What is a good headache cocktail?

Optimal Headache Cocktail for Acute Migraine

For moderate to severe migraine in the emergency or urgent care setting, the most effective headache cocktail is IV metoclopramide 10 mg plus IV ketorolac 30 mg, which provides rapid pain relief while minimizing side effects and risk of rebound headache. 1

First-Line IV Cocktail Components

Primary Combination:

• Metoclopramide 10 mg IV - Provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic action 1, 2
• Ketorolac 30 mg IV (60 mg IM for patients under 65) - Rapid onset with approximately 6 hours duration, minimal rebound headache risk 1, 2

This combination addresses both the pain and nausea components synergistically, with metoclopramide enhancing absorption and providing independent analgesic benefit beyond its antiemetic properties 1.

Alternative IV Options

If NSAIDs are contraindicated:

• Prochlorperazine 10 mg IV - Comparable efficacy to metoclopramide with 21% adverse event rate versus 50% with chlorpromazine 1
• Dihydroergotamine (DHE) nasal spray or IV - Good evidence for efficacy as monotherapy 2

For severe refractory cases:

• Consider adding subcutaneous sumatriptan 6 mg - Fastest onset (15 minutes to peak), 70-82% response rate 1, 3

Oral Outpatient Cocktail

For patients treating at home with moderate to severe migraine:

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg - Superior to either agent alone with high-certainty evidence 2
  • 130 more patients per 1000 achieve sustained pain relief at 48 hours versus triptan alone 2
  • 90 more patients per 1000 achieve pain relief at 2 hours versus triptan alone 2

Alternative oral combination:

• Rizatriptan 10 mg PLUS acetaminophen 1000 mg - May provide benefit, though evidence is lower quality than sumatriptan/naproxen combination 2

Critical Frequency Limitation

Limit ALL acute migraine medications to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 1, 2. If patients require treatment more than twice weekly, initiate preventive therapy immediately with propranolol, topiramate, or amitriptyline 1.

Medications to AVOID in Headache Cocktails

• Opioids (hydromorphone, meperidine, oxycodone) - Lead to dependency, rebound headaches, and loss of efficacy 1, 4
• Diphenhydramine - No evidence for migraine efficacy, adds unnecessary sedation 1
• Prednisone/corticosteroids - Limited evidence for acute treatment; more appropriate for status migrainosus 1

Dosing Algorithm by Setting

Emergency Department/Urgent Care:

1. Start with metoclopramide 10 mg IV + ketorolac 30 mg IV 1
2. If inadequate response at 30-60 minutes, add prochlorperazine 10 mg IV 1
3. For persistent severe pain, consider subcutaneous sumatriptan 6 mg 1, 3

Outpatient/Home Treatment:

1. Mild-moderate migraine: Naproxen 500-825 mg alone 2, 5
2. Moderate-severe migraine: Sumatriptan 50-100 mg + naproxen 500 mg 2
3. With significant nausea: Add metoclopramide 10 mg PO 20-30 minutes before other medications 2

Common Pitfalls to Avoid

• Do not restrict metoclopramide only to vomiting patients - Nausea itself is disabling and warrants treatment 1
• Do not combine triptans with ergotamines - Risk of prolonged vasospasm 2
• Avoid triptans in patients with uncontrolled hypertension, ischemic heart disease, or hemiplegic/basilar migraine 2, 6
• Reduce ketorolac dose to 15 mg IV in patients ≥65 years or with renal impairment 1

Contraindications Requiring Alternative Approach

Ketorolac contraindications:

• Active GI bleeding, renal impairment (CrCl <30), aspirin/NSAID-induced asthma 1

Triptan contraindications:

• Ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, significant cardiovascular disease 2

Metoclopramide/Prochlorperazine contraindications:

• Pheochromocytoma, seizure disorder, GI obstruction, CNS depression 2