What alternative medications are available for treating intractable migraines?

From the Guidelines

For intractable migraines, CGRP antagonists such as erenumab, fremanezumab, or galcanezumab are recommended as preventive treatments, while eletriptan, frovatriptan, rizatriptan, sumatriptan, or zolmitriptan are recommended for acute treatment. When considering alternative medications for intractable migraines, several options are available.

• Preventive treatments include:
  • CGRP antagonists: erenumab (Aimovig, 70-140 mg monthly), fremanezumab (Ajovy, 225 mg monthly), and galcanezumab (Emgality, 120 mg monthly) as per 1
  • Anti-seizure medications: topiramate (50-200 mg daily) and valproate (500-1500 mg daily)
  • Beta-blockers: propranolol (40-240 mg daily) and metoprolol (50-200 mg daily)
• Acute treatments include:
  • Triptans: eletriptan, frovatriptan, rizatriptan, sumatriptan (oral or subcutaneous), or zolmitriptan (oral or intranasal) as per 1
  • Ergot alkaloids: dihydroergotamine (DHE) nasal spray or injection
  • CGRP antagonists-gepants: rimegepant, ubrogepant, or zavegepant as per 1 It is essential to individualize treatment selection based on comorbidities, side effect profiles, and previous medication responses, and patients should maintain a headache diary to track effectiveness. Additionally, patients should be aware of medication overuse headache, which is a potential complication of migraine treatment, as noted in 1. Non-pharmacological alternatives, such as neuromodulation devices, may also be considered for some patients. The choice of a specific medication should be based on individualized decision making, taking into consideration patient preferences on such factors as route of administration and cost, as per 1.

From the Research

Alternative Medications for Intractable Migraines

• The following medications have been studied for the treatment of intractable migraines:
  • Naratriptan: A study published in 2003 found that naratriptan 2.5 mg twice daily was effective in treating intractable migraine attacks, with 79% of patients showing improvement 2
  • OnabotulinumtoxinA (BOTOX): Studies have shown that onabotulinumtoxinA is effective in reducing the frequency and severity of headaches in patients with chronic migraine, with long-term safety data available 3, 4
  • Topiramate: While topiramate has been shown to be effective in reducing headache frequency, it has been found to have a higher discontinuation rate due to adverse events compared to onabotulinumtoxinA 4
  • CGRP monoclonal antibodies (erenumab, galcanezumab, and fremanezumab): These medications have been found to be effective in reducing headache frequency, but long-term safety data is limited 3
• Other medications that have been studied for migraine prevention include:
  • Beta-blockers (propranolol, timolol, atenolol, metoprolol, nadolol) 5, 6
  • Anticonvulsants (valproate, divalproex, topiramate, gabapentin) 5, 6
  • Antidepressants (amitriptyline, fluoxetine, venlafaxine) 5, 6
  • Botulinum toxin type A 5, 6
  • Butterbur root, riboflavin, and magnesium 6

Mechanisms of Action

• The exact mechanisms of action of these medications in treating intractable migraines are not fully understood, but they are thought to involve:
  • Inhibition of pain pathways
  • Reduction of inflammation
  • Modulation of neurotransmitter activity
  • Blockage of CGRP receptors

Efficacy and Safety

• The efficacy and safety of these medications vary, with some having more robust evidence to support their use than others
• OnabotulinumtoxinA has been found to have a favorable safety profile and long-term efficacy in reducing headache frequency 3, 4
• Topiramate has been found to have a higher discontinuation rate due to adverse events compared to onabotulinumtoxinA 4
• CGRP monoclonal antibodies have been found to be effective, but long-term safety data is limited 3