Nortriptyline Tapering Guide
nortriptyline
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Nortriptyline is a secondary amine tricyclic antidepressant and the active metabolite of amitriptyline. It is used for major depressive disorder and off-label for neuropathic pain, migraine prophylaxis, and smoking cessation. It is better tolerated than amitriptyline with fewer anticholinergic and sedative effects.
10mg, 25mg, 50mg, 75mg
Capsules: 10mg, 25mg, 50mg, 75mg; Oral solution: 10mg/5mL
Category D (positive evidence of risk)
Mechanism of Action
Primarily inhibits norepinephrine reuptake, with lesser serotonin reuptake inhibition. Has less anticholinergic, antihistaminic, and alpha-adrenergic blocking activity compared to tertiary amine TCAs like amitriptyline.
Taper Notes
Available in capsule and liquid forms. Less anticholinergic than amitriptyline.
Hyperbolic Tapering Guidance
Oral solution (10mg/5mL) available for gradual reductions. Less sedating than amitriptyline, withdrawal may be milder.
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 (hypertensive crisis and serotonin syndrome)
- CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) significantly increase nortriptyline levels
- QT-prolonging drugs increase arrhythmia risk
Food Interactions
- Food does not significantly affect absorption
- Avoid alcohol (additive CNS depression)
- Grapefruit juice may modestly increase levels
Contraindications
- MAOIs within 14 days
- Acute recovery period post-myocardial infarction
- Known hypersensitivity to nortriptyline
Toxicity
Cardiotoxic in overdose (QRS widening, arrhythmias), though less toxic than amitriptyline. Therapeutic drug monitoring recommended (therapeutic window 50–150 ng/mL).
Pharmacokinetics
ADME Profile
Well absorbed after oral administration. Bioavailability ~46–70%. Tmax 3–12 hours. Food does not significantly affect absorption.
~21 L/kg
Hepatic via CYP2D6 (primary) to 10-hydroxynortriptyline and other hydroxylated metabolites. Also metabolized by CYP2C19 and CYP3A4.
Renal (~40% as metabolites) with ~2% unchanged in urine. Fecal excretion minor.
~93–95%
~500 mL/min (apparent oral clearance, highly variable depending on CYP2D6 status)
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Other Drug Profiles
Sources & References
Nortriptyline (nortriptyline) 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.
- 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.