Recommended Dosing for Amitriptyline and Propranolol in Headache Prevention
For migraine prevention, start amitriptyline at 30-150 mg daily or propranolol at 80-240 mg daily, as both are first-line agents with good evidence for efficacy. 1
First-Line Agent Selection
Both amitriptyline and propranolol are designated as first-line preventive agents for migraine by the AAFP/ACP-ASIM guidelines. 1 The choice between them depends on your patient's specific headache pattern and comorbidities:
Amitriptyline Dosing
- Standard dosing range: 30-150 mg daily 1
- Practical starting approach: Begin with 10-25 mg at bedtime 2
- Increase gradually every 1-2 weeks as tolerated 1
- Most patients in real-world practice respond to lower doses (10-25 mg daily) than used in clinical trials 3
- Amitriptyline is superior to propranolol when patients have mixed migraine and tension-type headache 1
- Particularly effective for chronic daily headache (≥17 days/month), showing 46% of patients achieving ≥50% improvement at 16 weeks 4
Propranolol Dosing
- Standard dosing range: 80-240 mg daily 1, 5
- FDA-approved starting dose: 80 mg once daily (extended-release formulation) 5
- Increase to 120 mg once daily or higher until adequate control is achieved 5
- Usual maintenance dosage: 120-160 mg once daily 5
- Maximum studied dose: 640 mg daily, though most patients respond to lower doses 5
- Propranolol is superior to amitriptyline for patients with migraine alone (without tension-type features) 1
Comparative Efficacy Evidence
A recent 2024 comparative study found amitriptyline more effective than propranolol at reducing migraine frequency, duration, and severity over 3 months of treatment. 6 However, the AAFP/ACP-ASIM guidelines note that one comparative trial suggested propranolol superiority in pure migraine, while amitriptyline was better for mixed headache types. 1
Titration Strategy
Start low and titrate slowly over weeks to months: 1
- Clinical benefits may not become apparent for 2-3 months 1, 7
- Increase dose gradually until benefits are achieved without adverse effects 1
- An adequate trial requires reaching therapeutic dosing for at least 2-3 months before declaring treatment failure 1, 7
Common Pitfalls to Avoid
Abandoning therapy too early: Many clinicians discontinue preventive medications before the 2-3 month window needed to assess full efficacy. 1, 7
Inadequate dosing of amitriptyline: While real-world data shows efficacy at 10-25 mg daily 3, guideline-recommended dosing is 30-150 mg daily for optimal prevention. 1 Consider that lower doses may work for some patients, but don't assume failure without reaching at least 30 mg daily.
Not accounting for headache type: Using propranolol for mixed migraine/tension-type headache when amitriptyline would be more appropriate. 1
Side Effect Profile
Amitriptyline: Weight gain, drowsiness, anticholinergic symptoms (dry mouth, constipation). 1 In real-world practice, daytime fatigue occurs in approximately 11% of patients, but low-dose therapy (10-25 mg) is generally well-tolerated with 85% medication persistence. 3
Propranolol: Fatigue, depression, nausea, dizziness, insomnia—generally fairly well tolerated. 1
When to Discontinue or Taper
After achieving a period of stability (typically several months of good headache control), consider tapering or discontinuing the medication. 1 For propranolol specifically, withdraw gradually over several weeks depending on patient age, comorbidity, and dose. 5