What medications are recommended for a patient with migraine headaches, considering their medical history and potential cardiovascular disease?

Medications for Migraine Headaches

First-Line Treatment: Start with NSAIDs or Acetaminophen

For mild to moderate migraine attacks, begin with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg as first-line therapy. 1

• These medications have strong evidence for efficacy and should be taken at the earliest signs of headache onset 1
• Ensure adequate dosing before declaring treatment failure—many patients use subtherapeutic doses 1
• If NSAIDs are contraindicated (renal impairment, GI bleeding history, aspirin-induced asthma), use acetaminophen instead 1

Second-Line: Add a Triptan for Moderate to Severe Attacks

If NSAIDs or acetaminophen at adequate doses fail to provide sufficient relief, add a triptan to the NSAID (or to acetaminophen when NSAIDs are contraindicated). 1

• The combination of triptan + NSAID is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours 1
• Available triptans include almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan 1
• Failure of one triptan does not predict failure of others—try a different triptan if the first is ineffective 1
• For severe nausea or vomiting, consider non-oral triptan formulations (subcutaneous sumatriptan 6 mg provides the highest efficacy with onset within 15 minutes) 1

Critical Cardiovascular Considerations for Triptans

Triptans are absolutely contraindicated in patients with established cardiovascular disease, including coronary artery disease, previous myocardial infarction, Prinzmetal's angina, uncontrolled hypertension, stroke, or TIA. 2

• For triptan-naive patients with multiple cardiovascular risk factors (increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), perform a cardiovascular evaluation before prescribing triptans 2
• If cardiovascular evaluation is negative but multiple risk factors exist, consider administering the first dose in a medically supervised setting with ECG monitoring 2
• Life-threatening cardiac arrhythmias, including ventricular tachycardia and ventricular fibrillation, have been reported with triptan use 2
• Triptans are contraindicated in Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders 2

Third-Line: CGRP Antagonists (Gepants) for Cardiovascular Disease

For patients with cardiovascular disease or contraindications to triptans who do not respond to NSAIDs/acetaminophen alone, use CGRP antagonists (rimegepant, ubrogepant, or zavegepant). 1

• Gepants have no vasoconstrictor activity, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 1
• These agents should be considered when combination therapy of triptan + NSAID is contraindicated or has failed 1

Fourth-Line: Dihydroergotamine or Lasmiditan

Consider dihydroergotamine (DHE) or lasmiditan for patients who do not tolerate or have inadequate response to all previous options. 1

• DHE has good evidence for efficacy and safety as monotherapy 1
• Lasmiditan is reserved for patients who do not tolerate or have inadequate response to all other pharmacologic treatments in this guideline 1
• Lasmiditan causes CNS effects (dizziness, somnolence); patients must not drive or operate machinery for at least 8 hours after taking it 3

Adjunctive Antiemetic Therapy

Add an antiemetic (metoclopramide 10 mg IV or prochlorperazine 10 mg IV) for patients with severe nausea or vomiting. 1

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, beyond its antiemetic properties 1
• Consider non-oral triptan formulations when significant nausea or vomiting is present 1

Medications to Absolutely Avoid

Do not use opioids or butalbital-containing compounds for acute episodic migraine treatment. 1

• These medications have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1
• Opioids should only be reserved for cases where all other medications cannot be used, when sedation is not a concern, and when abuse risk has been addressed 1

Critical Frequency Limitation: Preventing Medication-Overuse Headache

Strictly limit all acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache. 1

• Medication-overuse headache is defined as headache occurring on ≥15 days per month for at least 3 months in people with a preexisting headache disorder 1
• The threshold varies by treatment: ≥15 days per month with NSAIDs; ≥10 days per month with triptans 1
• If patients require acute treatment more than twice weekly, initiate preventive therapy immediately 1

When to Initiate Preventive Therapy

Add preventive medications if episodic migraine occurs frequently (≥2 attacks per month with disability lasting ≥3 days) or if acute treatment does not provide adequate response. 1, 4

• First-line preventive options include propranolol 80-240 mg/day, timolol 20-30 mg/day, topiramate 100 mg/day, or candesartan 4
• Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments 4
• Allow an adequate trial period of 2-3 months before assessing efficacy of oral preventive agents 4

Special Populations

In patients of childbearing potential, pregnant, or breastfeeding women, discuss adverse effects of pharmacologic treatments during pregnancy and lactation before initiating therapy. 1

• Acetaminophen remains the first choice for pregnant women 5
• Valproate is strictly contraindicated in women of childbearing potential due to teratogenic effects 4

Common Pitfalls to Avoid

• Failing to ensure adequate dosing before declaring treatment failure—many patients use subtherapeutic doses of NSAIDs or acetaminophen 1
• Not recognizing medication-overuse headache from frequent use of acute medications (≥10 days/month for triptans, ≥15 days/month for NSAIDs) 1, 2, 3
• Prescribing triptans without cardiovascular screening in patients with multiple cardiovascular risk factors 2
• Using opioids or butalbital as routine therapy, which leads to dependency and medication-overuse headache 1
• Delaying preventive therapy in patients requiring acute treatment more than twice weekly 1, 4