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Nortriptyline (off-label tobacco cessation context)

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDDRUG-NORTRIPTYLINE-CESSATION
TypeDrug
Aliases
NortrilenNortriptyline (tobacco cessation)PamelorTCA cessation — nortriptylineНортриптилін (off-label — припинення куріння)
Statusreviewed 2026-05-18 | pending_clinical_signoff
DiseasesNone declared
SourcesSRC-NCCN-BCELL-2025

Drug Facts

ClassTricyclic antidepressant (TCA) — secondary amine; off-label tobacco-cessation use
MechanismSecondary-amine tricyclic antidepressant; primary action is inhibition of norepinephrine reuptake (modest serotonin reuptake inhibition), with antagonism at histamine H1, muscarinic, and α1-adrenergic receptors. Mechanism in tobacco cessation is not fully established — proposed contributions include noradrenergic modulation of nicotine withdrawal, anxiety/depressive-symptom mitigation during quit attempts, and direct effect on smoking-related dopaminergic circuits. Cochrane meta-analysis (Hughes 2014 update) — nortriptyline approximately doubles long-term cessation rates vs placebo (RR ~2.0), comparable to bupropion and NRT; LESS evidence and LOWER tolerability than varenicline (DRUG-VARENICLINE — first-line per USPSTF 2021). OFF-LABEL use; second / third-line option for cessation when varenicline / bupropion / NRT have failed or are contraindicated.
Typical dosingTobacco cessation (off-label, Cochrane / NICE): Start 25 mg PO at bedtime × 3 days; titrate upward over 1-2 weeks to target dose of 75-100 mg/day (single bedtime dose or divided BID). Begin ≥10-14 days before target quit date (steady-state + symptom- control window). Total course 8-12 weeks; extend to 6 months if successful. Therapeutic plasma level 50-150 ng/mL (TDM available; consider in CYP2D6 poor / ultra-rapid metabolizers or elderly). Elderly: start 10 mg, max 50-75 mg/day. Hepatic impairment: reduce dose. Renal: no significant adjustment.
Ukraine registeredTrue
NSZU reimbursedFalse
Ukraine last verified2026-05-18

Warnings

Notes

STUB — v0.2 prevention-workstream authoring (batch 3); pending two- Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode. OFF-LABEL tobacco- cessation agent — supported by Cochrane meta-analysis (Hughes 2014) RR ~2.0 vs placebo, similar to bupropion and NRT. SECOND / THIRD-LINE position: USPSTF 2021 / AHCPR / Cochrane place varenicline first (DRUG-VARENICLINE), then NRT + bupropion (DRUG-BUPROPION-SR); TCAs are alternative when first-line have failed or are contraindicated. Particular candidates: depressive comorbidity without contraindication to TCA, neuropathic pain comorbidity (synergy), patients who cannot tolerate varenicline (nausea, vivid dreams) or bupropion (insomnia, seizure-threshold concerns). KEY EXCLUSIONS: cardiac disease (recent MI, conduction defect, prolonged QTc), elderly with high anticholinergic burden, patients on tamoxifen (CYP2D6 effects). Plasma-level monitoring recommended; narrow therapeutic index. Source cited (SRC-NCCN-BCELL- 2025) is closest in-KB until USPSTF/AHCPR/Cochrane tobacco-cessation sources land in source-stub workstream.

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