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Nortriptyline (Pamelor)

TCA • Last reviewed 2025-09-27

General information

Nortriptyline is a secondary amine tricyclic antidepressant indicated for depression, especially when endogenous features are prominent. Compared with tertiary amine TCAs, nortriptyline has fewer anticholinergic effects and is often preferred in older adults.

Therapeutic drug monitoring improves outcomes: response correlates with plasma levels 50–150 ng/mL. CYP2D6 genotype significantly affects serum concentrations and side-effect risk.

Because TCAs can precipitate arrhythmias, baseline ECG screening is recommended in patients over 40 or with cardiac disease.

Common adverse effects include dry mouth, constipation, blurred vision, and somnolence; patients should be counselled on fall prevention and bowel regimens.

Dosing & administration

Start 25 mg at bedtime; increase by 25 mg every 3–7 days as tolerated.

Typical maintenance 50–150 mg/day (single bedtime dose or divided).

Reduce dose in hepatic impairment or CYP2D6 poor metabolizers.

Mechanism of action

Inhibits norepinephrine reuptake > serotonin reuptake; additional anticholinergic and antihistamine activity contributes to side effects.

Metabolism & pharmacokinetics

Bioavailability ~70%. Peak concentrations 6–8 h post-dose. Extensive hepatic metabolism (CYP2D6) to 10-hydroxynortriptyline; elimination half-life 18–90 h depending on genotype.

Drug interactions

Avoid MAOIs or linezolid within 14 days (serotonin syndrome).

CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) raise levels; adjust dose.

Alcohol/CNS depressants enhance sedation; caution with other QT-prolonging agents.

Monitoring & safety checks

Discontinuation guidance

Taper slowly over ≥4 weeks to minimize cholinergic rebound (GI upset, dizziness).

References

  1. Nortriptyline Prescribing Information — DailyMed
  2. Therapeutic drug monitoring of tricyclic antidepressants — Ther Drug Monit (2022)
  3. CANMAT guidance on secondary amine TCAs (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.