What is the recommended dose of amitriptyline for migraine prophylaxis in adults?

Amitriptyline Dosing for Migraine Prophylaxis

For migraine prophylaxis in adults, start amitriptyline at 10-25 mg at bedtime and titrate to a target dose of 25-50 mg daily, with a maximum effective range of 75-150 mg daily if needed. 1

Starting Dose

• Begin with 10-25 mg at bedtime to minimize side effects and improve tolerability 1
• The most common starting dose in clinical practice is 10 mg daily, which has been shown to be effective and well-tolerated 2
• Dosing at night utilizes the sedative effect to improve sleep, which is particularly beneficial for migraine patients 1

Target Therapeutic Dose

• The effective dose for most patients is 25-50 mg daily 1
• Clinical trials demonstrating efficacy have used doses between 25-150 mg daily 1
• Real-world evidence shows that 58% of patients achieve benefit at doses of 10-25 mg, lower than traditional trial doses 2

Titration Schedule

• Increase the dose slowly by 10-25 mg increments every 2 weeks until therapeutic benefit is achieved or side effects limit further increases 3
• The goal is to reach 75-150 mg daily or 1-1.5 mg/kg at bedtime for optimal prophylaxis 3
• Slower titration improves tolerability and medication persistence 3

Duration Before Assessing Efficacy

• Clinical benefits may take 2-3 months to fully develop, so adequate trial duration is essential 1, 3
• Do not discontinue therapy before 8 weeks (minimum) to 12 weeks (optimal) unless intolerable side effects occur 1
• After achieving stability for several months, consider tapering or discontinuing to assess ongoing need 3

Indications for Use

Amitriptyline prophylaxis is indicated when patients have: 1, 3

• ≥2 migraine attacks per month producing disability lasting ≥3 days per month
• Use of acute medications more than twice per week
• Failure of or contraindications to acute migraine treatments
• Presence of uncommon migraine conditions (prolonged aura, hemiplegic migraine)

Comparative Efficacy

• Amitriptyline is the only antidepressant with consistent evidence supporting efficacy in migraine prevention 1
• It appears superior to propranolol for patients with mixed migraine and tension-type headache 3, 4
• Amitriptyline is equivalent to topiramate in reducing migraine frequency but differs in side effect profile (weight gain vs. weight loss) 5

Common Side Effects to Monitor

• Anticholinergic effects: dry mouth, constipation, urinary hesitancy, blurred vision 3
• Sedation and drowsiness: most common, reported in 11% of patients 2
• Weight gain: average 2.4 kg gain reported in comparative trials 5
• Prolonged QTc on ECG: requires baseline ECG in at-risk patients 3

Critical Pitfalls to Avoid

• Do not use amitriptyline as acute treatment—it is strictly a preventive medication 1
• Do not discontinue before 8-12 weeks unless side effects are intolerable, as benefits develop slowly 1
• Do not start at high doses—this increases side effects and reduces medication persistence 2
• Do not overlook that low doses (10-25 mg) are often effective in real-world practice, despite higher doses used in clinical trials 2

Special Populations

• In children with frequent headaches, use 1 mg/kg per day as the target dose, which has shown 84% improvement rates with minimal side effects 6
• For chronic daily headache (≥17 headache days per month), amitriptyline shows superior efficacy to placebo with 46% achieving ≥50% improvement at 16 weeks 7