What prophylactic medication options are available for migraines not controlled by abortive therapy?

Prophylactic Medication for Migraine Not Controlled by Abortive Therapy

For migraines requiring prophylaxis, start with propranolol (80-240 mg/d), timolol (20-30 mg/d), amitriptyline (30-150 mg/d), divalproex sodium (500-1500 mg/d), or sodium valproate (800-1500 mg/d) as first-line agents. 1

When to Initiate Prophylactic Therapy

You should start prophylaxis when patients meet any of these criteria:

• Two or more attacks per month producing disability lasting 3 or more days 1
• Contraindication to or failure of acute treatments 1
• Use of abortive medication more than twice per week (critical threshold to prevent medication overuse headache) 1, 2
• Presence of uncommon migraine conditions including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1

First-Line Prophylactic Medications

Beta-Blockers (Preferred for Hypertension or Tachycardia)

• Propranolol 80-240 mg/d 1, 3
• Timolol 20-30 mg/d 1
• Nadolol or metoprolol 3
• Particularly useful in patients with comorbid hypertension or tachycardia 4
• Avoid in patients with frequent aura 5

Tricyclic Antidepressants (Preferred for Comorbid Depression/Anxiety or Tension-Type Headache)

• Amitriptyline 30-150 mg/d 1, 3
• First choice when migraine coexists with tension-type headaches or depression 5, 4
• Use carefully due to anticholinergic effects 4

Anticonvulsants (Preferred for High BMI Patients)

• Divalproex sodium 500-1500 mg/d 1, 3
• Sodium valproate 800-1500 mg/d 1
• Topiramate (strong recommendation for both episodic and chronic migraine) 3
• Topiramate is the only prophylactic that may lead to weight loss, making it ideal for patients concerned about weight gain 4
• Caution: Topiramate associated with cognitive adverse effects 4

Angiotensin Receptor Blockers/ACE Inhibitors (Preferred for Hypertensive Patients)

• Candesartan (strong recommendation) 3
• Lisinopril (weak recommendation) 3
• Preferable in patients with comorbid hypertension 4

Calcium Channel Blockers

• Verapamil (weak recommendation) 3
• Flunarizine (limited availability in some countries including the United States) 4, 3

Second-Line and Alternative Options

Nutraceuticals (Low Side Effect Strategy)

• Riboflavin (strong recommendation) 3
• Magnesium citrate (strong recommendation, particularly useful during pregnancy) 4, 3
• Coenzyme Q10 (strong recommendation) 3
• Butterbur (strong recommendation) 3
• These have lower efficacy but minimal severe adverse effects 4

Other Medications

• Gabapentin (strong recommendation) 3
• Venlafaxine (weak recommendation, useful for comorbid depression/anxiety) 3
• Pizotifen (weak recommendation, unavailable in United States) 3

Medications with Proven Efficacy but Significant Concerns

• Methysergide: Very effective but supplanted due to association with retroperitoneal fibrosis 1, 4
• Aspirin: Particularly useful in patients needing platelet inhibitors, but consider gastrointestinal bleeding risk 4

Newer CGRP-Targeted Therapies

• Atogepant: Weak recommendation for episodic migraine prevention, with cost considerations being a significant factor 2
• Requires 2-3 months for full therapeutic effect 2
• If inadequate after 2-3 months, consider switching to CGRP monoclonal antibodies, candesartan, telmisartan, or topiramate 2

Implementation Strategy

Dosing and Titration

• Start at low doses and gradually titrate to target dose to minimize adverse effects 2, 5
• Reach recommended daily dose only if tolerance permits 5

Assessment Period

• Assess efficacy after 2-3 months while patient maintains a headache diary 1, 5
• Allow 2-3 months for full therapeutic effect before declaring treatment failure 2

Duration of Treatment

• Continue successful treatment for 6-12 months 5
• Then attempt to taper dose to find minimum active dose or discontinue 5

Critical Pitfalls to Avoid

Medication Overuse Headache

• Limit acute medication use to no more than twice weekly to prevent medication overuse headache 2
• If needing acute medication more frequently, reassess preventive regimen rather than increasing abortive medication frequency 2
• Excessive acute medication intake is itself a strong indication for prophylactic treatment 1, 5

Treatment Failure Assessment

Before declaring prophylaxis ineffective, verify:

• No overuse of symptomatic medications 5
• Adequate compliance 5
• No drug interactions with abortive medications 5

Combining Prophylactic and Acute Therapy

• Continue daily prophylactic therapy even when using acute medications - they serve complementary roles 2
• Acute medications (e.g., rizatriptan 10 mg) can be taken as needed for individual attacks while maintaining daily prophylaxis 2
• Document migraine frequency and acute medication use to monitor for overuse patterns 2

Special Considerations

Patient Selection Factors

• Weight concerns: Avoid medications causing weight gain in young women and athletes; choose topiramate 5, 4
• Athletic patients: May not tolerate beta-blockers 5
• Pregnancy/lactation: Discuss adverse effects before initiating; magnesium particularly useful during pregnancy 2, 4

Sequential Monotherapy Approach

• Try sequential monotherapies before combination therapy 5
• If sequential monotherapies fail, try combinations of first-line drugs before advancing to second-choice drugs 4