What is the treatment for a complex migraine?

Treatment of Complex Migraine

For complex migraine (migraine with aura or neurological symptoms), use a stepped-care approach starting with NSAIDs for mild-to-moderate attacks, escalating to triptans for moderate-to-severe attacks, but exercise extreme caution with triptans in patients with aura due to increased stroke risk, and consider ditans or gepants as safer third-line alternatives. 1

Critical Safety Consideration for Complex Migraine

• Avoid vasoactive medications (triptans and ergots) in patients with migrainous infarction or prolonged aura lasting >60 minutes, as these patients have higher stroke risk. 2
• Migraine with aura is associated with increased risk of ischemic stroke, particularly in younger women, those using oral contraceptives, and smokers. 2, 3
• Triptans should be used with extreme caution in patients with cardiovascular risk factors or history of stroke. 1

Acute Treatment Algorithm

First-Line: NSAIDs (Mild-to-Moderate Attacks)

• Ibuprofen 400-800 mg every 6 hours 1
• Naproxen sodium 550 mg at onset, repeat every 2-6 hours as needed (maximum 1.5 g/day) 1
• Aspirin 650-1000 mg every 4-6 hours 1
• Combination analgesics containing acetaminophen, aspirin, and caffeine are effective alternatives. 1
• Take medication early when pain is still mild to maximize efficacy. 4

Second-Line: Triptans (Moderate-to-Severe Attacks)

• Sumatriptan 100 mg orally (bioavailability 15%, Cmax 51 ng/mL, Tmax 2-2.5 hours) 5
• Alternative triptans if sumatriptan fails: rizatriptan 10 mg, naratriptan 2.5 mg, or zolmitriptan 2.5-5 mg 4
• For rapid onset or severe nausea/vomiting: subcutaneous sumatriptan 6 mg (Cmax 71 ng/mL, highest efficacy with 59% complete pain relief at 2 hours) 6
• Intranasal sumatriptan 5-20 mg for patients unable to tolerate oral medication 6
• Triptans work via 5-HT1B/1D receptor agonism, causing cranial vessel constriction and inhibiting pro-inflammatory neuropeptide release. 5

Third-Line: Ditans or Gepants (Failed Triptan Therapy or Contraindications)

• Lasmiditan (selective 5HT1F receptor agonist) - safer cardiovascular profile than triptans 7
• Gepants (CGRP receptor antagonists): rimegepant, ubrogepant, or zavegepant 6, 7
• These agents avoid vasoconstriction, making them safer for patients with cardiovascular risk factors or stroke history. 7

Adjunctive Therapy for Nausea/Vomiting

• Metoclopramide 10 mg IV/PO - provides direct analgesic effects through dopamine receptor antagonism plus prokinetic effects 6
• Prochlorperazine 10 mg IV/PO - comparable efficacy to metoclopramide with 21% adverse event rate 6
• Antiemetics provide synergistic analgesia when combined with NSAIDs or triptans. 4

Emergency Department/Urgent Care IV Treatment

• First-line IV combination: Metoclopramide 10 mg IV + Ketorolac 30 mg IV 6
• Ketorolac has rapid onset with 6-hour duration and minimal rebound headache risk. 6
• Alternative: Prochlorperazine 10 mg IV + Ketorolac 30 mg IV 6
• Dihydroergotamine (DHE) IV for refractory cases, but contraindicated in patients with cardiovascular disease or recent triptan use 6, 8

Preventive Treatment (When Attacks Occur >2 Days/Week)

• First-line: Topiramate (preferred for chronic migraine due to lower cost) 1
• Alternative first-line: Valproic acid (contraindicated in women of childbearing potential) 4
• Second-line: CGRP monoclonal antibodies (requires 3-6 months for full efficacy) 6, 7
• OnabotulinumtoxinA for chronic migraine after failed oral preventives (requires 6-9 months for efficacy) 1, 6
• Preventive therapy requires 2-3 months for oral agents to demonstrate full efficacy. 4

Critical Pitfalls to Avoid

• Never allow acute medication use >2 days per week - this causes medication-overuse headache and transforms episodic migraine to chronic daily headache. 1, 4, 6
• Avoid opioids and barbiturates - they cause dependency, rebound headaches, and have limited efficacy evidence. 1
• Do not increase acute medication frequency when treatment fails - instead, escalate to preventive therapy. 6
• Screen for and modify stroke risk factors - hypertension, smoking, oral contraceptive use, especially in patients with aura. 2, 3

When to Escalate Treatment

• If NSAIDs fail after 2-3 attacks, switch to triptans. 6
• If one triptan fails, try a different triptan before abandoning the class. 6
• If all triptans fail after adequate trials, escalate to ditans or gepants. 1
• If headaches occur >2 days/week or cause significant disability, initiate preventive therapy. 4

Managing Comorbidities

• Identify and treat depression, sleep disturbances, obesity, and cardiovascular risk factors. 1
• Consider amitriptyline for patients with comorbid depression and migraine. 1
• Topiramate provides dual benefit for migraine prevention and weight management. 1