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Tricyclic Antidepressant (TCA) Pregnancy: Avoid if possible — neonatal withdrawal and anticholinergic effects in neonate. Use lowest effective dose; sertraline preferred.

Amitriptyline

Brand names: Tryptizol, Elavil

Adult dose

Dose: Depression: 75–150mg OD at night initially (start 25–50mg OD); maximum 200mg OD. Neuropathic pain / migraine prophylaxis: 10–25mg at night initially; usual dose 25–75mg ON; maximum 75mg ON. Nocturnal enuresis (off-label): 10–25mg at night.
Route: Oral
Frequency: Once daily at night (sedating — most of dose taken at bedtime)
Max: 200mg OD (depression); 75mg ON (neuropathic pain/migraine — higher doses increase toxicity risk without additional benefit)
At doses used for neuropathic pain and migraine prophylaxis (10–75mg), amitriptyline is not a therapeutic antidepressant dose. Sedation is a useful property for insomnia comorbidity. High toxicity in overdose — cardiotoxicity (QRS widening, VT), anticholinergic toxidrome, and seizures. Low therapeutic index — prescribe cautiously in patients with suicide risk.

Paediatric dose

Route: Oral
Frequency: Once daily at night
Max: 75mg ON
BNFc: Neuropathic pain (2–11 years): 100–500 micrograms/kg ON (max 25mg); (12–17 years): 10mg ON, up to 75mg ON. Nocturnal enuresis (6–10 years): 10–20mg ON; (11–16 years): 25–50mg ON. Not licensed for depression under 18 years. Seek specialist paediatric opinion.

Dose adjustments

Renal

Use with caution in renal impairment — risk of accumulation and CNS toxicity.

Hepatic

Avoid in severe hepatic impairment — impaired metabolism; accumulation and sedation risk.

Clinical pearls

  • Overdose antidote: IV sodium bicarbonate is the specific treatment for TCA cardiac toxicity (QRS widening >100ms) — alkalinisation reverses sodium channel blockade. Bolus 1–2 mEq/kg IV, repeat until QRS narrows
  • TCA overdose is a medical emergency — even small ingestions in children are potentially fatal; serious toxicity at 10–20mg/kg
  • Low-dose amitriptyline (10–30mg ON) is widely used off-label for neuropathic pain, migraine prophylaxis, and IBS — NICE NG59 includes amitriptyline as first-line for neuropathic pain
  • Anticholinergic burden: avoid in elderly (Beers Criteria) — risk of delirium, urinary retention, falls, cognitive decline

Contraindications

  • Recent MI (within 3 months)
  • Arrhythmias, heart block
  • Mania (may precipitate)
  • Closed-angle glaucoma
  • Urinary retention
  • MAOIs (within 14 days — risk of severe hypertension / serotonin syndrome)
  • Hypersensitivity to amitriptyline or other TCAs

Side effects

  • Sedation (useful therapeutically at night)
  • Dry mouth, constipation, urinary retention, blurred vision (anticholinergic)
  • Orthostatic hypotension (alpha-1 blockade — fall risk in elderly)
  • QTc prolongation, heart block (cardiotoxic)
  • Weight gain
  • Confusion / delirium (elderly)
  • Serotonin syndrome (overdose)
  • Lowered seizure threshold

Interactions

  • MAOIs — contraindicated
  • Antiarrhythmics, other QT-prolonging drugs — additive cardiac toxicity
  • CNS depressants, alcohol — additive sedation
  • Anticholinergic drugs — additive effects (urinary retention, confusion)
  • Adrenaline (epinephrine) — amitriptyline blocks noradrenaline reuptake; risk of severe hypertension — avoid felypressin-free local anaesthetic or use with caution

Monitoring

  • ECG (QTc) — before starting if cardiac risk factors or dose >100mg
  • Blood pressure (orthostatic hypotension — sit-to-stand BP)
  • Weight (long-term)
  • Anticholinergic side effects review

Reference: BNFc; BNF 90; NICE NG59 (Neuropathic Pain); NICE CG150 (Headaches). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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