What medications are used to treat migraines?

Medications for Migraine Treatment

For acute migraine treatment, NSAIDs (aspirin, ibuprofen, naproxen sodium) are first-line therapy for mild-to-moderate attacks, while triptans are first-line for moderate-to-severe attacks or when NSAIDs fail. 1, 2

Acute Treatment Medications

First-Line: NSAIDs (Mild-to-Moderate Migraine)

• Aspirin, ibuprofen, naproxen sodium, and the acetaminophen-aspirin-caffeine combination have the most consistent evidence for efficacy. 1, 2
• Acetaminophen alone is ineffective and should not be used as monotherapy. 1, 2
• Naproxen sodium dosing: 500-825 mg at onset, can repeat every 2-6 hours (maximum 1.5 g/day). 2
• Critical limitation: Use no more than twice weekly to prevent medication-overuse headache. 1, 2

First-Line: Triptans (Moderate-to-Severe Migraine)

• Oral triptans with good evidence: naratriptan, rizatriptan, sumatriptan, and zolmitriptan. 1, 2
• Sumatriptan 50-100 mg orally provides headache relief in approximately 60% of patients at 2 hours (NNT 3.4 for 100 mg dose). 3, 4
• Subcutaneous sumatriptan 6 mg is the most effective and rapidly acting option (70-82% response rate, peak concentration in 15 minutes, 59% pain-free at 2 hours). 1, 2, 5
• Intranasal formulations (sumatriptan, zolmitriptan) are useful when nausea/vomiting precludes oral administration. 1, 2, 6
• Absolute contraindications: uncontrolled hypertension, basilar or hemiplegic migraine, ischemic heart disease, or significant cardiovascular disease. 1, 2

Second-Line: Dihydroergotamine (DHE)

• Intranasal DHE has good evidence for efficacy and safety as monotherapy. 1, 2
• Intravenous DHE 0.5-1.0 mg is effective for refractory migraine or status migrainosus. 5, 7
• Contraindicated with concurrent triptan use, in pregnancy (oxytocic properties), and with peripheral vascular disease. 1, 8

Adjunctive: Antiemetics

• Metoclopramide 10 mg IV or oral provides direct analgesic effects beyond treating nausea through central dopamine receptor antagonism. 1, 2
• Prochlorperazine 10 mg IV or 25 mg suppository effectively relieves both headache pain and nausea. 1, 2, 5
• Administer 20-30 minutes before NSAIDs or triptans to enhance absorption and provide synergistic analgesia. 1, 2

Rescue Medications (Last Resort)

• Opioids (butorphanol nasal spray) should only be used when other medications cannot be used, sedation is not a concern, and abuse risk has been addressed. 1, 2
• Avoid establishing patterns of frequent opioid use due to risk of dependency, rebound headaches, and loss of efficacy. 1, 2, 7

Emergency Department/Severe Migraine Protocol

IV Combination Therapy

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV is first-line combination therapy for severe attacks requiring IV treatment. 2, 5, 7
• Ketorolac has rapid onset (approximately 6 hours duration) with minimal rebound headache risk. 2
• Add IV fluids for hydration, as dehydration worsens migraine symptoms. 7

Status Migrainosus

• Use the IV combination above (metoclopramide + ketorolac) immediately. 7
• Consider subcutaneous sumatriptan 6 mg if no serotonergic agents used during this attack. 7
• Status migrainosus is an absolute indication to initiate preventive therapy. 7

Preventive Medications

Indications for Preventive Therapy

• ≥2 migraine attacks per month producing ≥3 days of disability 1, 7
• Use of acute medications more than twice weekly 1, 7
• Failure of or contraindications to acute treatments 1
• Uncommon migraine conditions (prolonged aura, migrainous infarction, hemiplegic migraine) 1

First-Line Preventive Agents

• Propranolol 80-240 mg/day or timolol 20-30 mg/day (beta blockers with strongest evidence). 1, 7
• Amitriptyline 30-150 mg/day (particularly useful for mixed migraine and tension-type headache). 1, 7
• Divalproex sodium 500-1,500 mg/day or sodium valproate 800-1,500 mg/day (caution: teratogenic potential, weight gain, tremor). 1, 7
• Topiramate is also first-line but has similar adverse effect profile to valproate. 7

Critical Pitfalls to Avoid

• Never allow acute medication use more than 2 days per week—this creates medication-overuse headache and paradoxically increases attack frequency. 1, 2, 7
• Rebound headache occurs with withdrawal of opiates, triptans, ergotamine, and analgesics containing caffeine, isometheptene, or butalbital. 1
• Do not use triptans and ergot derivatives within 24 hours of each other due to additive vasoconstrictive effects. 1, 5
• When a triptan fails, try a different triptan before abandoning the class—failure of one does not predict failure of others. 2
• Transition to preventive therapy when patients require acute treatment more than twice weekly rather than increasing frequency of acute medications. 2, 7