amitriptyline

Adjunctive therapy

Brands: Elavil

Last reviewed 2025-10-05

Reviewed by PsychMed Editorial Team.

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Quick answers

What is amitriptyline?
Amitriptyline is an older tricyclic antidepressant. Today it is often used at low bedtime doses for neuropathic pain, migraine prevention, or sleep continuity, and at higher doses for depression when first-line options have not worked or were not tolerated.
What is Elavil?
Elavil is a brand name for amitriptyline.
What is Elavil (amitriptyline) used for?
Label indications include: Depression; off-label for neuropathic pain and migraine prophylaxis.
What drug class is Elavil (amitriptyline)?
Tertiary-amine tricyclic antidepressant that inhibits serotonin and norepinephrine reuptake while strongly antagonising histamine H1, muscarinic, and α1-adrenergic receptors; sodium-channel blockade contributes to analgesia.
What strengths does Elavil (amitriptyline) come in?
Oral tablets: 10 mg (scored), 25 mg, 50 mg, 75 mg, 100 mg, 150 mg.

Snapshot

Class: Adjunctive therapy
Common US brands: Elavil
Therapeutic drug monitoring recommended; reference range 80–250 ng/mL.
Last reviewed: 2025-10-05

Label indications

Depression; off-label for neuropathic pain and migraine prophylaxis.

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Clinical Highlights

Amitriptyline is an older tricyclic antidepressant. Today it is often used at low bedtime doses for neuropathic pain, migraine prevention, or sleep continuity, and at higher doses for depression when first-line options have not worked or were not tolerated. Strong anticholinergic, antihistaminic, and α1-adrenergic blockade produce sedation, constipation, cognitive slowing, and orthostatic hypotension. Slow titration and fall-risk mitigation are common, especially in older adults.

Low nightly doses (10–50 mg) are valuable for neuropathic pain, migraine prophylaxis, insomnia, and functional GI disorders, while higher doses (100–300 mg/day) require specialist oversight.
Overdose is highly cardiotoxic; many clinicians dispense limited quantities and emphasize secure storage, especially when suicide risk is elevated.
Therapeutic drug monitoring (combined amitriptyline + nortriptyline 80–250 ng/mL) clarifies non-response, toxicity, or adherence concerns.
In bipolar depression, antidepressants are typically combined with a mood stabiliser; when discontinuing, tapering is usually gradual to avoid cholinergic rebound.
The compare tool and amitriptyline evidence feed can support shared decision-making with psychiatry and pain teams.

Indications & Niche Uses

Major depressive disorder after inadequate response to SSRIs/SNRIs or when prior TCA response exists. Neuropathic pain syndromes (diabetic neuropathy, post-herpetic neuralgia, fibromyalgia) and chronic tension or migraine headaches.

Functional gastrointestinal disorders (IBS, functional dyspepsia) and sleep-maintenance insomnia requiring sedating adjuncts.
Paediatric nocturnal enuresis (off-label) with cardiology screening when family cardiac history exists.

Dosing & Formulations

Oral tablets: 10 mg (scored), 25 mg, 50 mg, 75 mg, 100 mg, 150 mg; tablets can be crushed or compounded into 10 mg/mL solution. Depression: start 25–50 mg HS; increase by 25–50 mg every 3–7 days toward 100–150 mg/day (max 300 mg with ECG monitoring).

Pain/migraine: initiate 10–25 mg HS; titrate by 10–25 mg every 1–2 weeks up to 50–100 mg as tolerated.
Older adults/frail patients: begin 5–10 mg HS, titrate slowly, and consider switching to nortriptyline if cognition or anticholinergic burden becomes limiting.
Retitrate from 10–25 mg if therapy lapses ≥3 days to avoid orthostatic collapse and arrhythmias.

Monitoring & Safety

Baseline and follow-up vitals, weight/BMI, and ECG for adults >40 years or with cardiac disease; monitor orthostatic blood pressures during titration. Screen for suicidality during initiation/dose changes and monitor for manic switch in bipolar spectrum disorders.

Reassess metabolic parameters (lipids, glucose) if weight gain emerges; evaluate bowel function, urinary retention, and cognitive status at each visit.
Consider therapeutic drug monitoring when non-response, toxicity, or interacting medications complicate management.

Adverse Effects

Sedation, cognitive slowing, and residual morning grogginess—mitigated by bedtime dosing and slow titration. Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision) requiring hydration and bowel regimens.

Orthostatic hypotension and tachycardia from α1 blockade; patients are often advised to rise slowly and avoid dehydration.
Weight gain, sweating, tremor, and sexual dysfunction; monitor BMI and discuss lifestyle strategies.
Cardiac conduction delays, QT prolongation, and seizures at high serum levels; lethal within narrow overdose margins (10–20 mg/kg).

Drug Interactions

Contraindicated with MAOIs—maintain a 14-day washout to avoid serotonin syndrome/hypertensive crisis. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) and CYP2C19/CYP3A4 inhibitors (fluvoxamine, omeprazole, macrolides, azoles) raise serum concentrations; reduce the dose or monitor levels.

Enzyme inducers (carbamazepine, rifampin, phenytoin, St John’s wort, smoking) lower exposure and may necessitate dose increases.
Serotonergic agents (SSRIs, SNRIs, triptans, linezolid, tramadol) elevate serotonin syndrome risk—monitor for clonus and autonomic instability.
Additive CNS depression or anticholinergic load with antihistamines, antipsychotics, opioids, alcohol, or benzodiazepines increases falls and confusion.
QT-prolonging medications (antiarrhythmics, macrolides, fluoroquinolones, antipsychotics) heighten arrhythmia risk; obtain ECG surveillance when combinations are unavoidable.

Special Populations

Older adults: start at 5–10 mg, titrate slowly, and monitor for delirium, falls, urinary retention, and SIADH. Pregnancy: Category C; weigh maternal benefit against neonatal withdrawal or hypotonia—avoid high doses near delivery.

Lactation: Low breast-milk transfer but monitor infants for sedation and feeding difficulty.
Hepatic impairment: reduce starting dose and extend titration interval; severe renal impairment warrants toxicity surveillance despite minimal renal clearance.
Paediatrics: cardiology review before enuresis treatment, and taper after 1–3 months to assess ongoing need.

Practice Notes & Counseling

Because overdose can be lethal, clinicians often dispense small quantities, emphasize secure storage, and discuss safety planning. Practical strategies for anticholinergic and orthostatic effects can include hydration, fibre intake, saliva substitutes, and gradual positional changes.

When discontinuing after ongoing use, tapering is typically gradual to prevent cholinergic rebound (flu-like symptoms, insomnia, nausea).
In bipolar depression, mood-stabiliser co-therapy and close early follow-up are commonly used to reduce switch risk.
Use the compare tool and bipolar disorder hub to coordinate multidisciplinary care.

Evidence Pointers

CANMAT depression guidelines list amitriptyline as a third-line agent for treatment-resistant MDD due to side-effect burden. NICE and American Academy of Neurology neuropathic pain guidelines endorse low-dose TCAs when gabapentinoids or SNRIs are insufficient.

Migraine prevention guidelines place amitriptyline among first-line oral options, particularly when insomnia or weight loss coexist.
Therapeutic drug monitoring consensus statements target combined amitriptyline + nortriptyline troughs of 80–250 ng/mL.

References

Amitriptyline Hydrochloride Tablets, USP — DailyMed (2021)
CANMAT 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder — Canadian Journal of Psychiatry (2016)
Amitriptyline for neuropathic pain in adults — Cochrane Database of Systematic Reviews (2015)