What is the recommended treatment algorithm for migraines?

Migraine Treatment Algorithm

Use a stepped care approach starting with NSAIDs for mild-to-moderate attacks, escalating to triptans for moderate-to-severe attacks or NSAID failures, and implementing preventive therapy for patients with ≥2 disabling migraine days per month despite optimized acute treatment. 1

Acute Treatment Strategy

First-Line: NSAIDs for Mild-to-Moderate Attacks

• Start with acetylsalicylic acid (aspirin), ibuprofen, or diclofenac potassium as these have the strongest evidence for efficacy 2, 1
• Aspirin-acetaminophen-caffeine combination is highly effective (number needed to treat = 4 for pain relief at 2 hours) 3
• Paracetamol alone has inferior efficacy and should only be used if NSAIDs are contraindicated 2
• Administer medication early in the attack while headache is still mild for maximum effectiveness 2, 1

Second-Line: Triptans for Moderate-to-Severe Attacks

• Offer triptans when NSAIDs provide inadequate relief 2, 1
• All triptans have well-documented effectiveness; if one fails, try another as individual response varies 2
• Take triptans early during the headache phase (not during aura) for optimal efficacy 2, 1
• Combine triptans with NSAIDs (particularly naproxen) to reduce relapse rates 2, 3
• Subcutaneous sumatriptan is reserved for patients with rapid peak intensity or severe vomiting preventing oral intake 2, 3

Third-Line: CGRP Antagonists and Other Options

• For triptan failures or contraindications, use gepants (rimegepant, ubrogepant, zavegepant), lasmiditan, or dihydroergotamine 3
• Ubrogepant and rimegepant have a number needed to treat of 13 for pain freedom at 2 hours 3
• Lasmiditan shows robust benefit but causes significant adverse effects including driving restrictions (number needed to harm = 4) 3

Managing Associated Symptoms

• Use non-oral routes (nasal spray, subcutaneous injection, suppository) for patients with early-onset nausea or vomiting 2, 3
• Add antiemetics (metoclopramide or prochlorperazine) to treat nausea and improve gastric motility 2, 3
• Nausea itself is disabling and warrants treatment even without vomiting 2

Critical Pitfalls to Avoid

• Avoid opioids and butalbital-containing analgesics as these promote medication overuse headache and dependency 3
• Limit acute medication use to prevent medication overuse headache: ≤10 days/month for triptans, ≤15 days/month for NSAIDs 1, 3

Preventive Treatment Strategy

Indications for Preventive Therapy

Initiate preventive therapy when patients have: 2, 1, 3

• ≥2 attacks per month producing disability lasting ≥3 days per month
• Contraindication to or failure of acute treatments
• Use of acute medication more than twice per week
• Uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction)

First-Line Preventive Medications

Beta-blockers and topiramate are the primary first-line options: 1, 3

• Propranolol 80-240 mg/day 2
• Timolol 20-30 mg/day 2
• Metoprolol, atenolol, or bisoprolol 1
• Topiramate (requires discussion of teratogenic effects with patients of childbearing potential) 3
• Amitriptyline 30-150 mg/day 2
• Divalproex sodium 500-1500 mg/day or sodium valproate 800-1500 mg/day 2

Second-Line Options

• ACE inhibitors or ARBs if first-line agents are not tolerated 3
• SSRIs for patients with comorbid depression 3

Third-Line: CGRP Monoclonal Antibodies and OnabotulinumtoxinA

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) for patients failing oral preventives 1, 4
• Erenumab 70-140 mg subcutaneously once monthly reduces monthly migraine days by 2.5 days compared to placebo 4
• OnabotulinumtoxinA 155 units is specifically FDA-approved for chronic migraine (≥15 headache days/month) based on large-scale trials 3

Preventive Therapy Management

• Start at low doses and titrate slowly until clinical benefit or adverse effects limit further increase 2
• Allow 2-3 months for full therapeutic effect before declaring treatment failure 2, 1
• Monitor with headache diaries tracking attack frequency, severity, medication use, and disability 2, 3
• Evaluate treatment response at 2-3 months, then every 6-12 months 1
• Consider tapering or discontinuing after a period of stability 2

Non-Pharmacologic Interventions

Behavioral Therapies

• Offer cognitive-behavioral therapy, biofeedback, and relaxation training to all patients as these have good evidence for efficacy 3
• These should be part of comprehensive management, not alternatives to medication 3

Lifestyle Modifications

• Regular moderate-to-intense aerobic exercise (40 minutes three times weekly) is as effective as some preventive medications 3
• Maintain regular meals, adequate hydration, and sufficient sleep 3
• Manage stress with relaxation techniques or mindfulness practices 3
• Address poor sleep quality and physical fitness as predisposing factors 2, 3

Important caveat: While lifestyle modifications are recommended, avoid creating unnecessary avoidance behaviors that damage quality of life 2. True trigger factors are often self-evident and should not be overemphasized 2.

Special Populations

Chronic Migraine (≥15 Headache Days/Month)

• Rule out secondary causes before establishing chronic migraine diagnosis 3
• OnabotulinumtoxinA 155 units is the specific FDA-approved treatment 3, 4
• Monitor closely for medication overuse headache and limit acute medication use 3

Children and Adolescents

• Ibuprofen at appropriate weight-based dosing is first-line acute treatment 3
• For prevention, consider propranolol, amitriptyline, or topiramate 3
• Approximately two-thirds of pediatric patients improve with standard therapy 2

Women with Menstrual Migraine

• Short-term prevention with NSAIDs or triptans around menstruation 1
• Combined hormonal contraceptives may benefit women with pure menstrual migraine without aura 1

Older Adults

• Consider comorbidities and potential drug interactions when selecting treatments 1
• Be vigilant for late-onset migraine (after age 50) as this raises suspicion for underlying secondary causes 1

Monitoring and Follow-Up

Assess for Medication Overuse Headache

• Monitor patients using acute medications ≥10 days/month (triptans) or ≥15 days/month (NSAIDs) 1
• Educate all patients about this risk at treatment initiation 1, 3

Identify and Manage Comorbidities

• Screen for anxiety, depression, sleep disorders, and obesity 1
• Adjust treatments considering interactions between medication side effects and patient comorbidities 1

Track Treatment Outcomes

• Use headache calendars to document attack frequency, severity, and medication use 2, 1, 3
• Assess migraine-related disability using validated tools 1
• Switch preventive treatment if adequate response is not achieved during a reasonable trial period 3