What is the best treatment for an adult patient with no significant medical history experiencing migraines?

Migraine Treatment: Evidence-Based Approach

Acute Treatment for Moderate to Severe Migraine

For adults with moderate to severe migraine, start with combination therapy of a triptan plus an NSAID—this is the most effective initial treatment, with 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to triptan alone. 1

First-Line Acute Treatment Algorithm

Mild to Moderate Attacks:

• Start with NSAIDs (ibuprofen, naproxen, diclofenac) or aspirin-acetaminophen-caffeine combination 1, 2
• Acetaminophen 1000 mg is less effective and should only be used if NSAIDs are contraindicated 1

Moderate to Severe Attacks or NSAID Failure:

• Combination therapy: Triptan + NSAID 1, 2
  • Sumatriptan 50-100 mg + naproxen 500 mg is the best-studied combination 3
  • Alternative NSAIDs include aspirin, celecoxib, diclofenac, or ibuprofen 3
• Take medication early in the attack when headache is still mild for maximum effectiveness 1
• Do not take triptans during the aura phase—they are ineffective at this stage 1

For Patients Intolerant to NSAIDs:

• Triptan + acetaminophen 1000 mg (lower certainty evidence but directionally favorable) 1, 3

Second-Line Options for Refractory Cases

When triptan-NSAID combinations fail:

• CGRP antagonists (gepants): rimegepant, ubrogepant, or zavegepant 3
• Dihydroergotamine, particularly intranasal formulation 3
• Sumatriptan subcutaneous injection for patients who rapidly reach peak intensity or cannot take oral medications due to vomiting 1

Critical Medications to AVOID

Never use opioids or butalbital-containing medications for acute migraine treatment—these carry risks of dependency, rebound headaches, and medication overuse headache. 1, 3

Preventing Medication Overuse Headache

• Limit triptan use to <10 days per month 3
• Limit NSAID/acetaminophen use to <15 days per month 3
• Overuse of acute medications leads to medication overuse headache, which presents as daily headaches or marked increase in migraine frequency 4

Preventive Treatment Strategy

Indications for Preventive Therapy

Consider preventive treatment when patients have: 2

• ≥2 attacks per month producing disability lasting ≥3 days per month
• Use of acute medications more than twice weekly
• Contraindications to acute treatments
• Uncommon migraine variants (hemiplegic, basilar)

First-Line Preventive Medications

Choose from these evidence-based options: 2

• Topiramate 50-100 mg daily (only oral medication proven effective for chronic migraine in randomized trials)
• Beta-blockers (propranolol, metoprolol)
• Amitriptyline 10-100 mg at night

Selection strategy: Match medication to comorbidities when possible 2

• Amitriptyline for patients with depression and migraine
• Beta-blockers for patients with hypertension and migraine
• Topiramate has the strongest evidence for chronic migraine specifically 2

Second-Line Preventive Options

• Venlafaxine (less supporting evidence, more adverse events) 1
• Flunarizine 5-10 mg daily (avoid in patients with Parkinsonism or depression) 1
• Sodium valproate 600-1,500 mg daily (absolutely contraindicated in women of childbearing potential) 1

Third-Line Preventive Options

• OnabotulinumtoxinA 155-195 units to 31-39 sites every 12 weeks (FDA-approved for chronic migraine) 1
• CGRP monoclonal antibodies: erenumab 70-140 mg subcutaneous monthly, fremanezumab 225 mg monthly or 675 mg quarterly, eptinezumab 100-300 mg IV quarterly 1

Non-Pharmacologic Interventions

These should be integrated into comprehensive management: 2

• Cognitive-behavioral therapy (good evidence for efficacy)
• Biofeedback and relaxation training (good evidence for efficacy)
• Regular aerobic exercise 40 minutes three times weekly (as effective as topiramate or relaxation therapy) 2

Lifestyle Modifications

Essential components of migraine management: 2

• Adequate hydration
• Regular meals (avoid hypoglycemia triggers)
• Consistent, sufficient sleep patterns
• Identification and avoidance of personal triggers (though true triggers are often self-evident) 1

Special Considerations

Menstrual Migraine

For women with menstruation-related attacks: 1

• Perimenstrual preventive treatment with long-acting NSAID (naproxen) or triptan (frovatriptan, naratriptan) for 5 days, beginning 2 days before expected menstruation
• Avoid combined hormonal contraceptives in migraine with aura (increased stroke risk) 1

Treatment Failure Management

Common pitfalls to address before concluding treatment failure: 1

• Poor adherence to medication regimen
• Suboptimal dosing (some patients need higher doses, others need lower doses to reduce adverse effects)
• Medication overuse interfering with preventive medication effectiveness
• Incorrect diagnosis

If one triptan fails, try others—individual response varies significantly between different triptans 1

Monitoring and Follow-Up

• Evaluate treatment response within 2-3 months after initiation or change 1
• Use headache diaries to track attack frequency, severity, and medication use 1
• Regular follow-up every 6-12 months thereafter 1
• Assess effectiveness using validated tools like mTOQ-4 for acute medications or HURT questionnaire for overall treatment response 1

Practical Implementation

Stepped care approach: 1

1. Start with first-line medications based on attack severity
2. Escalate to combination therapy if monotherapy inadequate
3. Move to second-line options for refractory cases
4. Consider preventive therapy if using acute medications >2 times weekly

Patient education is critical: 1

• Explain migraine as a neurological disease with biological basis
• Set realistic expectations—goal is control and reduced disability, not complete cure
• Teach correct medication use and importance of early treatment
• Warn about medication overuse headache risks