2025 AHS Acute Migraine in the Emergency Department Guideline Summary

This is a condensed summary of the 2025 American Headache Society Guideline Update on Parenteral Pharmacotherapies for Acute Migraine in Adults in the Emergency Department (Robblee et al.), updating the 2016 guideline. Recommendations follow the AAN grading system: Level A (must/must not offer), Level B (should/should not offer), Level C (may/may not offer), and Level U (no recommendation due to insufficient evidence).

1. Dopamine Receptor Antagonists

Prochlorperazine IV — Level A (Must Offer)

• Dose: 10–12.5 mg IV
• Highly likely to be effective — multiple class I studies
• Superior to hydromorphone IV and sumatriptan SC
• Comparable to metoclopramide and chlorpromazine
• Consider co-administration of diphenhydramine 25 mg IV to reduce akathisia risk
• Adverse effects: Akathisia, sedation

Metoclopramide IV — Level B (Should Offer)

• Dose: 10 mg IV
• Likely effective — comparable to GONB, dexketoprofen, sumatriptan, ketorolac
• Combination with dexketoprofen provides enhanced benefit
• Adverse effects: Akathisia (anticholinergic premedication may reduce extrapyramidal symptoms)

Chlorpromazine IV — Level C (May Offer)

• Dose: 12.5–25 mg IV
• Likely effective — similar efficacy to prochlorperazine and metoclopramide
• Downgraded due to higher rate of adverse effects (50% vs 21% for prochlorperazine)
• Adverse effects: Postural hypotension, sedation, akathisia

Other Dopamine Receptor Antagonists — Level C (May Offer)

• Droperidol 2.75–8.25 mg IM: May offer when prochlorperazine/metoclopramide unavailable (note FDA boxed warning for dose-dependent QT prolongation — obtain ECG and avoid with baseline QT prolongation)
• Haloperidol 5 mg IV: May offer when prochlorperazine/metoclopramide unavailable
• Trimethobenzamide IM: Level U — insufficient evidence
• Parenteral promethazine: Level U — no studies met inclusion criteria despite common use

2. NSAIDs

Dexketoprofen IV — Level B (Should Offer)

• Dose: 50 mg IV
• Highly likely effective — multiple class I studies, superior to placebo
• Combination with metoclopramide 10 mg IV provides enhanced benefit (class I evidence)
• No serious adverse effects reported

Ketorolac IV — Level B (Should Offer)

• Dose: 30–60 mg IV
• Likely effective — superior to valproate, comparable to metoclopramide
• No serious adverse effects

Other NSAIDs

• Acetylsalicylic acid 0.5–1.8 g IV: Level C — may offer
• Diclofenac 75 mg IM: Level C — may offer
• Ibuprofen 400–800 mg IV: Level U — conflicting class I studies (negative placebo trial but comparable to dexketoprofen)

3. Triptans

Sumatriptan SC — Level B (Should Offer)

• Dose: 3–6 mg SC
• Highly likely effective — multiple positive placebo-controlled trials
• Most effective when administered while pain is still mild (within 1–2 hours of onset)
• Did not receive Level A due to inferiority to prochlorperazine
• Can be prescribed at discharge for home use
• Adverse effects: Chest pain, palpitations, flushing (triptan sensations)
• Contraindications: Serious cardiovascular disease

4. CGRP Monoclonal Antibodies

Eptinezumab IV — Level U (No Recommendation for General ED Use)

• Dose: 100 mg IV
• Likely effective based on class I evidence (headache freedom at 2h: 23.5% vs 12.0% placebo)
• Level B (Should Offer) only for patients matching clinical trial population:
  • 4–15 monthly migraine days
  • Prior or current triptan use
  • 24 hours headache freedom before treated attack
  • Active contraception use, no pregnancy risk
• Barriers to ED use: High cost, prior authorization requirements, 6-month washout for pregnancy
• ED-specific studies needed for broader recommendation

5. Nerve Blocks

Greater Occipital Nerve Blocks (GONB) — Level A (Must Offer)

• Technique: 0.5–3 mL of 0.5% bupivacaine or 1% lidocaine, bilateral
• Highly likely effective — three positive class I studies
• Comparable to metoclopramide IV; superior to sham
• Provider experience matters — better outcomes with ≥7 prior procedures
• Adverse effects: Injection site pain only

Supraorbital Nerve Blocks (SONB) — Level B (Should Offer)

• Technique: 0.25 mL of 1% lidocaine
• Likely effective, especially in combination with GONB
• GONB alone or GONB+SONB superior to SONB alone

Sphenopalatine Ganglion (SPG) Blocks — Level U (No Recommendation)

• Modest benefit in class II study, but performed in outpatient chronic migraine population
• Commercial intranasal kits carry significant costs
• ED-specific studies needed

6. Corticosteroids

Dexamethasone IV — Level C (May Offer) for Acute Pain

• Dose: 8–16 mg IV
• Possibly effective for acute pain — comparable to valproate
• Level B (Should Offer) for preventing attack recurrence — unchanged from 2016
• Caution with cumulative corticosteroid exposure
• No serious adverse effects

7. Opioids

Other Opioids

• Morphine 0.1 mg/kg IV: Level C — May NOT offer
• Meperidine IV: Level U — insufficient evidence
• Nalbuphine IV: Level U — no studies despite common use (>5% of ED migraine visits)
• Tramadol IV: Level U — insufficient evidence

8. General Anesthetics

Ketamine IV — Level U (No Recommendation)

• Dose studied: 0.08–0.2 mg/kg IV
• Negative class II placebo-controlled trial, positive class III trial
• Low dose possibly ineffective; prolonged infusion during admission not assessed
• Adverse effects: Transient insobriety, fatigue

Propofol IV — Level U (No Recommendation)

• Likely ineffective — negative class I placebo-controlled trial
• Concerns about masking due to sedation
• Short duration of benefit
• Adverse effects: Sedation, bradykinesia, hypotension; rare risk of propofol infusion syndrome

9. Miscellaneous Treatments

Valproate IV — Level C (May Offer)

• Dose: 400–1000 mg IV
• Possibly effective — inferior to ketorolac and metoclopramide but comparable to dexamethasone
• Doses ≥800 mg may perform better
• No serious adverse effects

Other Miscellaneous Agents

• Dipyrone 1000 mg IV: Level C — may offer (positive class II placebo-controlled trial)
• Caffeine 60 mg IV: Level U — similar to ketorolac in class II study
• Granisetron 2 mg IV: Level U — only class III evidence
• Lidocaine IV (bolus + infusion): Level U — conflicting class II studies
• Normal saline 1L over 1h: Level U — possibly ineffective; may be appropriate if dehydration present
• Magnesium 1000–2000 mg IV: Level U — may be considered in patients with aura
• Dihydroergotamine IV/SC: Level U — classic Raskin protocol not evaluated

Agents NOT Recommended

• Paracetamol/acetaminophen 1000 mg IV: Level C — May NOT offer (negative class I placebo-controlled trial)
• Diphenhydramine 50 mg IV: Level C — May NOT offer for acute pain relief (but useful for akathisia)
• Octreotide 0.1 mg SC: Level C — May NOT offer

10. Treatment Algorithm Summary

11. Key Evidence Comparison Table

12. Special Considerations

Combination Therapy

• Metoclopramide 10 mg IV + dexketoprofen 50 mg IV: Superior to either alone (class I)
• Prochlorperazine + diphenhydramine: Reduces akathisia, effective combination
• GONB + SONB: Combined approach superior to SONB alone

Patient Selection Factors

• Cardiovascular disease: Avoid sumatriptan
• NSAID contraindications: Use dopamine antagonists or nerve blocks
• Extrapyramidal symptom risk: Consider nerve blocks; use diphenhydramine prophylaxis
• Early in attack (mild pain): Triptans most effective
• Dehydration from vomiting: IV fluids appropriate adjunct
• Migraine with aura: Magnesium may be considered

Time to Treatment Outcome

• Most studies use 1-hour primary outcome (recommended for ED parenteral treatment trials)
• IHS guidelines recommend 2-hour outcomes, but parenteral treatments have faster onset
• Some patients request discharge before 2-hour assessment

Reference

Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr SL. 2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2026;66:53-76. doi:10.1111/head.70016