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Amitriptyline (Elavil)

TCA • Last reviewed 2025-09-27

General information

Amitriptyline is a tertiary amine TCA indicated for depression but frequently used off-label for neuropathic pain and migraine prophylaxis. Strong antihistamine and anticholinergic effects drive sedation and weight gain.

Metabolism to nortriptyline provides additional noradrenergic effect. Combined plasma levels (amitriptyline + nortriptyline) should remain between 80–200 ng/mL to balance response and toxicity.

Cardiac conduction changes (QT prolongation, bundle branch block) and anticholinergic delirium are key safety considerations.

Elderly patients are particularly susceptible to orthostatic hypotension and cognitive impairment; consider lower starting doses and slow titration.

Dosing & administration

Start 25–50 mg at bedtime; increase by 25–50 mg every 3–7 days.

Typical antidepressant target 100–150 mg/day; max 300 mg/day inpatient.

Lower doses (10–75 mg) used for pain/migraine with slower titration.

Mechanism of action

Inhibits serotonin and norepinephrine reuptake; potent H1, muscarinic, and α1 antagonist leading to sedation, dry mouth, and orthostasis.

Metabolism & pharmacokinetics

Peak concentration 4–6 h post-dose. Half-life 21–24 h; metabolized via CYP2D6/CYP2C19 to nortriptyline. Accumulates in hepatic impairment.

Drug interactions

Avoid MAOIs, cisapride (QT), and agents lowering seizure threshold.

CYP2D6 inhibitors increase levels; enzyme inducers (carbamazepine) reduce efficacy.

Additive anticholinergic burden with antihistamines, antipsychotics.

Monitoring & safety checks

Discontinuation guidance

Gradually taper ≥4 weeks; abrupt cessation may cause cholinergic rebound, insomnia, irritability.

References

  1. Amitriptyline Prescribing Information — DailyMed
  2. CANMAT TCA guidance (2024)
  3. APA guidance on TCAs for chronic pain (2021)

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