What are alternative treatment options for migraine prophylaxis in the absence of Calcitonin Gene-Related Peptide (CGRP) inhibitors?

From the Guidelines

Alternative treatments for migraine prophylaxis should prioritize beta-blockers, antiepileptic drugs, and tricyclic antidepressants when CGRP inhibitors are not available. Several effective options exist for migraine prophylaxis in the absence of Calcitonin Gene-Related Peptide (CGRP) inhibitors, as outlined in the clinical guideline from the American College of Physicians 1.

First-line Treatment Options

• Beta-blockers such as propranolol (40-240 mg daily) and metoprolol (50-200 mg daily) are recommended as first-line treatments due to their efficacy in reducing migraine frequency by modulating vascular tone and neural excitability.
• Antiepileptic drugs like topiramate (25-100 mg twice daily) and valproate (500-1000 mg daily) are also effective by stabilizing neuronal membranes and reducing cortical spreading depression.

Additional Treatment Options

• Tricyclic antidepressants, particularly amitriptyline (10-150 mg at bedtime), can be used as they work by increasing serotonin and norepinephrine levels.
• Calcium channel blockers such as flunarizine (5-10 mg daily) can help by inhibiting calcium influx and reducing neuronal excitability.
• For patients with comorbid hypertension, angiotensin receptor blockers like candesartan (16-32 mg daily) offer dual benefits.
• Botulinum toxin A injections (155-195 units every 12 weeks) are effective for chronic migraine by blocking pain neurotransmitter release.

Non-Pharmacological Approaches

• Regular aerobic exercise, consistent sleep schedules, stress management techniques, and trigger avoidance should complement medication therapy. Treatment selection should be individualized based on comorbidities, side effect profiles, and patient preferences, with regular follow-up to assess efficacy and tolerability, as suggested by the American College of Physicians guideline 1.

From the Research

Alternative Treatment Options for Migraine Prophylaxis

In the absence of Calcitonin Gene-Related Peptide (CGRP) inhibitors, several alternative treatment options are available for migraine prophylaxis. These options include:

• First-line agents:
  • Beta-blockers (e.g., propranolol, timolol) 2, 3, 4, 5
  • Amitriptyline 2, 3, 4, 5
  • Valproate (sodium valproate, divalproex) 2, 3, 4, 6, 5
  • Topiramate 2, 3, 4, 6, 5
  • Flunarizine 2, 4, 5
• Second-line agents:
  • Gabapentin 3, 4, 6, 5
  • Naproxen sodium 3, 4, 5
  • Venlafaxine 4, 5
  • Butterbur root 4, 5
  • Vitamin B2 (riboflavin) 4, 5
  • Magnesium 4, 5
• Other options:
  • Botulinum toxin type A 3
  • Aspirin 2
  • DHE 2
  • Indoramine 2
  • Angiotensin II inhibitors 2
  • Oxetorone 2
  • Pizotifene 2
  • Methysergide 2
  • NSAIDs 2

Considerations for Treatment Selection

The choice of prophylactic drug depends on various factors, including:

• Efficacy
• Co-morbidity
• Side effects
• Availability
• Cost
• Patient characteristics and preferences 2, 3, 4, 5

Non-Pharmacological Treatments

Non-pharmacological treatments, such as relaxation techniques, bio-feedback, cognitive behavioral therapy, and acupuncture, may also be considered for migraine prophylaxis, although they require more specialist time or technical devices 4.