What is in a common migraine cocktail?

Common Migraine Cocktail Components

A standard migraine cocktail in acute care settings consists of IV ketorolac 30 mg combined with either IV metoclopramide 10 mg or IV prochlorperazine 10 mg, with IV dihydroergotamine (DHE) reserved for refractory cases. 1, 2, 3

Core Injectable Components

NSAID Component

• Ketorolac 30 mg IV serves as the foundational analgesic, providing rapid onset with approximately 6 hours of duration and minimal rebound headache risk 1, 2, 3
• For patients under 65 years without renal impairment, use 30 mg IV or 60 mg IM 2, 3
• Reduce dose for patients ≥65 years or with renal impairment 3

Antiemetic/Adjunctive Component

• Metoclopramide 10 mg IV provides both antiemetic effects and direct analgesic properties through central dopamine receptor antagonism, offering synergistic pain relief beyond just treating nausea 1, 2, 3
• Prochlorperazine 10 mg IV represents an equally effective alternative that relieves headache pain comparably to metoclopramide, with a slightly more favorable side effect profile (21% vs 50% adverse events compared to chlorpromazine) 1, 2, 3

Refractory Cases

• Dihydroergotamine (DHE) 1 mg IV should be added for inadequate response after 30-60 minutes 2, 3
• DHE has good evidence for efficacy and safety as monotherapy for severe migraines 4, 2

Alternative Oral "Cocktail" Formulations

Combination Analgesics

• Aspirin 250 mg + acetaminophen 250 mg + caffeine 65 mg provides synergistic analgesia, with caffeine enhancing absorption and efficacy of the analgesics 4, 2, 3
• This combination has Level A evidence for efficacy in acute migraine treatment 4

Triptan-NSAID Combinations

• Sumatriptan 50-100 mg + naproxen 500 mg demonstrates superior efficacy compared to either agent alone, with 180 more patients per 1000 achieving sustained pain relief at 48 hours 4, 3
• This combination is the American College of Physicians' strongest recommendation for moderate to severe migraine 4

Single-Agent Alternatives

• Naproxen sodium 500-825 mg can be used as monotherapy for mild to moderate attacks 4, 3
• Ibuprofen 400-800 mg has good evidence as first-line therapy 4, 2

Administration Strategy and Timing

• Begin treatment as early as possible during the attack to improve efficacy, ideally when pain is still mild 4, 1, 3
• Administer antiemetic 20-30 minutes before or with other medications to enhance absorption and treat gastric stasis 1, 3
• Assess response after 30-60 minutes 2, 3
• For inadequate response, add DHE 1 mg IV or consider subcutaneous sumatriptan 6 mg if DHE is contraindicated 2, 3

Critical Contraindications

Absolute Contraindications to Triptans and DHE

• Ischemic coronary artery disease, coronary artery vasospasm, or Prinzmetal's angina 4, 5
• Uncontrolled hypertension 4, 5
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders 5
• History of stroke, TIA, hemiplegic or basilar migraine 5
• Peripheral vascular disease or ischemic bowel disease 5
• Recent use (within 24 hours) of another triptan or ergot-containing medication 5

Ketorolac Cautions

• Use with caution in renal impairment (creatinine clearance <30 mL/min), history of GI bleeding, or heart disease 1, 3

Medications to Avoid

• Opioids (hydromorphone, oxycodone, butorphanol) should be avoided as they lead to dependency, rebound headaches, and eventual loss of efficacy, with limited evidence supporting their use for migraine 4, 1, 3
• Opioids should only be reserved for cases where other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 4

Medication Overuse Headache Prevention

• Limit acute therapy to no more than twice weekly to prevent medication-overuse headache, which can result from frequent use and lead to daily headaches 4, 1, 2, 3
• If patients require acute treatment more than 2 days per week, transition to preventive therapy rather than increasing frequency of acute medications 1, 3
• Do not allow patients to escalate acute medication frequency in response to treatment failure—this creates a vicious cycle of medication-overuse headache 1, 3

Route-Specific Considerations

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) when significant nausea or vomiting is present, though with higher adverse event rates 3
• Intranasal formulations (sumatriptan 5-20 mg or DHE nasal spray) offer alternatives for patients who cannot tolerate oral medications 4, 3

Common Pitfalls to Avoid

• Do not restrict metoclopramide only to vomiting patients—nausea itself is one of the most disabling symptoms and warrants treatment even without vomiting 1, 3
• Do not use prednisone or corticosteroids routinely—they have limited evidence for acute headache treatment and are more appropriate for status migrainosus 1
• Triptans are most effective when taken early in the attack while headache is still mild, not after pain becomes severe 4, 1