What is the recommended dose of amitriptyline (tricyclic antidepressant) for migraine prophylaxis?

Amitriptyline Dosing for Migraine Prophylaxis

For migraine prevention, start amitriptyline at 10-25 mg at bedtime and titrate gradually to a target dose of 30-150 mg daily, with most patients achieving benefit at 50-100 mg daily. 1, 2

Starting and Titration Strategy

• Begin with 10-25 mg at bedtime and increase slowly over weeks to months to minimize side effects and improve tolerability 1
• The FDA-approved outpatient starting regimen is 75 mg daily in divided doses, though clinical practice typically starts lower for prophylaxis 2
• An alternative initiation method is 50-100 mg at bedtime, increased by 25-50 mg increments as needed 2

Target Therapeutic Dose

• The recommended therapeutic range is 30-150 mg daily for migraine prophylaxis 1, 3
• Most patients respond adequately to 50-100 mg daily, which should be the initial target 1
• Some patients may require up to 150 mg daily if lower doses prove insufficient 1, 2
• Hospitalized patients may need higher doses (100-200 mg daily), with rare cases requiring up to 300 mg daily 2

Timeline for Response

• Clinical benefits may not become apparent for 2-3 months after reaching therapeutic dosing 1, 4
• An adequate trial requires maintaining the target dose for at least 2-3 months before declaring treatment failure 1
• Sedative effects may appear before the therapeutic effect on headache frequency 2

Maintenance and Duration

• Once satisfactory improvement is achieved, the usual maintenance dose is 50-100 mg daily (some patients respond to as little as 40 mg daily) 2
• The total daily dose can be given as a single bedtime dose for convenience 2
• Continue treatment for 6-12 months, then attempt to taper to the lowest effective dose or discontinue 1, 5

Patient Selection Considerations

• Amitriptyline is superior to propranolol for patients with mixed migraine and tension-type headache 1
• For pure migraine without tension-type features, propranolol may be preferred over amitriptyline 1
• Consider amitriptyline as first-line in patients with comorbid depression or tension-type headaches 5, 3

Special Populations

• Adolescents and elderly patients: Start with 10 mg three times daily plus 20 mg at bedtime (total 50 mg daily) if higher doses are not tolerated 2
• Pediatric patients (≥12 years): Use 1 mg/kg daily as the target dose, with 84% of children showing improvement and minimal side effects 6
• Not recommended for children under 12 years due to lack of experience 2

Common Side Effects to Anticipate

• Weight gain, drowsiness, and anticholinergic symptoms (dry mouth, constipation) are the most frequent adverse effects 1
• These side effects often necessitate the low-start, slow-titration approach 1
• Plasma level monitoring may be useful in elderly patients or when toxicity is suspected, though dosing should be based on clinical response 2

Important Clinical Caveats

• Limit acute migraine medication use to no more than twice weekly to prevent medication-overuse headaches, even when on prophylaxis 7
• If amitriptyline proves ineffective or poorly tolerated after an adequate trial, consider switching to beta-blockers (propranolol 80-240 mg daily) or anticonvulsants (topiramate 50-200 mg daily, divalproex sodium 600-1500 mg daily) 1, 4
• Patients should maintain a headache diary to objectively assess treatment response 4, 8