New Emergency Department Migraine Treatment Guidelines

Posted on January 14 2026, By: Cerebral Torque

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2025 AHS Guidelines: Acute Migraine Treatment in the Emergency Department

Overview: A Landmark Update in ED Migraine Care

The American Headache Society (AHS) has released its 2025 guideline update for the acute treatment of migraine in adults presenting to the emergency department. This update, published in Headache in 2025, builds upon the 2016 guideline and incorporates evidence from 26 new randomized controlled trials encompassing over 3,000 additional participants.

Migraine remains a leading cause of headache-related ED visits, accounting for approximately one-fourth of the 3.5 million annual headache-related visits in the United States. Despite existing guidelines, significant variability persists in ED migraine management, and clinical outcomes remain suboptimal - only 37.3% of patients achieve headache freedom at discharge.

New RCTs Reviewed

Including 13 Class I studies with low risk of bias

3,019

Additional Participants

Adding to the evidence base from 2016

New Level A Treatments

Prochlorperazine IV and greater occipital nerve blocks

Key Changes from the 2016 Guidelines

The most significant updates include the elevation of prochlorperazine IV and greater occipital nerve blocks (GONB) to Level A (must offer) status, the downgrading of hydromorphone IV to Level A (must NOT offer), and the addition of supraorbital nerve blocks to the treatment protocols. Several treatments have also been upgraded or downgraded based on new evidence.

Level A Recommendations: Must Offer

For the first time, the AHS guidelines include Level A "must offer" recommendations for acute migraine treatment in the ED. These treatments have the strongest evidence supporting their use and should be offered to eligible adults without contraindications.

Must Offer to Eligible Patients

Prochlorperazine 10-12.5 mg IV must be offered to adults presenting with a migraine attack in the ED for treatment of headache requiring parenteral therapy in those without contraindications.

Greater Occipital Nerve Blocks (GONB) using 0.5-3 mL of 0.5% bupivacaine or 1% lidocaine must be offered to adults presenting with a migraine attack in the ED with no local anesthetic or local injection contraindications.

Why These Treatments Earned Level A Status

Prochlorperazine IV

Multiple high-quality studies demonstrate superiority to opioids and non-inferiority to other effective agents. A class I study showed prochlorperazine plus diphenhydramine was significantly better than hydromorphone, with 86% experiencing mild or no pain at 1 hour compared to 52% with hydromorphone. Common side effects include akathisia and sedation, which can be treated with diphenhydramine.

Greater Occipital Nerve Blocks

Three positive class I studies support GONB efficacy, including two studies showing superiority versus sham procedure. In one study, 31% achieved headache freedom at 30 minutes with GONB compared to 0% with sham. Notably, provider experience improves outcomes - clinicians with seven or more prior nerve blocks achieved better results.

Level B Recommendations: Should Offer

Level B treatments have strong evidence supporting their use and should be offered when clinically appropriate. Several treatments in this category have been upgraded from the 2016 guidelines based on new evidence.

Level B - Should Offer

Dexketoprofen 50 mg IV Upgraded from Level C

Ketorolac 30-60 mg IV Upgraded from Level C

Metoclopramide 10 mg IV Maintained

Sumatriptan 3-6 mg SC Maintained

Supraorbital Nerve Blocks (SONB) New Addition

Clinical Considerations for Level B Treatments

Dexketoprofen showed benefit in multiple class I studies and may provide enhanced benefits when combined with metoclopramide. Ketorolac performed better than valproate and similar to metoclopramide in class I evidence. Sumatriptan SC remains highly effective, especially when used early in the attack while pain is mild, and has the advantage of being prescribable for home use. SONB should ideally be performed in combination with GONB for optimal results.

Level C Recommendations: May Offer

Level C treatments have supportive evidence and may be considered when higher-level treatments are not appropriate or available. These should be selected based on individual patient factors and clinical circumstances.

Level C - May Offer

Acetylsalicylic acid 0.5-1.8 g IV For NSAID-eligible patients

Chlorpromazine 12.5-25 mg IV Higher adverse effect rate

Dexamethasone 8-16 mg IV Upgraded from Level U

Diclofenac 75 mg IM For NSAID-eligible patients

Dipyrone 1000 mg IV Regional availability

Droperidol 2.75-8.25 mg IM Monitor for EPS

Haloperidol 5 mg IV Monitor for EPS

Valproate 400-1000 mg IV Higher doses may work better

Important Note on Dexamethasone

While dexamethasone received a Level C recommendation for acute pain relief, it maintains a separate Level B recommendation specifically for preventing headache recurrence after ED discharge. Caution is warranted regarding potential cumulative corticosteroid exposure in patients who receive frequent ED treatment.

Treatments to Avoid

The guidelines now include the first-ever Level A "must NOT offer" recommendation, reflecting strong evidence against the use of certain treatments in the ED migraine population.

Level A - Must NOT Offer

Hydromorphone 1 mg IV must NOT be offered to adults presenting with a migraine attack in the ED under most circumstances. Very select potential exceptions may include patients with no alternative treatment options and stable prior opioid response with low risk of dependence or medication-overuse headache.

Level C - May NOT Offer

Diphenhydramine 50 mg IV Ineffective for pain relief

Morphine 0.1 mg/kg IV Inferior outcomes

Octreotide 0.1 mg SC Insufficient benefit

Paracetamol/Acetaminophen 1000 mg IV Downgraded from Level C

The downgrade of IV paracetamol/acetaminophen from Level C (may offer) to Level C (may NOT offer) is notable. A negative class I placebo-controlled study demonstrated it was inferior to placebo, leading to this reclassification.

Nerve Blocks: A Major Addition to the Guidelines

One of the most significant updates in the 2025 guidelines is the formal inclusion of nerve blocks as treatment options. This represents a new frontier in ED migraine management with strong supporting evidence.

Level A

Greater Occipital Nerve Blocks

Must offer with 0.5% bupivacaine or 1% lidocaine

Level B

Supraorbital Nerve Blocks

May offer, best combined with GONB

Level U

Sphenopalatine Ganglion Blocks

Insufficient ED-specific evidence

GONB Evidence Summary

Three class I studies and one class II study support the use of GONB. Key findings include headache freedom at 30 minutes in 31% of patients versus 0% with sham procedure in treatment-refractory patients. When performed by experienced providers (seven or more prior injections), pain improvement increased significantly. GONB performed similarly to metoclopramide IV and better than sham procedure.

Practical Considerations for Nerve Blocks

GONB Technique: Bilateral injection of 0.5-3 mL of 0.5% bupivacaine or 1% lidocaine at the greater occipital nerve.

SONB Technique: Injection of 0.25 mL of 1% lidocaine at the supraorbital nerve; best performed in combination with GONB.

Safety: Monitor total injected dose to prevent local anesthetic systemic toxicity. No severe adverse effects were reported in trials.

Provider Experience: Outcomes improve with provider experience - consider training programs to optimize results.

Dopamine Receptor Antagonists: The Cornerstone of ED Treatment

Dopamine receptor antagonists remain central to ED migraine management, with prochlorperazine achieving the highest recommendation level. These medications address both pain and the common accompanying symptoms of nausea and vomiting.

Dopamine Receptor Antagonist Recommendations

Medication	Dose	Level	Key Evidence	Adverse Effects
Prochlorperazine IV	10-12.5 mg	Level A - Must Offer	Superior to hydromorphone; similar to chlorpromazine; better than sumatriptan in Class I studies	Akathisia, sedation (treatable with diphenhydramine)
Metoclopramide IV	10 mg	Level B - Should Offer	Similar to GONB, dexketoprofen, sumatriptan, ketorolac; combination with dexketoprofen may enhance benefits	Akathisia
Chlorpromazine IV	12.5-25 mg	Level C - May Offer	Similar to prochlorperazine; better than placebo; higher adverse effect rate limits recommendation	Postural hypotension, sedation, akathisia (50% vs 21% with prochlorperazine)
Droperidol IM	2.75-8.25 mg	Level C - May Offer	Positive class II placebo-controlled study; similar to meperidine IM	Monitor for extrapyramidal symptoms
Haloperidol IV	5 mg	Level C - May Offer	No difference versus metoclopramide; positive class III placebo-controlled study	Highest risk of extrapyramidal symptoms among typical antipsychotics

Managing Extrapyramidal Symptoms

Akathisia and other extrapyramidal symptoms are the primary concerns with dopamine receptor antagonists. Risk factors include personal or family history of extrapyramidal symptoms, longer duration of use, younger age, and type of neuroleptic. Treatment options include diphenhydramine, benztropine, propranolol, 5-HT2A receptor antagonists, benzodiazepines, and vitamin B6. Consider pre-treatment with diphenhydramine when using prochlorperazine.

NSAIDs: Upgraded Evidence for Key Agents

Several NSAIDs have been upgraded in the 2025 guidelines based on new high-quality evidence. These medications offer effective alternatives for patients without NSAID contraindications.

NSAID Recommendations Summary

Dexketoprofen 50 mg IV Level B - Should Offer (Upgraded)

Ketorolac 30-60 mg IV Level B - Should Offer (Upgraded)

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 - No Recommendation

Dexketoprofen achieved highly likely effective status based on multiple class I studies showing benefit over placebo and equivalence to metoclopramide. Importantly, the combination of dexketoprofen with metoclopramide appeared to provide enhanced benefits compared to either agent alone. Ketorolac demonstrated superiority to valproate and equivalence to metoclopramide in class I evidence.

The evidence for IV ibuprofen remains mixed, with one class I study showing no difference from placebo and another showing equivalence to dexketoprofen. This inconsistency led to a Level U (no recommendation) classification pending further research.

Opioids: Strong Evidence Against Use

The 2025 guidelines provide the strongest-ever guidance against opioid use in ED migraine treatment. Hydromorphone IV received the first Level A "must NOT offer" recommendation in the history of these guidelines.

Why Opioids Should Be Avoided

Hydromorphone 1 mg IV was inferior to prochlorperazine plus diphenhydramine in a high-quality class I study. At 1 hour, only 52% of hydromorphone patients had mild or no pain compared to 86% with prochlorperazine. Hydromorphone was also associated with more adverse events, higher return rates, and lower sustained relief. Prolonged opioid use can lead to medication-overuse headache and increased frequency of recurrent ED visits.

Opioid Recommendations

Hydromorphone 1 mg IV Level A - Must NOT Offer

Morphine 0.1 mg/kg IV Level C - May NOT Offer

Meperidine IV Level U - No Recommendation

Nalbuphine IV Level U - No Recommendation

Tramadol IV Level U - No Recommendation

Very select potential exceptions for opioid use may include patients with no alternative treatment options and stable prior opioid response with low risk of dependence or medication-overuse headache. However, these situations should be rare given the multiple effective non-opioid alternatives now available.

Clinical Implications and Implementation

The 2025 guidelines provide clear direction for ED practitioners managing acute migraine. Implementation of these recommendations has the potential to significantly improve patient outcomes while reducing reliance on ineffective or harmful treatments.

Suggested Treatment Approach

First-line options: Prochlorperazine 10-12.5 mg IV (consider with diphenhydramine) OR greater occipital nerve blocks with 0.5% bupivacaine or 1% lidocaine.

Alternative options: Metoclopramide 10 mg IV, dexketoprofen 50 mg IV, ketorolac 30-60 mg IV, or sumatriptan 3-6 mg SC (especially early in attack).

Add-on consideration: Dexamethasone 8-16 mg IV to prevent headache recurrence.

Avoid: Hydromorphone, morphine, and IV paracetamol/acetaminophen for migraine pain relief.

Special Populations and Considerations

Patients with Severe Nausea/Vomiting

Parenteral routes bypass the GI tract, making all recommended treatments suitable. Dopamine receptor antagonists offer the additional benefit of antiemetic effects.

Early Presentation

Sumatriptan SC may be particularly effective when used within 1-2 hours of headache onset while pain is still mild. It can also be prescribed for home use upon discharge.

Risk of Extrapyramidal Symptoms

Consider nerve blocks or NSAIDs as first-line in patients with history of extrapyramidal symptoms or those at higher risk (younger patients, family history).

Frequent ED Visitors

Avoid opioids to prevent medication-overuse headache and escalating ED utilization. Consider dexamethasone for recurrence prevention.

Emerging Treatments and Future Directions

Several treatments received Level U (no recommendation) status due to insufficient ED-specific evidence, though some show promise for future consideration.

Eptinezumab: A Promising CGRP Antibody

Eptinezumab 100 mg IV showed benefit in a class I study, with 23.5% achieving headache freedom at 2 hours compared to 12% with placebo. However, the study population was highly selective (4-15 monthly migraine days, triptan experience, outpatient setting) and does not represent typical ED patients. It received Level B for patients matching the trial population but Level U for general ED use pending ED-specific studies. Additional considerations include high cost, prior authorization requirements, and a 6-month washout requirement for pregnancy planning.

Treatments Requiring Further Study (Level U)

Caffeine 60 mg IV Possibly effective; limited evidence

Ketamine 0.08-0.2 mg/kg IV Conflicting evidence

Lidocaine IV Conflicting class II studies

Magnesium 1000-2000 mg IV May benefit patients with aura

Normal Saline 1 L IV Possibly ineffective for pain relief

Propofol IV Likely ineffective; negative class I study

SPG Blocks Insufficient ED-specific evidence

Conclusions

The 2025 AHS guideline update provides important new direction for ED migraine management, with several key takeaways for clinical practice.

Must Offer

Prochlorperazine IV & GONB

First Level A "must offer" recommendations in guideline history

Must NOT Offer

Hydromorphone IV

First Level A "must NOT offer" recommendation

Should Offer

5 Level B Treatments

Dexketoprofen, ketorolac, metoclopramide, sumatriptan, SONB

Key Practice Points

Prochlorperazine IV and GONB should be the primary treatment options for eligible patients. Opioids, particularly hydromorphone, should be avoided in favor of effective non-opioid alternatives. IV paracetamol/acetaminophen is not recommended for migraine pain relief. Nerve blocks offer a valuable non-pharmacologic option with strong evidence, and provider training may improve outcomes. Consider combination therapy (e.g., dexketoprofen plus metoclopramide) for enhanced benefits, and use dexamethasone to prevent headache recurrence.

These guidelines mark a significant advance in evidence-based ED migraine care. Implementation of these recommendations, particularly the shift away from opioids and toward proven effective treatments like prochlorperazine and nerve blocks, has the potential to meaningfully improve outcomes for the millions of migraine patients who present to emergency departments each year.

Important Medical Disclaimer

This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment. Treatment decisions should be individualized based on patient-specific factors, contraindications, and clinical circumstances. Always consult current guidelines and local protocols when making treatment decisions.

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