What are the typical ingredients and doses of a migraine cocktail administered intramuscularly (IM) in adults?

Migraine Cocktail IM: Typical Ingredients and Doses

The most commonly used IM migraine cocktail consists of metoclopramide 10 mg IM combined with diphenhydramine 25-50 mg IM, though evidence suggests diphenhydramine may not add therapeutic benefit.

Primary Components

Metoclopramide (Antiemetic/Dopamine Antagonist)

• Dose: 10 mg IM 1
• This is the cornerstone medication, providing both anti-nausea and direct antimigraine effects 2
• Can be administered slowly IV over 1-2 minutes as an alternative route 1
• Metoclopramide combined with diphenhydramine was superior to NSAIDs and triptans in comparative studies 2

Diphenhydramine (Antihistamine)

• Dose: 25-50 mg IM 3, 4
• Traditionally added to prevent akathisia (restlessness) from metoclopramide 5
• However, a 2016 randomized trial demonstrated that diphenhydramine provides no additional benefit for migraine relief when combined with metoclopramide 5
• Maximum daily dose is 400 mg for adults 3
• Despite lack of efficacy data, it remains commonly used in practice for dystonic reaction prophylaxis 2

Alternative IM Cocktail Components

Ketorolac (NSAID)

• Dose: 30-60 mg IM (standard adult dosing)
• NSAIDs were generally well-tolerated and may provide benefit even when given late in the migraine attack 2
• Injectable NSAIDs are reasonable second-line options when first-line treatments fail 6
• Ketorolac was the most frequently studied NSAID in the emergent setting 2

Corticosteroids (for Recurrence Prevention)

• Dexamethasone 10-20 mg IM or methylprednisolone 1-2 mg/kg IM 7
• Steroids afford protection against headache recurrence after discharge, which can exceed 50% within 24-72 hours 2
• Should be considered as adjunctive therapy rather than primary treatment 2

Important Clinical Considerations

What NOT to Include

• Opioids (meperidine) should be avoided despite historical use 2, 6
• Meperidine was inferior to dopamine antagonists and provides no advantage over other options 2
• Most opioids have been shown to be inefficacious for migraine, with the exception of nalbuphine 6

Monitoring Requirements

• Monitor for akathisia and dystonic reactions with metoclopramide 1
• If acute dystonic reactions occur, administer diphenhydramine 50 mg IM 1
• The American Academy of Pediatrics recommends monitoring oxygen saturation when using sedating medications, though this applies primarily to benzodiazepines 8, 9

Practical Algorithm

1. First-line IM cocktail: Metoclopramide 10 mg IM alone 1, 5
2. If akathisia is a concern: Add diphenhydramine 25-50 mg IM (for prophylaxis, not efficacy) 3, 5
3. If inadequate response: Add ketorolac 30-60 mg IM 6
4. For recurrence prevention: Add dexamethasone 10-20 mg IM before discharge 2

Common Pitfalls

• Avoid reflexively adding diphenhydramine - it does not improve migraine outcomes and only serves to prevent dystonic reactions 5
• Do not use opioid-based cocktails (meperidine/promethazine combinations) as they are inferior to dopamine antagonists 2, 6
• Recognize that combination therapy is common in practice but individual medication efficacy is often difficult to determine due to lack of placebo-controlled comparisons 2