Tricyclic Antidepressant — Neuropathic Pain Agent Pregnancy: Not recommended during pregnancy unless clearly necessary and only after careful risk/benefit consideration; neonatal withdrawal symptoms can occur with chronic use or use in the final weeks of pregnancy

Amitriptyline (Orthopaedic — Neuropathic Pain)

Brand names: Tryptizol, Amitriptyline

Used in: Headache & Migraine

This entry covers low-dose amitriptyline, a tricyclic antidepressant used off-label in the orthopaedic setting for chronic neuropathic and musculoskeletal pain rather than for depression.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Neuropathic pain (adults): 25 mg–75 mg daily in the evening

Route: Oral

Frequency: Once daily in the evening, or divided into two doses

Max: A single dose above 75 mg is not recommended; doses above 100 mg should be used with caution

SPC neuropathic-pain dose (also covers chronic tension-type headache prophylaxis and migraine prophylaxis). Individually titrate to the dose that provides adequate analgesia with tolerable adverse reactions; use the lowest effective dose for the shortest duration. Initial dose 10 mg–25 mg in the evening; increase by 10 mg–25 mg every 3–7 days as tolerated; analgesic effect normally seen after 2–4 weeks; treatment is symptomatic and may be needed for several years with regular reassessment. Elderly (>65 yr) / cardiovascular disease: start 10 mg–25 mg in the evening; doses above 75 mg with caution.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Recent myocardial infarction
Any degree of heart block or disorders of cardiac rhythm and coronary artery insufficiency
Concomitant treatment with MAOIs (monoamine oxidase inhibitors)
Severe liver disease
Children under 6 years of age

Side effects

Orthostatic hypotension (very common)
Palpitations, tachycardia (very common)
Somnolence, tremor, dizziness, headache, drowsiness, dysarthria (very common)
Dry mouth, constipation, nausea (very common)
Hyperhidrosis (very common)

Interactions

MAOIs — concomitant use contraindicated; may cause serotonin syndrome (14-day washout for irreversible non-selective MAOIs, 1 day for moclobemide)
Anaesthetics — may increase risk of arrhythmias and hypotension during tri/tetracyclic antidepressant therapy
QT-prolonging drugs — caution; cases of QT prolongation and arrhythmia reported

Clinical monograph

How it works

It inhibits reuptake of noradrenaline and serotonin and blocks several receptors, enhancing descending inhibitory pain pathways to produce an analgesic effect that is independent of its antidepressant action.

Prescribing in practice

Use cautiously in cardiovascular disease and avoid in recent myocardial infarction, arrhythmias and significant conduction disorders, as tricyclics are cardiotoxic in overdose and can prolong the QT interval.
Anticholinergic effects, sedation and falls risk are common, particularly in older patients, so start low and titrate slowly with a bedtime dose.
Avoid concurrent MAOIs and use care with other serotonergic or QT-prolonging drugs.

Monitoring

Monitor analgesic response, mood, and anticholinergic and cardiovascular adverse effects, especially during dose titration in older or comorbid patients.

Counselling the patient

Take at night as it can cause drowsiness; pain relief may take a couple of weeks and the dose used is lower than for depression.
Report palpitations, fainting, marked dry mouth, urinary difficulty or significant daytime sedation.

Evidence & guidelines

NICE guidance on neuropathic pain includes amitriptyline as a first-line option, supported by evidence of analgesic benefit at low doses.

Reference: NICE NG59 (Neuropathic Pain 2019); STOPP/START Criteria v3; SPC Amitriptyline; Cochrane Review (Amitriptyline Neuropathic Pain); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways