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Tricyclic Antidepressant — Neuropathic Pain Agent Pregnancy: Use with caution — neonatal withdrawal syndrome reported; consult specialist

Amitriptyline (Orthopaedic — Neuropathic Pain)

Brand names: Tryptizol, Amitriptyline

Adult dose

Dose: 10–75 mg at night (neuropathic pain — lower doses than antidepressant use)
Route: Oral
Frequency: Once daily at bedtime
Max: 75 mg/day for neuropathic pain; 150–200 mg/day for depression (different indication)
Start at 10 mg at night; increase by 10–25 mg every 2 weeks. Take at bedtime — sedating effect is a benefit for pain patients with sleep disturbance. Analgesic effect is independent of antidepressant effect and occurs at lower doses.

Paediatric dose

Route:
Not licensed for neuropathic pain in children under 18 — seek specialist opinion; some use in paediatric chronic pain services under specialist guidance

Dose adjustments

Renal

Use with caution in renal impairment — metabolites accumulate; increase sedation and anticholinergic effects

Hepatic

Reduce dose in hepatic impairment — extensive hepatic metabolism; accumulation risk

Clinical pearls

  • NICE NG59 (Neuropathic Pain): amitriptyline is first-line for neuropathic pain (with duloxetine, gabapentin, or pregabalin) — analgesic effect via serotonin and noradrenaline reuptake inhibition and sodium channel blockade at dorsal horn
  • Analgesic doses are lower than antidepressant doses: neuropathic pain typically responds to 10–50 mg/night; patients should be informed that it is prescribed for nerve pain, not depression — reduces stigma and improves compliance
  • Elderly patients: amitriptyline has highest anticholinergic burden among TCAs — significant fall risk, confusion, urinary retention, and cognitive impairment; STOPP/START criteria advise AGAINST amitriptyline in elderly patients as first-line; prefer duloxetine or pregabalin
  • Post-amputation phantom limb pain and CRPS: amitriptyline is widely used — limited RCT evidence but extensive clinical experience; used as part of multimodal pain management
  • Overdose risk: tricyclics are highly cardiotoxic in overdose — assess suicide risk before prescribing; prescribe small quantities if risk identified; amitriptyline causes wide complex tachycardia and refractory VF in overdose

Contraindications

  • Recent MI (within 3 months)
  • Arrhythmias — especially heart block or QTc prolongation
  • Mania
  • Severe liver disease
  • Concurrent MAO inhibitors (within 14 days)

Side effects

  • Sedation — often beneficial for patients with pain-related insomnia; most common side effect
  • Anticholinergic effects — dry mouth, urinary retention, constipation, blurred vision
  • QTc prolongation — cardiac risk in overdose and in combination with other QT-prolonging drugs
  • Postural hypotension — fall risk in elderly; start low and review
  • Weight gain
  • Cognitive impairment (elderly)

Interactions

  • MAO inhibitors — potentially fatal interaction (serotonin syndrome, hyperpyrexia); avoid within 14 days
  • QT-prolonging drugs (antipsychotics, ciprofloxacin, erythromycin) — additive QTc prolongation
  • CNS depressants — additive sedation
  • Tramadol — serotonin syndrome risk; additive convulsant potential

Monitoring

  • ECG at baseline if cardiac risk factors (QTc assessment)
  • Blood pressure (postural hypotension — elderly)
  • Pain score at each review
  • Anticholinergic side effects
  • Cognitive function in elderly

Reference: BNFc; BNF 90; NICE NG59 (Neuropathic Pain 2019); STOPP/START Criteria v3; SPC Amitriptyline; Cochrane Review (Amitriptyline Neuropathic Pain). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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