What is the composition of a migraine cocktail for acute migraine treatment?

Migraine Cocktail for Acute Migraine Treatment

The standard migraine cocktail for acute migraine treatment in the emergency department consists of intravenous NSAIDs as first-line therapy, followed by prochlorperazine 10 mg IV with diphenhydramine 25 mg IV as second-line therapy, and triptans as third-line options. 1

First-Line Treatment Components

• NSAIDs: The American College of Neurology recommends intravenous NSAIDs as first-line therapy 1
  • Ibuprofen 400-800 mg IV
  • Diclofenac potassium IV
  • Acetylsalicylic acid (ASA) IV
  • For oral administration: ibuprofen 400-800mg or naproxen sodium 275-550mg

NSAIDs have demonstrated efficacy and favorable tolerability, making them appropriate first-line treatments for all migraine attacks, including severe ones that have previously responded to NSAIDs 2.

Second-Line Treatment Components

• Antiemetic + Antihistamine: The American Academy of Neurology strongly recommends prochlorperazine 10 mg IV with diphenhydramine 25 mg IV as second-line therapy 1
  • Prochlorperazine has superior efficacy to subcutaneous sumatriptan in ED treatment of migraine
  • Metoclopramide (10 mg IV) is an alternative antiemetic with dual antiemetic and antimigraine properties 1
  • Diphenhydramine is added to prevent extrapyramidal side effects

Research supports metoclopramide's efficacy, with studies showing that 10 mg IV is as effective as higher doses (20 mg or 40 mg) with fewer side effects 3. Similarly, a randomized controlled trial found that prochlorperazine 10 mg IV and metoclopramide 20 mg IV (both with diphenhydramine 25 mg IV) were equally efficacious for acute migraine treatment 4.

Third-Line Treatment Components

• Triptans: Recommended when NSAIDs and dopamine antagonists fail or are contraindicated 1
  • Sumatriptan 6 mg subcutaneous (fastest onset)
  • Oral options: rizatriptan, zolmitriptan, naratriptan
  • Intranasal sumatriptan is an option for patients with nausea and vomiting

Triptans have good evidence for effectiveness but come with contraindications including cardiovascular disease, uncontrolled hypertension, and basilar or hemiplegic migraine 2, 1.

Additional Components Sometimes Added

• Dihydroergotamine (DHE): Intranasal DHE has good evidence for efficacy and safety as monotherapy 2
• Corticosteroids: May be used for status migrainosus, though evidence is inconsistent 5
• Magnesium: IV magnesium may be beneficial in migraine with aura 6

Important Contraindications and Precautions

• Triptans: Avoid in patients with:

  • Uncontrolled hypertension
  • Cardiovascular disease or risk factors
  • Basilar or hemiplegic migraine
  • Recent use of ergotamine-type medications (within 24 hours)
  • Use of MAOIs or other triptans within 24 hours 1

• NSAIDs: Contraindicated in:

  • Aspirin/NSAID-induced asthma
  • Bleeding disorders
  • G6PD deficiency (for aspirin) 1

• Antiemetics: Monitor for:

  • Extrapyramidal symptoms with prochlorperazine
  • Sedation, especially with antihistamine combinations
  • Potential QT prolongation 1

Practical Application Algorithm

1. Start with first-line therapy: IV NSAIDs (ibuprofen 400-800 mg, diclofenac, or ASA)
2. If inadequate response after 30 minutes, add second-line therapy: Prochlorperazine 10 mg IV + diphenhydramine 25 mg IV
3. If still inadequate response after 30 minutes, consider third-line therapy: Sumatriptan 6 mg subcutaneous (if no contraindications)
4. For status migrainosus: Consider adding corticosteroids

Common Pitfalls to Avoid

• Overuse of opioids: Despite butorphanol nasal spray showing efficacy, opioids should be reserved for when other medications cannot be used due to concerns about dependence 2, 6
• Inadequate antiemetic coverage: Nausea and vomiting are common migraine symptoms that can impair oral medication absorption
• Neglecting to prevent medication side effects: Always co-administer diphenhydramine with neuroleptics to prevent extrapyramidal symptoms
• Using ineffective treatments: Intranasal lidocaine, butalbital combinations, and octreotide have inadequate evidence or are proven ineffective 6

The composition of the migraine cocktail should be tailored based on the severity of the attack, associated symptoms, and the patient's previous response to specific medications, with careful attention to contraindications.