Migraine Cocktail Dosing
For acute migraine in the emergency department, administer metoclopramide 10 mg IV as the primary agent, ketorolac 60 mg IM as the NSAID component, and avoid diphenhydramine as it provides no additional benefit. 1, 2
Metoclopramide (Reglan) Dosing
- Administer 10 mg IV or orally as the standard dose for acute migraine 1
- Higher doses (20 mg or 40 mg) provide no additional benefit over 10 mg and carry the same side effect profile 2
- Give 20-30 minutes before or with an NSAID for optimal gastric motility improvement 1
- Contraindications include: pheochromocytoma, seizure disorder, GI bleeding, and GI obstruction 1
- Common adverse effects: restlessness, drowsiness, diarrhea, muscle weakness, and dystonic reactions 1
- Akathisia occurs in approximately 9% of patients receiving metoclopramide regardless of dose 2
Ketorolac (Toradol) Dosing
- Administer 60 mg IM as the standard dose 1
- Can repeat every 15-30 minutes if needed 1
- Maximum daily dose is 120 mg 1
- Do not exceed 5 days of treatment 1
- Contraindications include: aspirin/NSAID-induced asthma, pregnancy, and cerebrovascular hemorrhage 1
- Ketorolac provides faster initial pain reduction (within 1 hour) compared to metoclopramide combinations, though final outcomes at 2 hours are equivalent 3
Diphenhydramine (Benadryl): Not Recommended
- Do not routinely add diphenhydramine 25-50 mg to the migraine cocktail 4
- A high-quality 2016 randomized trial demonstrated that diphenhydramine added to metoclopramide provides no improvement in sustained headache relief (40% vs 37%, 95% CI -10% to 16%) 4
- Diphenhydramine does not reduce akathisia rates when added to metoclopramide 4
- The historical practice of adding diphenhydramine lacks evidence-based support 4
Adjunctive Dexamethasone Dosing
- Add dexamethasone 4 mg IV to reduce headache recurrence after ED discharge 5
- Higher doses (16 mg) provide no additional benefit over 4 mg (sustained relief 34% vs 41%, 95% CI -6% to 20%) 5
- Dexamethasone is particularly useful for preventing recurrent or protracted migraine 1
Clinical Implementation Algorithm
Step 1: Administer metoclopramide 10 mg IV as the primary agent 2
Step 2: Add ketorolac 60 mg IM for NSAID effect 1, 3
Step 3: Add dexamethasone 4 mg IV to prevent recurrence 5
Step 4: Reassess pain at 1-2 hours; expect mean improvement of 4.7 points on 0-10 scale 2
Step 5: If inadequate response, consider migraine-specific agents (triptans) rather than increasing doses 1
Important Caveats
- Avoid medication overuse: Limit acute treatment to no more than twice weekly to prevent medication-overuse headaches 1
- Dystonia prophylaxis is unnecessary: The routine addition of diphenhydramine for dystonia prevention is not evidence-based 4
- Monitor for akathisia: This occurs in approximately one-third of patients receiving metoclopramide and is not dose-dependent 2
- Alternative NSAID options: If ketorolac is contraindicated, consider ibuprofen 800 mg or naproxen sodium 550 mg orally 1
- Prochlorperazine alternative: If metoclopramide is contraindicated, prochlorperazine 25 mg orally or suppository can be used (maximum 3 doses per 24 hours) 1