What are the steps for treating a patient with migraines, including lifestyle modifications and medication options?

Migraine Treatment: Stepwise Guideline-Based Approach

Initial Assessment and Red Flags

Before initiating migraine treatment, rule out secondary headaches by checking for thunderclap onset, atypical aura, recent head trauma, progressive worsening, or new headache after age 50. 1

Step 1: Patient Education and Realistic Expectations

• Explain that migraine is a chronic neurological disorder that cannot be cured, but can be controlled to reduce attack frequency, duration, and intensity 2
• Set the realistic goal of returning control from the disease to the patient, allowing continuation of life with minimal hindrance 2
• Educate on proper medication use, potential adverse effects, and the critical importance of avoiding medication overuse (≥15 days/month for NSAIDs or ≥10 days/month for triptans) 1
• Emphasize that adherence is crucial because improvement occurs gradually, with effects becoming apparent after the first few weeks of treatment 2

Step 2: Lifestyle Modifications and Trigger Management

• Counsel on maintaining regular sleep schedules, adequate hydration, regular physical activity, and avoiding starvation 2
• Address modifiable risk factors including obesity, caffeine overuse, obstructive sleep apnea, and psychiatric comorbidities (anxiety, depression) 3
• Keep in mind that true trigger factors are often self-evident and their role is frequently overemphasized 2
• Avoid unnecessary avoidance behaviors that can damage quality of life 2

Step 3: Acute Treatment - Stratified Approach

First-Line: NSAIDs (for mild to moderate migraine)

Start with NSAIDs as first-line treatment: ibuprofen 400-800 mg, diclofenac potassium, or acetylsalicylic acid (aspirin). 2, 1

• Ibuprofen 400 mg is preferred over 200 mg for superior efficacy 1
• Naproxen sodium 500-825 mg is also effective 1
• Acetaminophen should only be used in patients intolerant to NSAIDs due to inferior efficacy 2, 1
• Take medication early in the attack when headache is still mild for maximum effectiveness 2, 1
• Limit use to fewer than 15 days per month to prevent medication overuse headache 1

Second-Line: Triptans (for moderate to severe migraine or NSAID failure)

Escalate to triptans when NSAIDs provide inadequate relief after 2-3 attempts. 2, 1

• All triptans have well-documented effectiveness: sumatriptan 50-100 mg, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan, or naratriptan 1, 4
• Sumatriptan tablets achieve headache response (reduction to mild or no pain) in 52-62% of patients at 2 hours and 65-79% at 4 hours, compared to 17-27% and 19-38% with placebo 4
• Triptans are most effective when taken early in the attack while pain is still mild 2, 1
• A second dose may be considered if some response to the first dose was observed, separated by at least 2 hours 4
• Maximum dose in 24 hours: 200 mg for sumatriptan 4
• Limit triptan use to ≤10 days per month to avoid medication overuse headache 1, 5
• Consider non-oral routes (subcutaneous, intranasal) for patients with severe nausea/vomiting 1

Third-Line: CGRP Antagonists (Gepants) (for triptan failure or contraindication)

Use CGRP antagonists—rimegepant, ubrogepant, or zavegepant—when triptans fail or are contraindicated. 1

• Unlike triptans and ergot alkaloids, gepants do not have vascular contraindications 6
• Cost is a significant limiting factor for these newer agents 2, 6

Adjunct Therapy: Antiemetics

• Add prokinetic antiemetics (metoclopramide or domperidone) for nausea/vomiting 1
• Antiemetics can be used in combination with analgesics or triptans 2

Medications to Avoid

Never use opioids or butalbital-containing compounds due to risk of dependency, medication overuse headache, and eventual loss of efficacy. 2, 1, 5, 6

• Oral ergot alkaloids should also be avoided due to questionable efficacy with considerable adverse effects 3

Step 4: When to Consider Preventive Therapy

Initiate preventive therapy if migraines significantly impact quality of life despite optimized acute treatment, or if the patient experiences ≥2 migraine days per month with significant disability. 2, 1

Additional indications include:

• Severe debilitating headaches despite adequate acute treatment 2
• Inability to tolerate or contraindications to acute treatment 2
• Using acute treatment more often than recommended (approaching medication overuse thresholds) 2

Step 5: Preventive Treatment - Prioritized Approach

First-Line Preventive Medications (choose based on comorbidities and cost)

The American College of Physicians recommends using β-blockers (metoprolol or propranolol), valproate, venlafaxine (SNRI), or amitriptyline (TCA) as first-line preventive therapy before considering more expensive CGRP-based treatments. 2

• β-blockers (propranolol 80-240 mg/day, metoprolol, atenolol, or timolol): Particularly useful in patients with comorbid hypertension 2, 1, 3, 5
• Amitriptyline (10-100 mg at night): Especially beneficial for patients with coexisting anxiety or depression 2, 1, 3
• Valproate (600-1,500 mg daily): Effective but absolutely contraindicated in women of childbearing potential due to teratogenicity 2, 3
• Venlafaxine (SNRI): Alternative first-line option 2

Second-Line Options (if first-line agents fail or are not tolerated)

• Topiramate (50-100 mg daily): Especially beneficial in obese patients, but common adverse effects include cognitive inefficiency, paresthesia, and fatigue 2, 3
• Candesartan (ARB): Particularly useful in hypertensive patients 2, 3
• Fluoxetine (SSRI): Consider if other options fail 2
• Lisinopril (ACE inhibitor): Alternative option 2

Third-Line: CGRP-Based Therapies (for refractory cases)

Use CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, or galcanezumab) or CGRP antagonist-gepants (atogepant or rimegepant) only after trials of first-line agents have failed. 2

• CGRP-mAbs and gepants are substantially more costly than traditional preventive medications 2
• Assess efficacy after 3-6 months for CGRP-mAbs 3
• These agents do not have vascular contraindications, making them suitable for patients with cardiovascular risk factors 6

Special Consideration: Chronic Migraine

• OnabotulinumtoxinA (155-195 units to 31-39 sites every 12 weeks): Only FDA-approved therapy for prophylaxis of chronic migraine (≥15 headache days per month) 3
• Assess efficacy after 6-9 months 3

Step 6: Treatment Initiation and Monitoring

• Initiate preventive medications at low doses and gradually titrate upward until desired outcomes are achieved 2
• Assess efficacy of oral preventive medications after 2-3 months at therapeutic dose 2, 3
• Switch medications if adequate response is not achieved during this trial period, or earlier if adverse effects occur 2
• Consider pausing preventive treatment after 6-12 months of successful control to determine if therapy can be stopped 3
• Encourage patients to maintain a headache diary to facilitate monitoring of attack frequency and treatment response 3

Step 7: Nutraceuticals and Supplements (adjunctive therapy)

• Magnesium citrate, riboflavin (vitamin B2), and coenzyme Q10 have favorable evidence for migraine prevention 7, 8
• These can be used alongside prescription medications or as initial therapy in patients preferring natural treatments 7, 8

Critical Pitfalls to Avoid

• Never allow patients to increase acute medication frequency in response to frequent attacks; instead, transition to prophylactic therapy 5
• Do not abandon preventive treatment prematurely—efficacy takes weeks to months to establish 3
• Avoid conflating aggravating factors (which worsen headache during attacks, like physical activity) with predisposing factors (which increase susceptibility, like poor sleep) 2
• Do not prescribe triptans without screening for cardiovascular contraindications: history of coronary artery disease, stroke, uncontrolled hypertension, or peripheral vascular disease 4
• Failure of one preventive treatment does not predict failure of other drug classes—try different medication classes sequentially 3