What medications are used to treat migraines?

Medications for Migraine Treatment

First-Line Acute Treatment

For mild to moderate migraine attacks, NSAIDs are the primary treatment, while triptans should be used for moderate to severe attacks or when NSAIDs fail. 1

NSAIDs (Mild to Moderate Attacks)

• Aspirin, ibuprofen, naproxen sodium, and the acetaminophen-aspirin-caffeine combination have the strongest evidence for efficacy 2
• Naproxen sodium should be dosed at 500-825 mg at migraine onset, ideally when pain is still mild, and can be repeated every 2-6 hours as needed (maximum 1.5 g per day) 1
• Acetaminophen alone is ineffective and should not be used as monotherapy 2
• Ketorolac 30-60 mg IV/IM provides rapid onset (approximately 6 hours duration) with minimal rebound headache risk 1

Triptans (Moderate to Severe Attacks)

• Oral triptans with good evidence include naratriptan, rizatriptan, sumatriptan, and zolmitriptan 2, 1
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) and fastest onset (15 minutes to peak concentration), making it the most effective route for severe attacks 1, 3
• Intranasal sumatriptan (5-20 mg) is particularly useful when significant nausea or vomiting is present 1
• Triptans are contraindicated in patients with uncontrolled hypertension, coronary artery disease, basilar or hemiplegic migraine, or cardiovascular risk factors 2, 3
• Oral sumatriptan dosing: 25-100 mg at onset, with a second dose only if some response occurred to the first dose, separated by at least 2 hours (maximum 200 mg per 24 hours) 3

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg IV provides both direct analgesic effects through dopamine receptor antagonism and synergistic pain relief when combined with other medications 1
• Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide in efficacy, with a more favorable side effect profile (21% adverse events vs 50% with chlorpromazine) 1
• Antiemetics should be administered 20-30 minutes before NSAIDs to enhance absorption and provide synergistic analgesia 1
• Nausea itself warrants treatment even without vomiting, as it is one of the most disabling migraine symptoms 1

Combination Therapy

• Adding metoclopramide or prochlorperazine to naproxen provides synergistic analgesia and improves outcomes compared to naproxen alone 1
• The acetaminophen-aspirin-caffeine combination is effective for moderate attacks, as caffeine enhances absorption and efficacy of analgesics 2, 1
• For severe attacks requiring IV treatment, metoclopramide 10 mg IV plus ketorolac 30 mg IV is recommended as first-line combination therapy 1

Second-Line and Rescue Treatments

• Dihydroergotamine (DHE) intranasal has good evidence for efficacy and safety as monotherapy for acute migraine attacks 2, 1
• Butorphanol nasal spray has good evidence for efficacy but should be reserved for refractory cases 2
• Opioids should only be considered when other evidence-based treatments have failed or are contraindicated, sedation is not a concern, and abuse risk has been addressed 2, 1
• Opioids lead to dependency, rebound headaches, and eventual loss of efficacy, particularly problematic in chronic daily headaches 1

Critical Medication Overuse Prevention

Acute treatment must be limited to no more than twice weekly to prevent medication-overuse headache (MOH). 2, 1

• Rebound headaches are associated with withdrawal of analgesics, triptans, ergotamine, and medications containing caffeine, isometheptene, or butalbital 2
• If patients require acute treatment more than 2 days per week, preventive therapy is indicated 1
• MOH can result from frequent use of any acute medication (≥15 days/month with NSAIDs or ≥10 days/month with triptans) 4

Preventive Therapy Indications

Preventive therapy should be considered when: 2

• Two or more migraine attacks per month producing disability for 3+ days
• Use of rescue medication more than twice weekly
• Failure of acute treatments or contraindications to acute medications
• Presence of uncommon migraine conditions (prolonged aura, migrainous infarction, hemiplegic migraine)

First-Line Preventive Agents

• Propranolol 80-240 mg/day 2
• Timolol 20-30 mg/day 2
• Amitriptyline 30-150 mg/day 2
• Divalproex sodium 500-1,500 mg/day 2
• Sodium valproate 800-1,500 mg/day 2

Treatment Algorithm for Failed Response

When current medication stops working: 1

1. First, rule out medication-overuse headache if using acute medications more than twice weekly
2. Try a different triptan, as failure of one does not predict failure of others
3. Ensure early administration during attacks while pain is still mild
4. Consider route change (e.g., subcutaneous if oral fails), particularly for rapid-onset attacks or vomiting
5. Add combination therapy with fast-acting NSAIDs to prevent the 40% recurrence rate within 48 hours
6. If all triptans fail after adequate trials, escalate to third-line agents like ditans or gepants
7. Initiate preventive therapy if headaches continue despite optimized acute therapy

Status Migrainosus (Prolonged Attack >72 Hours)

• Administer IV metoclopramide 10 mg plus IV ketorolac 30 mg immediately for rapid pain relief 5
• Add IV fluids for hydration, as dehydration worsens migraine symptoms 5
• Consider subcutaneous sumatriptan 6 mg if no serotonergic agents used during this attack 5
• Status migrainosus is an absolute indication for preventive therapy to prevent recurrence 5
• Avoid opioids, as they lead to dependency and rebound headaches 5

Common Pitfalls to Avoid

• Never allow patients to increase frequency of acute medication use in response to treatment failure—this creates a vicious cycle of MOH; instead transition to preventive therapy 1
• Do not use acetaminophen alone, as it is ineffective for migraine 2
• Avoid oral ergot alkaloids, opioids, and barbiturates due to questionable efficacy and high risk of adverse effects 4
• Do not restrict metoclopramide only to vomiting patients—nausea alone warrants treatment 1
• Begin treatment as early as possible during attacks to improve efficacy 2, 1