What are the recommended acute and preventive treatment options for a typical adult with migraine headaches?

Migraine Headache Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg) or the combination of acetaminophen 1000 mg + aspirin 500-1000 mg + caffeine 130 mg as first-line therapy. 1, 2

For moderate to severe migraine or when NSAIDs fail after 2-3 episodes, immediately escalate to combination therapy with a triptan PLUS an NSAID—this provides 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to either agent alone. 1, 2

First-Line Acute Treatment Strategy

• Mild to moderate attacks: Begin with NSAIDs alone—ibuprofen 400-800 mg, naproxen sodium 500-825 mg, aspirin 1000 mg, or diclofenac potassium. 1, 3, 4
• Alternatively, use the fixed combination of acetaminophen 1000 mg + aspirin 500-1000 mg + caffeine 130 mg, which achieves pain reduction to mild or none in 59.3% of patients at 2 hours. 1
• Acetaminophen 1000 mg can be used as monotherapy but is less effective than NSAIDs or combination therapy. 2

Second-Line: Triptan + NSAID Combination

• When NSAIDs fail or for moderate to severe attacks from the outset, use sumatriptan 50-100 mg PLUS naproxen sodium 500 mg. 1, 2
• This combination is superior to either agent alone with a number-needed-to-treat of 3.5 for headache relief at 2 hours. 1
• Alternative oral triptans with strong evidence include rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60-90 minutes), eletriptan 40 mg, zolmitriptan 2.5-5 mg, almotriptan, frovatriptan, and naratriptan. 1, 3, 4
• If one triptan fails after 2-3 headache episodes, switch to a different triptan—failure of one does not predict failure of others. 1

Non-Oral Routes for Severe Nausea/Vomiting

• Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, achieving complete pain relief in 59% of patients within 2 hours and onset of action within 15 minutes. 1
• Intranasal sumatriptan 5-20 mg or other nasal spray triptans are particularly useful when significant nausea or vomiting is present. 1, 3

Third-Line: CGRP Antagonists (Gepants)

• Ubrogepant 50-100 mg or rimegepant are recommended only after failure of triptan + NSAID combination therapy. 1, 2
• Gepants have no vasoconstriction, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease. 1
• Limit ubrogepant use to no more than 8 migraine attacks per 30-day period to prevent medication overuse headache. 1

Parenteral Therapy for Emergency/Urgent Care

• IV metoclopramide 10 mg plus IV ketorolac 30 mg is first-line combination therapy for severe migraine requiring intravenous treatment. 1, 2
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic benefit. 1
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk. 1
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy. 1
• Dihydroergotamine (DHE) 0.5-1.0 mg IV has good evidence for efficacy as monotherapy, can be repeated every hour up to 2 mg IV per day. 1

Adjunctive Antiemetic Therapy

• Add metoclopramide 10 mg or prochlorperazine 25 mg orally 20-30 minutes before NSAIDs or triptans to provide synergistic analgesia and improve outcomes. 1
• Prokinetic antiemetics overcome gastric stasis during migraine attacks, enhancing absorption of co-administered medications. 1, 5

Critical Medication Frequency Limits

Limit ALL acute migraine medications to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2

• Triptans, ergots, and combination analgesics trigger medication-overuse headache at ≥10 days per month. 1
• NSAIDs and acetaminophen trigger medication-overuse headache at ≥15 days per month. 1
• If acute treatment is needed more than twice weekly, immediately initiate preventive therapy rather than increasing frequency of acute medications. 1, 2

Timing of Treatment

Treat migraine early when pain is still mild—approximately 50% of patients become pain-free at 2 hours versus only 28% when treatment is delayed until pain is moderate or severe. 1

Preventive Therapy Indications

Initiate preventive therapy when any of the following criteria are met: 1, 2, 6

• ≥2 migraine attacks per month producing disability lasting ≥3 days
• Use of acute medication more than 2 days per week
• Contraindication to or failure of acute treatments
• Special circumstances such as hemiplegic migraine
• Patient preference for preventive approach

First-Line Preventive Medications

• Beta-blockers without intrinsic sympathomimetic activity: propranolol 80-240 mg/day or timolol 20-30 mg/day have the strongest evidence. 1, 6
• Topiramate and divalproex sodium/sodium valproate are also first-line options, though valproate is strictly contraindicated in women of childbearing potential due to teratogenic risk. 1, 6
• Amitriptyline 30-150 mg/day is preferred for patients with comorbid depression, anxiety, sleep disturbances, or mixed migraine and tension-type headache. 1, 6

Third-Line Preventive Options

• CGRP monoclonal antibodies (erenumab, fremanezumab) or onabotulinumtoxinA (Botox) 155-195 U every 12 weeks are recommended when first-line oral preventives have failed or for chronic migraine (≥15 headache days per month). 1
• OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine. 1
• Efficacy requires 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA. 1

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine, oxycodone, codeine) or butalbital-containing compounds for routine migraine treatment—they have questionable efficacy, lead to dependency, cause rebound headaches, result in loss of efficacy over time, and carry a two-fold higher risk of medication-overuse headache compared to NSAIDs and triptans. 1, 5, 2

• Reserve opioids exclusively for cases where every other evidence-based treatment is contraindicated, sedation is acceptable, and formal assessment of abuse risk has been completed. 1
• If an opioid must be used, butorphanol nasal spray has better evidence than other opioids specifically for headache treatment. 1

Contraindications to Triptans

• Ischemic heart disease, previous myocardial infarction, coronary artery vasospasm 1
• Uncontrolled hypertension 1
• Cerebrovascular disease, history of stroke or TIA 1
• Basilar or hemiplegic migraine 1
• Significant cardiovascular disease 1

Special Populations

Pregnancy and Lactation

• Acetaminophen 1000 mg is first-line treatment during pregnancy. 2, 4
• NSAIDs can be used prior to the third trimester. 2
• Sumatriptan may be an option during pregnancy for selected patients and is compatible with breast-feeding. 4

Uncontrolled Hypertension

• Acetaminophen 1000 mg is the safest first-line analgesic when hypertension is uncontrolled, because it does not raise blood pressure or cardiovascular risk. 1
• NSAIDs are contraindicated in uncontrolled hypertension as they can further elevate blood pressure. 1

Essential Lifestyle Modifications

Counsel all patients on modifiable triggers and lifestyle factors that reduce migraine frequency: 1, 5, 2

• Maintain adequate hydration
• Ensure sufficient and consistent sleep (avoid sleep deprivation)
• Regular meals
• Regular aerobic exercise
• Stress management techniques
• Weight loss if overweight or obese
• Avoid excessive caffeine intake
• Address obstructive sleep apnea if present
• Manage psychiatric comorbidities (depression, anxiety)

Headache Diary

• Advise patients to keep a headache diary (paper or smartphone app) to track frequency, severity, triggers, and acute medication use—this improves accuracy of attack-frequency reporting and helps identify modifiable triggers. 1

Cost Considerations

• Prescribe less costly recommended medications when equally effective options exist—generic NSAIDs and older triptans are significantly less expensive than newer agents. 2