What are the treatment options for migraine headaches?

Migraine Headache Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with combination therapy of an NSAID plus acetaminophen, or the fixed-dose combination of acetaminophen/aspirin/caffeine as first-line treatment. 1

Mild to Moderate Attacks

• Begin treatment immediately upon headache onset with combination therapy of an NSAID (aspirin, ibuprofen, naproxen, or diclofenac) plus acetaminophen for optimal efficacy. 1, 2
• The fixed-dose combination of acetaminophen/aspirin/caffeine is equally effective as first-line therapy. 1
• Acetaminophen 1000 mg monotherapy can be used but is significantly less effective than NSAIDs or combination therapy. 1
• Early administration is critical—treating while pain is still mild substantially improves treatment success rates. 1, 2

Moderate to Severe Attacks

• Escalate to triptan plus NSAID combination therapy for moderate to severe attacks or when simple analgesics fail. 2, 3
• Combining a triptan with an NSAID or acetaminophen provides superior efficacy compared to either agent alone. 2, 3
• If one triptan fails, trial a different triptan as individual response varies significantly. 2
• For patients with severe nausea/vomiting, use non-oral routes: subcutaneous sumatriptan injection, intranasal formulations, or rectal suppositories. 2, 4

Refractory Cases

• For patients who fail all available triptans or have contraindications (cardiovascular disease, uncontrolled hypertension, hemiplegic migraine), escalate to CGRP antagonists (rimegepant, ubrogepant, zavegepant), dihydroergotamine, or lasmiditan. 1, 2
• Lasmiditan should only be considered after failure of all other pharmacologic treatments. 1

Emergency Department Management

• For severe migraine requiring parenteral therapy, use IV ketorolac 30 mg plus IV metoclopramide 10 mg as first-line combination therapy. 1
• IV antiemetics (metoclopramide or prochlorperazine) treat nausea while improving gastric motility and medication absorption. 2
• Consider adding dexamethasone to prevent short-term headache recurrence. 5

Critical Medication Overuse Prevention

• Limit NSAID use to ≤15 days per month to prevent medication overuse headache. 1, 2, 3
• Limit triptan use to ≤10 days per month to prevent medication overuse headache. 1, 2, 3
• Initiate preventive therapy if acute treatment is needed more than 2 days per week (≥8-10 days per month). 1, 2
• Avoid opioids and butalbital-containing analgesics entirely—these medications worsen migraine outcomes and increase medication overuse headache risk. 2

Preventive Therapy Indications

Consider preventive therapy when patients have ≥2 migraine attacks per month producing disability, contraindications to acute treatments, or frequent acute medication use. 2, 3

First-Line Preventive Medications

• Topiramate is recommended as first-choice preventive therapy due to lower cost, but requires counseling about teratogenic effects in patients of childbearing potential. 2, 3
• Propranolol or metoprolol (beta-blockers) are effective first-line options. 6
• Divalproex or valproate are effective but also require teratogenicity counseling. 6
• CGRP receptor antagonists (erenumab, fremanezumab, galcanezumab) are highly effective but limited by cost and insurance coverage. 6

Second-Line Options

• Consider ACE inhibitors, ARBs, or SSRIs if first-line treatments are not tolerated or provide inadequate response. 2
• Amitriptyline and venlafaxine are second-line due to more adverse events. 6

Chronic Migraine (≥15 Headache Days/Month)

• OnabotulinumtoxinA 155 units is FDA-approved and specifically indicated for chronic migraine, with evidence from large-scale placebo-controlled trials showing effectiveness. 2
• Rule out secondary causes before establishing chronic migraine diagnosis. 2
• Monitor closely for medication overuse headache and limit as-needed medication use. 2

Essential Lifestyle Modifications

• Counsel all patients on: adequate hydration, regular meal schedule, consistent sleep (7-8 hours nightly), regular moderate-to-intense aerobic exercise (40 minutes three times weekly), and stress management techniques. 1, 2, 3
• Regular aerobic exercise is as effective as some preventive medications. 2
• Recommend weight loss if overweight or obese, as obesity increases chronic migraine risk. 1, 3
• Encourage patients to maintain a headache diary to identify triggers, monitor treatment efficacy, and detect analgesic overuse. 2, 3

Non-Pharmacologic Therapies

• Offer cognitive-behavioral therapy, biofeedback, and relaxation training to all patients as these have good evidence for efficacy and should be part of comprehensive management. 2

Special Populations

Pregnancy and Lactation

• Acetaminophen is first-line treatment for pregnant or breastfeeding patients. 1
• NSAIDs are acceptable prior to the third trimester but must be avoided in the third trimester. 1
• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation before prescribing. 3

Pediatric Patients

• Acetaminophen, ibuprofen, intranasal sumatriptan, and intranasal zolmitriptan appear effective in children and adolescents, though data are limited. 5
• Oral eletriptan 40 mg was not effective in adolescents aged 11-17 in controlled trials. 4

Elderly Patients

• Blood pressure increases are more pronounced in elderly patients treated with triptans; monitor blood pressure closely. 4
• Pharmacokinetics are similar to younger adults, though elimination half-life may be slightly prolonged. 4

Cost Considerations

• Prescribe generic NSAIDs and older triptans (sumatriptan, naratriptan, rizatriptan) when equally effective, as these are significantly less expensive than newer agents. 1, 3

Critical Safety Warnings for Triptans

• Contraindicated in patients with: coronary artery disease, Prinzmetal's angina, uncontrolled hypertension, history of stroke or TIA, hemiplegic migraine, Wolff-Parkinson-White syndrome, or peripheral vascular disease. 4
• Discontinue immediately if chest pain, arrhythmias, or signs of vasospastic reactions occur. 4
• Monitor for serotonin syndrome when co-administering with SSRIs, SNRIs, TCAs, or MAO inhibitors. 4
• Avoid in patients taking strong CYP3A4 inhibitors due to increased eletriptan levels. 4