Step 3 | 73% | 18.2 mg |
| Step 4 | 66% | 16.4 mg |
| Step 5 | 59% | 14.8 mg |
| Step 6 | 53% | 13.3 mg |
| Step 7 | 48% | 12 mg |
| Step 8 | 43% | 10.8 mg |
This is an illustration of a published method, not a schedule for anyone. It does not account for how long you have taken Silenor / Sinequan, your current dose, formulation, or history. TaperCommunity does not recommend doses or dose changes; those are agreed with your prescriber.
Frequently asked questions about Silenor / Sinequan
What are the withdrawal symptoms of Silenor / Sinequan (doxepin)?
Common withdrawal symptoms of Silenor / Sinequan (doxepin) include: cholinergic rebound, rebound insomnia, GI upset, flu-like symptoms, anxiety, vivid dreams. Symptom severity varies by individual, dose, and duration of use.
How should I taper off Silenor / Sinequan (doxepin)?
For low-dose insomnia use, 1-2 week stepdown is usually adequate. For antidepressant doses, slow hyperbolic taper. Long-acting metabolite means dose changes take ~2 weeks to fully reflect at steady state — be patient between cuts.
How long does Silenor / Sinequan withdrawal last?
Silenor / Sinequan withdrawal typically begins 1-3 days after dose reduction, peaks around 4-10 days, and resolves within 2-4 weeks. Rebound insomnia can persist 2-6 weeks, especially if used long-term for sleep
Can I stop Silenor / Sinequan cold turkey?
Stopping Silenor / Sinequan abruptly is not recommended. Its half-life is 15-31 hours (parent); active metabolite nordoxepin 28-81 hours, and the receptor adaptations built up during treatment do not reverse at that speed, so a sudden stop tends to produce the sharpest withdrawal. Prescribing guidance favours gradual, proportional reductions agreed with your prescriber.
How long does Silenor / Sinequan stay in your system?
Silenor / Sinequan (doxepin) has a half-life of 15-31 hours (parent); active metabolite nordoxepin 28-81 hours. As a rule of thumb, a drug is mostly cleared after about five half-lives. Withdrawal symptoms often begin before the drug has fully cleared and continue after it has, because the adaptations the brain made during treatment reverse more slowly than the drug leaves the blood.
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.