What are the treatment and prevention options for migraine headaches?

Migraine Headache Treatment and Prevention

Acute Treatment Strategy

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) taken at the first sign of headache; for moderate to severe attacks or when NSAIDs fail, use a triptan combined with an NSAID, as this combination is superior to either agent alone. 1, 2

First-Line Acute Treatment Options

Mild to Moderate Attacks:

• NSAIDs are the initial choice: naproxen sodium 500-825 mg, ibuprofen 400-800 mg, or aspirin 1000 mg 1, 2
• Combination therapy with acetaminophen 1000 mg + aspirin + caffeine is effective when NSAIDs alone are insufficient 1, 2
• Take medication early when pain is still mild to maximize efficacy 2

Moderate to Severe Attacks:

• Oral triptans (sumatriptan 50-100 mg, rizatriptan, naratriptan, or zolmitriptan) combined with naproxen 500 mg provides the strongest evidence for efficacy 1, 2
• This combination yields 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 2
• Subcutaneous sumatriptan 6 mg is the most rapidly effective option, providing relief in 70-82% of patients within 15 minutes, with 59% achieving complete pain relief by 2 hours 2, 3
• Intranasal sumatriptan 5-20 mg is preferred when significant nausea or vomiting is present 2

Intravenous Treatment for Severe Attacks

The optimal IV "migraine cocktail" consists of metoclopramide 10 mg IV plus ketorolac 30 mg IV, providing rapid pain relief through complementary mechanisms. 2

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic effects 2
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 2
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy and a more favorable side effect profile (21% vs 50% adverse events with chlorpromazine) 2
• Dihydroergotamine (DHE) IV or intranasal is an effective alternative when other treatments fail 1, 2

Critical Medication Overuse Prevention

Limit all acute migraine medications 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, 2

• Using acute medications more than twice weekly creates a vicious cycle requiring transition to preventive therapy 1, 2
• Opioids (including hydromorphone) should be reserved only when other evidence-based treatments have failed, contraindications exist, sedation is acceptable, and abuse risk has been addressed 2
• Butorphanol nasal spray has better evidence than other opioids if one must be used 2

Contraindications to Triptans

Triptans are contraindicated in patients with: 3

• Ischemic heart disease or coronary artery vasospasm
• Uncontrolled hypertension
• Significant cardiovascular disease
• Concurrent MAO-A inhibitor use (causes 7-fold increase in sumatriptan levels)
• History of cerebrovascular events

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Preventive Treatment Strategy

Initiate preventive therapy for patients with ≥2 migraine attacks per month causing disability lasting ≥3 days, or those using acute medications more than twice weekly. 1, 4

First-Line Preventive Medications

Start with one of these evidence-based first-line agents based on comorbidities: 1, 4

Beta-blockers (preferred initial choice):

• Propranolol 80-240 mg/day in long-acting formulations 1, 4
• Timolol 20-30 mg/day 1
• Particularly appropriate for patients with comorbid hypertension or anxiety 4
• Contraindicated in asthma, heart failure, or significant bradycardia 4

Anticonvulsants:

• Topiramate (dose titrated gradually) 1, 4
• Divalproex sodium 500-1,500 mg/day 1, 4
• Critical warning: Both topiramate and valproate are teratogenic; discuss contraception and folate supplementation with all women of childbearing potential before prescribing 1, 4

Tricyclic Antidepressants:

• Amitriptyline 30-150 mg/day, especially effective for patients with mixed migraine and tension-type headache 1, 4

ACE Inhibitors/ARBs (alternative first-line):

• Candesartan or telmisartan 1, 4
• Lisinopril 1

Second-Line Preventive Medications

If first-line treatments fail or are not tolerated after an adequate 2-3 month trial: 1, 4

• Flunarizine 5-10 mg once daily 4
• Absolutely contraindicated in patients with Parkinsonism or depression 4
• Can cause extrapyramidal symptoms, particularly in elderly patients 4
• Venlafaxine (SNRI) 4

OnabotulinumtoxinA for Chronic Migraine

OnabotulinumtoxinA (Botox) is approved specifically for chronic migraine (≥15 headache days per month) and is as effective as oral preventives with lower discontinuation rates. 5, 6

• Requires 6-9 months to assess full efficacy 2
• Well tolerated with fewer systemic side effects than oral medications 6
• Serious warning: Can cause spread of toxin effects leading to breathing and swallowing problems; patients must be counseled on symptoms of botulism 5

Treatment Titration and Monitoring

Start all preventive medications at low doses and titrate gradually to minimize side effects. 1

• Allow 2-3 months for oral agents to demonstrate efficacy before declaring treatment failure 1, 4
• Define success as ≥50% reduction in attack frequency 4
• Use headache calendars to objectively track frequency, severity, and disability 4
• Do not combine preventive medications without first trying adequate monotherapy trials 4

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Non-Pharmacologic Approaches

Before initiating pharmacologic treatment, identify and address modifiable triggers including irregular sleep, dehydration, stress, and dietary factors. 1, 7

Behavioral Interventions

• Cognitive behavioral therapy and relaxation training are effective for migraine prevention 1, 6
• Biofeedback has first-line evidence for preventive treatment 2, 6
• Regular physical activity and stress management 1, 7
• Maintain consistent sleep patterns and adequate hydration 1, 7

Dietary Supplements with Evidence

In decreasing order of preference: 8, 6

• Magnesium (strongest evidence)
• Riboflavin (vitamin B2) - has shown efficacy in multiple randomized trials 2, 8, 6
• Coenzyme Q10 8, 6
• Feverfew 8, 6
• Melatonin 6

Alternative Therapies

• Acupuncture has positive findings from randomized trials and can be considered first-line 2, 6
• Neuromodulation devices are supported by evidence 7, 6

Common Dietary Triggers to Identify

Certain patients may be sensitive to: 8

• Tyramine and phenylethylamine (aged cheeses, processed meats)
• Monosodium glutamate (MSG)
• Aspartame
• Nitrates and nitrites
• Alcohol
• Excessive caffeine (though caffeine can also be therapeutic in combination products)

Use food diaries to identify individual triggers 8

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Critical Pitfalls to Avoid

Common errors that undermine treatment success: 1, 4

• Failing to address medication overuse, which perpetuates rebound headaches 1
• Discontinuing preventive treatment before 2-3 months, before therapeutic effect is achieved 1, 4
• Starting preventive medications at full doses rather than titrating gradually, causing unnecessary side effects 1
• Not limiting acute medication use to ≤2 days per week 1, 2
• Combining preventive medications without adequate monotherapy trials 4
• Prescribing topiramate or valproate to women of childbearing potential without discussing teratogenicity and contraception 1, 4

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Special Populations

Pediatric patients: Propranolol is specifically recommended for pediatric migraine prevention 4

Women of childbearing potential: Avoid topiramate and valproate if possible; if used, ensure effective contraception and folate supplementation 1, 4

Pregnancy: All preventive medications require careful risk-benefit consideration; both propranolol and flunarizine need special consideration 4

Elderly patients: Use flunarizine with extreme caution due to increased risk of extrapyramidal symptoms 4