Amitriptyline (Elavil) for Migraine Prevention
Amitriptyline is a first-line preventive agent for episodic migraine, particularly when patients have comorbid depression, sleep disturbances, or mixed migraine with tension-type headache features. 1, 2
Evidence Base and Efficacy
Amitriptyline has the strongest evidence among tricyclic antidepressants for migraine prevention, with demonstrated efficacy in reducing headache frequency by more than 50% in approximately 72% of patients. 3, 4 The medication works through multiple mechanisms including inhibition of noradrenaline and serotonin reuptake and 5-HT2-receptor antagonism. 5
However, a critical limitation exists: there is no robust data from randomized controlled trials supporting amitriptyline's use specifically for chronic migraine (≥15 headache days per month), though it remains commonly used in clinical practice for this indication. 6
When to Use Amitriptyline
Primary Indications
- Episodic migraine with ≥2 attacks per month producing disability lasting ≥3 days per month 1, 7
- Mixed migraine and tension-type headache, where amitriptyline is superior to propranolol 1, 7
- Comorbid depression or sleep disturbances, as the medication addresses both conditions simultaneously 6
- Patients overusing acute medications (≥2 times per week) 7
- Contraindication to or failure of acute migraine treatments 1
Comparative Effectiveness
- Amitriptyline is more effective than fluoxetine (71% vs 56% response rate) and maprotiline (71% vs 38% response rate) for migraine prevention 5
- For pure migraine without tension-type features, propranolol (80-240 mg/day) is superior to amitriptyline 1, 7
- Nortriptyline lacks evidence for efficacy despite being in the same drug class 1
Dosing Strategy
Initiation and Titration
- Start with 10-25 mg at bedtime 1, 7
- Gradually titrate to 30-150 mg/day as tolerated 1, 2
- Increase slowly over weeks to months to minimize side effects 8
Duration of Trial
- Allow 2-3 months at therapeutic dose before declaring treatment failure, as clinical benefits may not become apparent immediately 6, 1, 7
- After a period of stability, consider tapering or discontinuing treatment 6
Side Effects and Monitoring
Common Adverse Events
- Weight gain (particularly problematic; consider topiramate instead for obese patients) 6, 1, 7
- Drowsiness (can be beneficial for comorbid insomnia) 6, 4
- Anticholinergic symptoms: dry mouth, constipation 1, 7
Special Populations
- Elderly patients: Use caution due to increased risk of anticholinergic effects 6
- Depression and extrapyramidal symptoms can occur, particularly in older individuals 6
Critical Pitfalls to Avoid
Medication Overuse
- Educate patients to limit acute medication use to prevent medication overuse headache (MOH), which can worsen migraine frequency 6
- Avoid interfering medications like ergotamine during preventive treatment 6
Inadequate Trial Duration
- Do not discontinue prematurely—many clinicians stop treatment before the 2-3 month mark needed to assess true efficacy 6, 1
Wrong Patient Selection
- For chronic migraine specifically, topiramate, onabotulinumtoxinA, and CGRP monoclonal antibodies have proven efficacy, while amitriptyline does not have robust RCT data for this indication 6
- For pure migraine without tension features, propranolol is the better choice 1, 7
Alternative First-Line Options
When amitriptyline is ineffective, poorly tolerated, or contraindicated: