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Evidence-Based Guidelines for the Pharmacological Treatment of Migraine (Updated April 2025)

Posted on April 25 2025, By: Cerebral Torque

Evidence-Based Guidelines for the Pharmacological Treatment of Migraine

A comprehensive summary of treatment recommendations from the Italian Society for the Study of Headache and International Headache Society
Cephalalgia | April 2025

About These Guidelines

These evidence-based guidelines provide clear, actionable recommendations to healthcare professionals for the pharmacological treatment of migraine. The guidelines follow the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation) for assessing the quality of evidence and strength of recommendations.

Understanding Recommendation Strength and Evidence Quality

  • Strong recommendations ("we recommend") indicate high confidence that benefits outweigh risks
  • Weak recommendations ("we suggest") indicate benefits likely outweigh risks, but there is less certainty
  • High quality evidence means we have high certainty the true effect is close to the estimated effect
  • Moderate quality evidence means we have moderate certainty in the estimate of effect
  • Low quality evidence means our confidence is limited in the estimate of effect
  • Very low quality evidence means we have very little confidence in the estimate of effect

Acute Treatment of Migraine

These medications are used to treat migraine attacks once they have started. The primary outcomes considered were pain freedom and pain relief at 2 hours after medication intake.

Medication Dose Evidence Quality Recommendation
Acetaminophen (Paracetamol) 1000 mg oral High Strong
Acetylsalicylic acid (Aspirin) 1000 mg oral Moderate Strong
Diclofenac 50 mg oral Moderate Strong
Ibuprofen 200, 400, 600 mg oral Low Strong
Naproxen 500 and 825 mg oral Very Low Strong
Celecoxib 120 mg oral Moderate Weak
Triptan Dose Evidence Quality Recommendation
Almotriptan 12.5 mg oral High Strong
Eletriptan 20 and 40 mg oral High Strong
Frovatriptan 2.5 mg oral High Strong
Naratriptan 1 and 2.5 mg oral High Strong
Rizatriptan 5 and 10 mg oral High Strong
Sumatriptan 50 and 100 mg oral High Strong
Sumatriptan 6 mg/mL subcutaneous High Strong
Sumatriptan 10 and 20 mg intranasal High Strong
Zolmitriptan 2.5 mg oral High Strong
Newer Treatments Dose Evidence Quality Recommendation
Lasmiditan (Reyvow) 50, 100 and 200 mg oral High Strong
Rimegepant (Nurtec ODT) 75 mg oral High Strong
Ubrogepant (Ubrelvy) 50 and 100 mg oral High Strong
Zavegepant (Zavzpret) 10 mg intranasal High Strong
Zavegepant (Zavzpret) 20 mg intranasal Moderate Weak
Combination Therapies Dose Evidence Quality Recommendation
Acetylsalicylic acid (Aspirin) + Acetaminophen (Paracetamol) + Caffeine 500 mg + 500 mg + 130 mg oral High Strong
Acetylsalicylic acid (Aspirin) + Metoclopramide 900 mg + 10 mg oral Moderate Strong
Sumatriptan + Naproxen (Treximet) 85 mg + 500 mg oral Low Strong
Rizatriptan + Acetaminophen (Paracetamol) 10 mg + 1000 mg oral Low Strong
Acetaminophen (Paracetamol) + Tramadol 650 mg + 75 mg oral Moderate Weak

Preventive Treatment for Episodic Migraine

Preventive treatments are used to reduce the frequency and severity of migraine attacks. The primary outcomes considered include reduction in monthly migraine days and ≥50% responder rate.

Medication Dose Evidence Quality Recommendation
Atogepant (Qulipta) 60 mg oral High Strong
Erenumab (Aimovig) 70 and 140 mg every four weeks, subcutaneous High Strong
Fremanezumab (Ajovy) 225 mg monthly or 675 mg quarterly, subcutaneous High Strong
Galcanezumab (Emgality) 120 mg monthly, subcutaneous High Strong
Eptinezumab (Vyepti) 100 and 300 mg quarterly, intravenous Moderate Strong
Topiramate 100 and 200 mg oral Moderate Strong
Topiramate 50 mg oral Low Weak
Amitriptyline 25 mg oral Moderate Weak
Candesartan 16 mg oral Moderate Weak
Lisinopril 20 mg oral Low Weak
Propranolol 160 mg oral Low Weak
Valproate 750 mg and 1500 mg oral Very Low Weak

Preventive Treatment for Chronic Migraine

Chronic migraine is defined as headache occurring on 15 or more days per month for more than 3 months, with features of migraine on at least 8 days per month.

Medication Dose Evidence Quality Recommendation
OnabotulinumtoxinA (Botox) 155–195 IU intramuscular High Strong
Atogepant (Qulipta) 60 mg oral High Strong
Eptinezumab (Vyepti) 100 and 300 mg quarterly, intravenous High Strong
Fremanezumab (Ajovy) 675 mg quarterly, subcutaneous High Strong
Galcanezumab (Emgality) 120 mg monthly, subcutaneous High Strong
Erenumab (Aimovig) 70 and 140 mg every four weeks, subcutaneous Moderate Strong
Fremanezumab (Ajovy) 225 mg monthly, subcutaneous Moderate Strong
Topiramate 200 mg oral Low Weak
Topiramate 50 and 100 mg oral Very Low Weak

Head-to-Head Comparisons

These recommendations are based on direct comparison trials between different treatments.

Acute Treatment Comparisons
  • Eletriptan 40 mg is superior to Sumatriptan 100 mg (High quality, Strong recommendation)
  • Triptans are superior to Ergotamine + Caffeine (Moderate to Very low quality, Strong recommendation)
  • Rizatriptan 10 mg is superior to Ibuprofen 400 mg (Low quality, Weak recommendation)
  • Eletriptan 40 mg is superior to Naratriptan 2.5 mg (Moderate quality, Weak recommendation)
  • Combination therapies are generally superior to monotherapies (Low to Very low quality, Weak recommendation)
Preventive Treatment Comparisons
  • Erenumab 70 or 140 mg is superior to Topiramate up to 100 mg (Low quality, Strong recommendation)
  • Topiramate 50 mg is superior to Propranolol 80 mg (Very low quality, Weak recommendation)
  • Flunarizine 10 mg is superior to Metoprolol 200 mg (Low quality, Weak recommendation)
  • Metoprolol 200 mg is superior to Acetylsalicilic acid 300 mg (Very low quality, Weak recommendation)

Clinical Implications

Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies.

Key Considerations for Patients

  • Newer treatments (CGRP monoclonal antibodies, gepants, ditans) generally have higher quality evidence than older treatments
  • For acute treatment, triptans and NSAIDs remain cornerstone therapies with strong recommendations
  • For prevention, CGRP pathway-targeted treatments have transformed the treatment landscape
  • Some patients may be "late responders" to preventive treatments, showing benefits only after 3-4 months
  • Even a 30-49% reduction in monthly migraine days may represent a meaningful improvement for patients with treatment-resistant migraine
  • Combination approaches may be beneficial for patients with difficult-to-treat migraine

Special Populations

  • Older patients may respond better to certain treatments (e.g., increased age was associated with better response to erenumab)
  • Patients with chronic migraine and medication overuse may require different treatment approaches
  • Patients with unilateral headache may respond better to certain treatments
  • Women of childbearing potential should avoid valproate due to teratogenic risk
  • These guidelines do not address treatment for pediatric populations (under 18 years)

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