What are the next steps for patients under 40 with migraines that do not respond to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), antiemetics, and triptans?

Management of Migraines Not Responding to NSAIDs, Antiemetics, and Triptans in Patients Under 40

For patients under 40 with migraines that do not respond to NSAIDs, antiemetics, and triptans, the next step should be to initiate preventive therapy with either propranolol (80-240 mg/day), timolol (20-30 mg/day), amitriptyline (30-150 mg/day), divalproex sodium (500-1500 mg/day), or sodium valproate (800-1500 mg/day) as first-line preventive agents. 1

Evaluation for Secondary Causes

• Before initiating new treatments, evaluate for potential secondary headache causes, especially when standard treatments fail, looking for red flags such as:
  • Thunderclap headache (suggesting subarachnoid hemorrhage)
  • Atypical aura (suggesting TIA, stroke, epilepsy)
  • Progressive headache pattern (suggesting intracranial space-occupying lesion)
  • Headache aggravated by postures that raise intracranial pressure 1

Third-Line Acute Treatment Options

• Consider CGRP antagonists (gepants) such as rimegepant, ubrogepant, or zavegepant as third-line acute treatment options for patients who don't respond to NSAIDs and triptans 2, 3
• Dihydroergotamine (DHE), particularly in intranasal formulation, can be effective for patients with triptan failure 2, 3
• Lasmiditan (ditan) may be considered for moderate to severe migraine when other options have failed, though its use is associated with temporary driving impairment 1, 3

Preventive Treatment Indications

• Preventive therapy should be initiated when:
  • Patient experiences two or more attacks per month with disability lasting 3 or more days
  • Acute treatments have failed or are contraindicated
  • Abortive medications are used more than twice per week
  • Uncommon migraine conditions are present (hemiplegic migraine, migraine with prolonged aura) 1

First-Line Preventive Options

• Beta-blockers:
  • Propranolol (80-240 mg/day) or timolol (20-30 mg/day) are effective first-line preventive agents 1
• Antidepressants:
  • Amitriptyline (30-150 mg/day) is effective for migraine prevention 1
• Anticonvulsants:
  • Divalproex sodium (500-1500 mg/day) or sodium valproate (800-1500 mg/day) have proven efficacy 1

Important Considerations

• Preventive medications require 2-3 months at therapeutic doses to determine efficacy, so encourage patients to continue treatment during this evaluation period 1
• Start with low doses and titrate slowly to achieve clinical benefits while minimizing adverse events 1
• Monitor for medication overuse headache, which can occur with frequent use of acute medications (≥15 days per month with most medications; ≥10 days per month with triptans) 2, 3
• Avoid oral ergot alkaloids, opioids, and barbiturates due to questionable efficacy, adverse effects, and risk of dependency 1, 2

Treatment Algorithm for Refractory Migraine

1. Rule out secondary headache disorders using appropriate imaging and diagnostic tests 1
2. Initiate preventive therapy with one of the first-line agents 1
3. For breakthrough attacks, consider third-line acute treatments (CGRP antagonists, DHE, or lasmiditan) 2, 3
4. For status migrainosus (severe, continuous migraine lasting up to one week), systemic steroids may be appropriate 2
5. If first-line preventive therapy fails after 2-3 months, switch to an alternative first-line agent from a different medication class 1

Pitfalls to Avoid

• Avoid overuse of acute medications, which can lead to medication overuse headache and decreased efficacy of preventive treatments 1, 2
• Do not abandon preventive treatments prematurely; efficacy may take 2-3 months to manifest 1
• Avoid opioids and butalbital-containing medications for routine migraine treatment due to risks of dependency and rebound headaches 2, 3
• Don't neglect to address comorbid conditions that may exacerbate migraines, such as depression, anxiety, or sleep disorders 1