What is a good headache cocktail to give in the Emergency Department (ED)?

Optimal ED Headache Cocktail

For acute migraine in the ED, administer IV metoclopramide 10 mg plus IV ketorolac 30 mg as your first-line combination therapy, which provides rapid pain relief while minimizing side effects and rebound headache risk. 1

First-Line IV Cocktail Components

Metoclopramide 10 mg IV

• Provides direct analgesic effects through central dopamine receptor antagonism, offering independent pain relief beyond antiemetic properties 1
• Works synergistically with NSAIDs to enhance overall efficacy 1
• Addresses gastric stasis during migraine attacks, improving absorption of co-administered medications 1

Ketorolac 30 mg IV (60 mg IM if IV access unavailable)

• Delivers relatively rapid onset with approximately 6 hours duration 1
• Carries minimal risk of rebound headache compared to opioids 1
• Use reduced doses (15 mg IV) for patients ≥65 years or with renal impairment 1

Alternative IV Options When First-Line Fails or Is Contraindicated

Prochlorperazine 10 mg IV

• Comparable efficacy to metoclopramide with potentially fewer side effects 1
• Can be substituted when metoclopramide is contraindicated 1
• Contraindications: CNS depression, concurrent adrenergic blocker use, pheochromocytoma, seizure disorder 1

Dihydroergotamine (DHE) IV

• Good evidence for efficacy as monotherapy when dopamine antagonists or NSAIDs are contraindicated 1, 2
• Particularly useful for patients with cardiovascular contraindications to triptans 2

Critical Pitfalls to Avoid

Do NOT Routinely Add Diphenhydramine

• High-quality evidence demonstrates diphenhydramine provides no additional analgesic benefit when combined with metoclopramide 3
• A 2016 randomized controlled trial showed 40% sustained relief with metoclopramide + diphenhydramine versus 37% with metoclopramide + placebo (no significant difference) 3
• Diphenhydramine may only be justified to prevent akathisia in patients with prior history of this side effect with dopamine antagonists 4

Avoid Opioids as First-Line Therapy

• Opioids should be reserved only when other medications cannot be used, sedation is acceptable, and abuse risk has been addressed 1
• Lead to dependency, rebound headaches, and eventual loss of efficacy 1
• Meperidine was inferior to chlorpromazine and only equivalent to other dopamine antagonists in comparative studies 5

Limit Frequency to Prevent Medication-Overuse Headache

• Restrict all acute migraine medications to no more than 2 days per week 1
• Using acute treatments more than twice weekly creates a vicious cycle leading to daily headaches 1
• If patients require ED visits more frequently, initiate preventive therapy immediately 1

Adjunctive Considerations

IV Dexamethasone for Recurrence Prevention

• Consider adding dexamethasone to reduce headache recurrence after ED discharge 4
• Particularly useful given that headache recurrence rates can exceed 50% within 24-72 hours 5

IV Magnesium Sulfate 1-2g

• May be administered over 15-20 minutes for severe attacks not responding to first-line therapy 6
• Evidence is mixed, but may provide benefit in refractory cases 6
• Monitor for flushing and light-headedness 6

Contraindications Requiring Alternative Approach

Metoclopramide Contraindications

• Pheochromocytoma, seizure disorder, GI bleeding, GI obstruction 1

Ketorolac Contraindications

• Renal impairment (CrCl <30 mL/min), aspirin/NSAID-induced asthma, active GI bleeding 1
• History of cardiovascular disease requires caution 1

When to Escalate Beyond Standard Cocktail

If the standard metoclopramide + ketorolac combination fails after 60 minutes:

• Consider adding IV DHE for refractory cases 1, 2
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) if no cardiovascular contraindications exist 2
• Avoid combining triptans with ergotamines within 24 hours 7