What is the optimal diagnostic and therapeutic approach for migraine, including acute abortive therapy, preventive medications, and lifestyle modifications?

Migraine: Diagnostic and Therapeutic Approach

When to Suspect Migraine

Suspect migraine in patients presenting with recurrent moderate-to-severe headaches, especially when accompanied by visual aura, family history of migraine, or symptom onset around puberty. 1

Key clinical features to identify:

• Recurrent attacks of headache lasting 4-72 hours when untreated 1
• Moderate to severe intensity that interferes with daily activities 1
• Unilateral location and pulsating quality in most cases 1
• Accompanying symptoms: nausea, vomiting, photophobia, or phonophobia 1
• Visual aura (fortification spectra) occurs in approximately one-third of patients, typically spreading gradually over ≥5 minutes 1

Critical distinction: Aura symptoms spread gradually over ≥5 minutes and occur in succession, whereas transient ischemic attack symptoms have sudden, simultaneous onset. 1

Diagnostic Approach

Apply International Classification of Headache Disorders (ICHD) diagnostic criteria after recording a thorough medical history, and perform physical examination only to exclude secondary causes—neuroimaging is indicated only when secondary headache disorder is suspected. 1

Essential diagnostic steps:

• Record detailed headache characteristics: frequency, duration, intensity, location, quality 1
• Identify trigger factors: stress, sleep changes, hormonal fluctuations, dietary factors 1
• Screen for red flags requiring urgent evaluation: abrupt onset ("thunderclap"), age ≥50 years at onset, presence of cancer or immunosuppression, neurologic signs, provocation by physical activity or postural changes 2
• Physical and neurological examination to exclude secondary causes 1
• Neuroimaging only when indicated: presence of red flags, atypical features, or progressive symptoms 1

Acute Abortive Therapy

First-Line Treatment for Mild-to-Moderate Attacks

NSAIDs are first-line treatment for mild-to-moderate migraine attacks, with ibuprofen 400-800 mg every 6 hours, diclofenac potassium, or acetylsalicylic acid (aspirin) 800-1000 mg as preferred options. 1, 3

• Administer medication early in the headache phase for maximum effectiveness 3
• Acetaminophen alone has limited efficacy and should only be used in patients intolerant to NSAIDs 3
• Combine with metoclopramide 10-20 mg for nausea and to enhance absorption 1

Second-Line Treatment for Moderate-to-Severe Attacks

Triptans (5-HT1B/D agonists) are recommended for moderate-to-severe attacks or when NSAIDs fail, with sumatriptan as the most studied option at a maximum dose of 200 mg in 24 hours. 1, 3, 2

• Triptans eliminate pain in 20-30% of patients by 2 hours 2
• Combining triptans with fast-acting NSAIDs prevents relapse and improves outcomes 1, 3
• Contraindications: cardiovascular disease, uncontrolled hypertension, hemiplegic migraine, basilar migraine 2
• Common adverse effects: transient flushing, tightness, or tingling in upper body (25% of patients) 2

Third-Line Treatment Options

CGRP receptor antagonists (gepants) such as rimegepant or ubrogepant eliminate headache in 20% of patients at 2 hours and are safe in patients with cardiovascular risk factors. 4, 2

• Rimegepant 75 mg orally achieves pain freedom in 21.2% vs 10.9% with placebo at 2 hours 4
• Adverse effects: nausea and dry mouth in 1-4% of patients 2
• Lasmiditan (5-HT1F agonist) is another alternative safe in cardiovascular disease 2

Critical Medication Overuse Warning

Limit triptans to <10 days/month and NSAIDs to <15 days/month to prevent medication-overuse headache. 3, 5

Preventive Medications

Indications for Preventive Therapy

Initiate preventive therapy for patients experiencing ≥2 migraine days per month with significant disability, or when acute treatments are contraindicated or ineffective. 3

First-Line Preventive Options

Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (50-100 mg daily), or amitriptyline are first-line preventive medications with consistent evidence of efficacy. 1, 3

Propranolol 80-240 mg/day is preferred for patients with comorbid hypertension 3, 5

Topiramate 50-100 mg daily is particularly beneficial in patients with comorbid obesity due to associated weight loss 3, 5

Amitriptyline is optimal for patients with comorbid depression or sleep disturbances 3

Second-Line Preventive Options

Flunarizine 5-10 mg daily, candesartan (angiotensin receptor blocker), or valproic acid (in men only) are second-line options when first-line agents fail. 5

• Flunarizine: avoid in patients with Parkinsonism or depression 5
• Valproic acid: absolutely contraindicated in women of childbearing potential due to teratogenicity 1, 5

Third-Line Preventive Options

CGRP monoclonal antibodies (erenumab 70-140 mg subcutaneous monthly, fremanezumab 225 mg monthly or 675 mg quarterly, galcanezumab, or eptinezumab 100-300 mg intravenous quarterly) are third-line medications for refractory cases. 5, 6

• Fremanezumab reduces migraine by 3.4-3.7 days per month vs 2.2 days with placebo 6
• 47.7% of patients achieve ≥50% reduction in monthly migraine days 6
• OnabotulinumtoxinA 155-195 units to 31-39 sites every 12 weeks is FDA-approved for chronic migraine (≥15 headache days/month) 5, 2

Treatment Assessment and Duration

Evaluate treatment response after 2-3 months at therapeutic dose using headache calendars to track attack frequency, severity, and medication use. 1, 3

• Consider pausing preventive treatment after 6-12 months of successful control to determine if therapy can be stopped 5
• For CGRP monoclonal antibodies, assess efficacy after 3-6 months 5
• For onabotulinumtoxinA, assess efficacy after 6-9 months 5

Lifestyle Modifications

Implement lifestyle modifications as foundational therapy: maintain regular sleep schedule (7-8 hours), eat well-balanced meals at consistent times, ensure adequate hydration, engage in regular aerobic exercise, manage stress through relaxation techniques, and identify/avoid individual trigger factors. 5

Specific recommendations:

• Dietary modifications: limit excessive caffeine, alcohol, and nicotine; avoid skipping meals 5
• Sleep hygiene: establish consistent sleep-wake times 5
• Stress management: biobehavioral therapy, relaxation techniques, biofeedback 5
• Regular aerobic exercise is as effective as pharmacological approaches when combined with other interventions 5

Special Populations

Pregnant Women

Paracetamol (acetaminophen) 1000 mg is first-line acute treatment during pregnancy; avoid preventive medications unless absolutely necessary, and if required, use propranolol 80-160 mg daily as the safest option. 7

Acute treatment hierarchy:

• First-line: Paracetamol 1000 mg 7
• Second-line: Ibuprofen (second trimester only) 7
• Third-line: Sumatriptan sporadically under specialist supervision when other treatments fail 7

Absolutely contraindicated: Ergotamine derivatives, topiramate, valproate, candesartan 7

Non-pharmacological approaches should be tried first: hydration, regular meals, sufficient sleep, physical activity, trigger avoidance 7

Breastfeeding Women

Paracetamol remains preferred for acute treatment; ibuprofen and sumatriptan are safe during breastfeeding. For prevention, propranolol 80-160 mg daily has the best safety profile. 7

Children and Adolescents

Ibuprofen is first-line for acute treatment; bed rest alone can be sufficient. For prevention, use propranolol, amitriptyline, or topiramate when indicated. 1

• Presentation may differ from adults: shorter attack duration, bilateral location more common 1
• Parents and schools have important roles in management 1

Older Adults

Secondary headache, comorbidities, and adverse events are more likely in older patients; poor evidence base exists for all drugs in this age group, requiring cautious medication selection and lower starting doses. 1

Managing Treatment Failure

When outcomes are suboptimal, systematically review diagnosis accuracy, treatment strategy appropriateness, medication dosing, and patient adherence before changing therapy. 1

Algorithm for treatment failure:

1. Confirm diagnosis: ensure migraine criteria are met, not secondary headache 1
2. Assess medication timing: verify early administration during attacks 1
3. Evaluate dosing: ensure therapeutic doses are used 1
4. Check adherence: use headache calendars to document compliance 1
5. Screen for medication overuse: limit acute medication frequency 1
6. Consider comorbidities: anxiety, depression, sleep disorders, obesity 3
7. Switch drug classes: failure of one preventive does not predict failure of others 5

Managing Complications

Medication-Overuse Headache

Discourage medication overuse and recognize established overuse early; withdraw overused medication, preferably abruptly, to prevent medication-overuse headache. 1

• Definition: ≥15 days/month with simple analgesics or ≥10 days/month with triptans 3, 5
• Management: abrupt withdrawal is preferred over gradual tapering 1

Chronic Migraine

Specialist referral is indicated for patients with chronic migraine (≥15 headache days per month). 1

Comorbidity Management

Identify and manage comorbid conditions—anxiety, depression, sleep disorders, obesity—to optimize migraine treatment outcomes. 3, 5

• Topiramate preferred in obesity due to weight loss effect 3
• Amitriptyline preferred with depression or sleep disturbances 3
• Beta-blockers preferred with hypertension 3, 5

Long-Term Follow-Up

Manage migraine long-term in primary care with regular follow-up every 2-3 months for stable patients; repatriate from specialist care with comprehensive treatment plan; maintain stability of effective treatment and react promptly to changes. 1, 5