Tricyclic Antidepressant / Neuropathic Pain Agent Pregnancy: Only limited clinical data on exposed pregnancies; animal studies have shown reproductive toxicity. Not recommended during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit. With chronic use and administration in the final weeks of pregnancy, neonatal withdrawal symptoms can occur (irritability, hypertonia, tremor, irregular breathing, poor drinking, loud crying and possibly anticholinergic symptoms such as urinary retention and constipation). Breastfeeding: amitriptyline and its metabolites are excreted into breast milk (0.6-1% of the maternal dose) and a risk to the suckling child cannot be excluded — decide whether to discontinue breastfeeding or therapy.

Amitriptyline (Neuropathic Pain / Migraine)

Brand names: Tryptizol

Used in: Headache & Migraine

Amitriptyline is a tricyclic antidepressant used, at lower doses than for depression, for neuropathic pain and migraine prophylaxis.

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, prophylaxis of chronic tension-type headache and migraine prophylaxis: 25 mg to 75 mg daily; initial dose 10 mg to 25 mg in the evening, increased by 10 mg to 25 mg every 3 to 7 days as tolerated

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

Patients should be individually titrated to the dose that provides adequate analgesia with tolerable adverse reactions; generally the lowest effective dose should be used for the shortest duration required. The analgesic effect is normally seen after 2 to 4 weeks of dosing. Neuropathic pain treatment is symptomatic and may be needed for several years in many patients, with regular reassessment that continuation remains appropriate; the same applies to headache and migraine prophylaxis. Elderly over 65 years and patients with cardiovascular disease: start at 10 mg to 25 mg in the evening; doses above 75 mg should be used with caution; initiate in the lower dose range and increase according to individual response and tolerability. Known poor metabolisers of CYP2D6 or CYP2C19 may have higher plasma concentrations of amitriptyline and its active metabolite nortriptyline — consider a 50% reduction of the recommended starting dose; consider a lower dose if a strong CYP2D6 inhibitor (e.g. bupropion, quinidine, fluoxetine, paroxetine) is added. When stopping, withdraw gradually over several weeks. Separate SPC regimen for major depressive disorder (different, higher dose range — do not mix with the analgesic doses): adults initially 25 mg twice daily (50 mg daily), increased if necessary by 25 mg every other day up to 150 mg daily in two divided doses; elderly over 65 or cardiovascular disease initially 10-25 mg daily, up to 100-150 mg daily in two doses, with doses above 100 mg used with caution. Paediatric: amitriptyline should not be used in children and adolescents under 18 years for neuropathic pain or headache/migraine prophylaxis (nor for depression) as safety and efficacy have not been established. The SPC does contain a separate paediatric regimen for nocturnal enuresis from age 6 (a different indication that is not this page's) requiring an ECG before starting to exclude long QT syndrome and a treatment course of no more than 3 months — refer to the SPC and a children's formulary rather than extrapolating from the adult analgesic dose.

Dose adjustments

Renal

Renal impairment: can be given in usual doses to patients with renal failure. Hepatic impairment: careful dosing and, if possible, serum level determination is advisable (severe liver disease is a contraindication).

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.

US labelling (FDA)

Reference — US labelling, may differ from UK

DOSAGE AND ADMINISTRATION Oral Dosage Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. Initial Dosage for Adults For outpatients, 75 mg of amitriptyline hydrochloride a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. A sedative effect may be apparent before the antidepressant effect is noted, but an adequate therapeutic effect may take as long as 30 days to develop. An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg amitriptyline …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2024-06-12. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Recent myocardial infarction
Any degree of heart block, disorders of cardiac rhythm, or coronary artery insufficiency
Concomitant treatment with monoamine oxidase inhibitors (risk of serotonin syndrome) — allow 14 days after stopping an irreversible non-selective MAOI, and at least one day after stopping moclobemide, before starting amitriptyline; allow 14 days after stopping amitriptyline before starting an MAOI
Severe liver disease
Children under 6 years of age

Side effects

Somnolence, tremor, dizziness, headache, drowsiness, dysarthria (very common); disturbance in attention, dysgeusia, paraesthesia, ataxia (common); convulsion (uncommon)
Dry mouth, constipation, nausea (very common); diarrhoea, vomiting (uncommon); paralytic ileus (rare)
Palpitations, tachycardia (very common); atrioventricular block, bundle branch block (common); collapse conditions, worsening of cardiac failure (uncommon); arrhythmia (rare); cardiomyopathies, torsades de pointes (very rare)
Orthostatic hypotension (very common) — elderly patients are particularly susceptible; hypertension (uncommon)
Accommodation disorder (very common), mydriasis (common), acute glaucoma (very rare); hyperhidrosis (very common); congested nose (very common)
Aggression (very common); confusional state, decreased libido, agitation (common); hypomania, mania, anxiety, insomnia, nightmare (uncommon); delirium in elderly patients, hallucination, suicidal thoughts or behaviour (rare); hyponatraemia (common); micturition disorders (common) and urinary retention (uncommon)

Interactions

MAOIs — contraindicated; simultaneous administration may cause serotonin syndrome (agitation, confusion, tremor, myoclonus, hyperthermia)
Strong CYP2D6 inhibitors (e.g. bupropion, quinidine, fluoxetine, paroxetine) — consider a lower amitriptyline dose (§4.2, cross-referencing §4.5)
QT-prolonging medicines — caution; also caution in significant bradycardia, uncompensated heart failure and electrolyte disturbance (hypokalaemia, hyperkalaemia, hypomagnesaemia), which increase proarrhythmic risk
Anaesthetics given during tricyclic/tetracyclic antidepressant therapy may increase the risk of arrhythmias and hypotension — if possible discontinue several days before surgery, and inform the anaesthetist if emergency surgery is unavoidable
Thyroid medication / hyperthyroidism — great care needed, as cardiac arrhythmias may develop
The §4.5 text was not captured in this source extract, so the interaction list is incomplete. US labelling additionally flags topiramate (large increases in amitriptyline concentration in some patients) and cisapride (contraindicated — increased QT interval and arrhythmia risk)

Clinical monograph

How it works

It inhibits the reuptake of noradrenaline and serotonin, modulating descending pain pathways; its analgesic effect in neuropathic pain is independent of any antidepressant action.

Prescribing in practice

Tricyclics are dangerous and cardiotoxic in overdose; prescribe with caution and consider the quantity supplied in patients at risk.
Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), sedation and postural hypotension are common; use with caution in the elderly.
Use with caution in cardiovascular disease; sedation may impair driving and skilled tasks.

Monitoring

Review analgesic benefit against anticholinergic and sedative burden, particularly in older patients. Monitor blood pressure for postural drops and assess cardiovascular status before and during treatment where relevant.

Counselling the patient

Take it in the evening, as it can make you drowsy; this often improves after the first few weeks.
Do not drive or operate machinery until you know how it affects you.
Do not stop taking it suddenly; your dose should be reduced gradually.

Evidence & guidelines

Guideline-recommended for neuropathic pain (NICE CG173) and migraine prophylaxis (NICE CG150).

Reference: NICE NG193 Neuropathic Pain; NICE NG150 Migraine; 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