What are the treatment options for intractable (unmanageable) migraine headaches?

From the Guidelines

Intractable migraines can be effectively managed with CGRP antagonists, such as rimegepant, ubrogepant, or zavegepant, or the ditan lasmiditan, as these options have shown efficacy in treating moderate to severe acute episodic migraine headache in nonpregnant outpatient adults who do not tolerate or have inadequate response to combination therapy of a triptan and an NSAID or acetaminophen 1. When considering treatment options for intractable migraines, it is essential to prioritize individualized decision making, taking into account patient preferences and factors such as route of administration and cost.

• For mild episodic migraine headache, consider treating with an NSAID, acetaminophen, or the combination of an NSAID and acetaminophen 1.
• For moderate to severe acute episodic migraine headache, consider using CGRP antagonists or ergot alkaloid (dihydroergotamine) in nonpregnant outpatient adults who do not tolerate or have inadequate response to combination therapy of a triptan and an NSAID or acetaminophen 1.
• The ditan lasmiditan can be considered for moderate to severe acute episodic migraine headache in nonpregnant outpatient adults who do not tolerate or have inadequate response to all other pharmacologic treatments included in the guideline 1. It is crucial to avoid using opioids or butalbital for the treatment of acute episodic migraine, as they can lead to medication overuse headache 1.
• Nonoral triptans and antiemetics can be used in people having severe nausea or vomiting 1.
• Patients should be counseled to begin treatment of migraine headache as soon as possible after its onset, using combination therapy to improve efficacy 1.
• If the episodic migraine occurs frequently or treatment does not provide an adequate response, the addition of preventive medications may be warranted 1.
• Preventive treatment options, such as beta blockers, topiramate, or candesartan, can be considered for patients who are adversely affected by migraine on ≥2 days per month despite optimized acute treatment 1.

From the FDA Drug Label

Sumatriptan tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. The use of sumatriptan tablets is contraindicated in patients with CAD and those with Prinzmetal’s variant angina. Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities Sumatriptan tablets are contraindicated in patients with a history of stroke or TIA. Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Options to treat intractable migraine include:

• Sumatriptan (PO): can be used to treat migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system. However, caution is advised due to potential risks of:
  • Cerebrovascular events
  • Cardiac complications
  • Serotonin syndrome
  • Increased blood pressure
  • Anaphylactic reactions
  • Seizures It is essential to carefully evaluate the patient's medical history and current condition before administering sumatriptan 2 2.

From the Research

Treatment Options for Intractable Migraine

• Pharmacological therapies:
  • Beta-blockers, flunarizine, topiramate, valproate, and amitriptyline are considered first-line treatments for migraine prophylaxis 3
  • Venlafaxine, gabapentin, naproxen, butterbur root, riboflavin, and magnesium are considered second-line treatments due to less efficacy and evidence 3
  • Anti-epileptic drugs such as topiramate and valproate are effective for preventive treatment of migraine, while others like gabapentin or lamotrigine may have a role in specific cases 4
• Non-pharmacological therapies:
  • Relaxation techniques, bio-feedback, cognitive behavioral therapy, and acupuncture are supported by some evidence, but require specialist time or technical devices 3
  • Neuromodulation and biobehavioural approaches can be used for a multidisciplinary approach to clinical management 5
• Inpatient treatment:
  • Comprehensive inpatient programs have shown significant improvement in reducing headache frequency and severity, as well as improving functional performance and work status 6
  • Treatment of status migrainosus and intractable migraine in an inpatient setting should focus on adequate fluid hydration and combination IV therapy with multiple nonopioid medications from multiple drug classes 7

Emerging Treatments

• Novel mechanism-based medications have emerged, expanding the armamentarium of treatments for migraine 5
• Emerging mechanism-based treatments may address unmet challenges in clinical management of migraine, but more research is needed to determine their efficacy and safety 5