What medication options are available to treat migraines in a patient with potential cardiovascular disease history and frequent or severe episodes?

Migraine Treatment: Medication Options

First-Line Treatment for Mild to Moderate Migraine

Start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg as first-line therapy for mild to moderate migraine attacks. 1 These medications have demonstrated strong efficacy, favorable tolerability, and lower cost compared to prescription alternatives. 1, 2

• Naproxen sodium 500-825 mg at migraine onset is particularly effective, with the option to repeat every 2-6 hours as needed (maximum 1.5 g/day). 3
• Combination therapy with acetaminophen, aspirin, and caffeine provides synergistic analgesia and is recommended when patients respond poorly to NSAIDs alone. 3
• Critical limitation: Restrict NSAID use to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 3

Escalation to Triptans for Moderate to Severe Migraine

If NSAIDs or acetaminophen fail after 2-3 migraine episodes, add a triptan to the NSAID regimen—this combination is superior to either agent alone and represents the strongest evidence-based recommendation. 1, 3 The combination provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy. 3

Triptan Selection and Dosing:

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is the preferred oral combination for moderate to severe attacks. 3
• Alternative triptans include rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60-90 minutes), eletriptan 40 mg, or zolmitriptan 2.5-5 mg. 3
• If one triptan fails after 2-3 headache episodes, try a different triptan—failure of one does not predict failure of others. 3
• For rapid progression or severe nausea/vomiting, subcutaneous sumatriptan 6 mg provides the highest efficacy with onset within 15 minutes (59% complete pain relief by 2 hours). 3, 4

Critical Cardiovascular Contraindications:

Triptans are absolutely contraindicated in patients with ischemic heart disease, previous myocardial infarction, uncontrolled hypertension, cerebrovascular disease (stroke/TIA), peripheral vascular disease, or Prinzmetal's angina. 5, 6, 5 For patients with multiple cardiovascular risk factors (age >40 in men, postmenopausal women, diabetes, hypertension, smoking, obesity, strong family history of CAD), perform cardiovascular evaluation before prescribing triptans and consider administering the first dose in a medically supervised setting. 5, 6

Alternative Options When Triptans Are Contraindicated or Ineffective

For patients who cannot tolerate or have inadequate response to triptan-NSAID combination therapy, consider CGRP antagonists (gepants: ubrogepant 50-100 mg, rimegepant, or zavegepant) as the primary alternative. 1, 3 These agents have no vasoconstriction, making them safe for patients with cardiovascular disease. 3

• Lasmiditan (ditan) 50-200 mg is a second-line alternative when gepants are unavailable or ineffective, but patients must not drive or operate machinery for at least 8 hours due to CNS effects. 1, 3
• Dihydroergotamine (intranasal or IV) has good evidence for efficacy as monotherapy for acute attacks. 1, 3

Adjunctive Antiemetic Therapy

Add metoclopramide 10 mg IV or prochlorperazine 10 mg IV for migraine-associated nausea—these provide direct analgesic effects through central dopamine receptor antagonism, not just antiemetic benefit. 3 Metoclopramide also enhances absorption of co-administered medications by overcoming gastric stasis. 3

IV Treatment for Severe Refractory Migraine

For severe attacks requiring emergency treatment, use metoclopramide 10 mg IV PLUS ketorolac 30 mg IV as first-line combination therapy. 3 Ketorolac provides rapid onset with approximately 6 hours duration and minimal rebound headache risk. 3

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine) or butalbital-containing compounds for migraine treatment—these lead to dependency, rebound headaches, medication-overuse headache, and eventual loss of efficacy. 1, 3 Reserve opioids only for cases where all other medications are contraindicated, sedation is not a concern, and abuse risk has been addressed. 3

Critical Frequency Limitation Across All Acute Medications

Limit all acute migraine medications to no more than 2 days per week (10 days per month for triptans, 15 days per month for NSAIDs/acetaminophen) to prevent medication-overuse headache. 1, 3 If patients require acute treatment more frequently, initiate preventive therapy immediately with propranolol 80-240 mg/day, topiramate, or amitriptyline 30-150 mg/day. 3, 7

Special Considerations for Pregnancy

Acetaminophen 1000 mg is the only first-line medication for acute migraine treatment during pregnancy. 8 NSAIDs can be used only during the second trimester. 8 Metoclopramide is safe for migraine-associated nausea, particularly in the second and third trimesters. 8 Absolutely avoid triptans, ergotamines, opioids, butalbital, topiramate, valproate, and gepants during pregnancy due to fetal risks. 8