What are the first-line treatment options for headache prophylaxis, particularly for migraines?

Headache Prophylaxis Treatment

First-Line Prophylactic Medications

For migraine prophylaxis, start with propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (50 mg twice daily for 100 mg/day total), or candesartan, as these have the strongest evidence for efficacy and are recommended as first-line agents. 1

Beta-Blockers

• Propranolol (80-240 mg/day) is FDA-approved and has strong evidence for migraine prevention, making it a preferred first-line choice 1
• Timolol (20-30 mg/day) also has strong evidence and FDA approval 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily) with demonstrated efficacy in reducing migraine frequency by approximately 2 attacks per month 1, 2
• Start at 25 mg/day and titrate by 25-50 mg weekly to minimize side effects 2, 3
• The 200 mg/day dose shows no additional efficacy over 100 mg/day but causes more tolerability issues 2, 4
• Most common side effects include paresthesia, fatigue, decreased appetite, nausea, and weight loss 2
• Particularly useful for patients concerned about weight gain or who are overweight, as it typically causes weight loss 2

Angiotensin Receptor Blockers

• Candesartan is especially useful for patients with comorbid hypertension 1

Second-Line Prophylactic Medications

When first-line agents fail or are contraindicated, consider these options:

• Amitriptyline (30-150 mg/day) is particularly effective in patients with mixed migraine and tension-type headache 1
• Valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 1, 5
• Flunarizine is effective where available 1
• Memantine has weak evidence for episodic migraine prevention 5
• Lisinopril has weak evidence for episodic migraine prevention 5
• Oral magnesium has weak evidence but may be considered 5

CGRP Monoclonal Antibodies (Third-Line)

When first- and second-line preventive treatments have failed or are contraindicated, CGRP monoclonal antibodies should be considered. 1

• Erenumab, fremanezumab, or galcanezumab have strong recommendations for prevention of episodic or chronic migraine 5
• Intravenous eptinezumab has weak evidence for episodic or chronic migraine prevention 5
• Efficacy should be assessed only after 3-6 months of treatment, as these agents require longer trial periods than oral medications 1
• Atogepant has weak evidence for episodic migraine prevention 5
• Rimegepant has insufficient evidence for migraine prevention 5

OnabotulinumtoxinA

• Recommended for chronic migraine prevention only (not episodic migraine) 5
• Requires 6-9 months to assess efficacy 1
• Specifically recommended against for episodic migraine prevention 5

Implementation Strategy

Indications for Starting Prophylaxis

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1
• Using abortive medication more than twice per week (risk of medication overuse headache) 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1

Titration and Trial Period

• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow an adequate trial period of 2-3 months for oral agents before determining efficacy 1
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 1

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1
• Calculate percentage reduction in monthly migraine days to quantify success 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (more than twice weekly), which interferes with preventive treatment 1
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Inadequate duration of preventive trial (less than 2-3 months for oral agents) 1
• Prescribing valproate to women of childbearing potential 1
• Not addressing comorbidities that influence treatment selection (e.g., hypertension favoring candesartan, weight concerns favoring topiramate) 1

Non-Pharmacological Adjuncts

• Neuromodulatory devices, biobehavioral therapy, or acupuncture can be considered as adjuncts or stand-alone treatments when medications are contraindicated 1
• Limited evidence exists for physical therapy, spinal manipulation, and dietary approaches 1