What is a good headache cocktail?

Optimal Headache Cocktail for Acute Treatment

The most effective headache cocktail for acute treatment combines NSAIDs (such as aspirin, ibuprofen, or naproxen) as first-line therapy for mild to moderate headaches, with triptans (such as sumatriptan or rizatriptan) for moderate to severe headaches, and antiemetics (such as metoclopramide or prochlorperazine) to address nausea and provide synergistic analgesia. 1, 2

First-Line Treatment Options

• NSAIDs are recommended as first-line treatment for mild to moderate migraine attacks due to their demonstrated efficacy and favorable tolerability profile 1, 2
• Specific NSAIDs with strong evidence include:
  • Aspirin (650-1000 mg)
  • Ibuprofen (400-800 mg)
  • Naproxen sodium (275-550 mg)
  • Combination medications containing acetaminophen, aspirin, and caffeine 2, 1
• For moderate to severe headaches, triptans (serotonin1B/1D agonists) are recommended as first-line therapy 1, 2
• Oral triptans with good evidence include:
  • Sumatriptan (50-100 mg)
  • Rizatriptan (5-10 mg)
  • Naratriptan
  • Zolmitriptan 2, 3, 4

Antiemetics and Adjunctive Treatments

• Antiemetics serve dual purposes in headache treatment:
  • Treating accompanying nausea/vomiting
  • Providing synergistic analgesia for headache pain 1, 5
• Metoclopramide (10 mg IV or oral) is effective not only for treating nausea but also provides additional pain relief 1, 5
• Prochlorperazine (10 mg IV or 25 mg oral) effectively relieves headache pain and has been shown to be comparable to metoclopramide in efficacy 1, 6
• Diphenhydramine (25-50 mg) is often added to prevent extrapyramidal side effects when using prochlorperazine 6

Combination Approaches

• The combination of a triptan plus an NSAID has demonstrated superior efficacy compared to either agent alone 7
• Sumatriptan-naproxen combination (50-85 mg sumatriptan with 500 mg naproxen sodium) has shown clear superiority over the isolated use of each agent 7
• Adding metoclopramide (10 mg) to sumatriptan has been shown to improve efficacy in triptan-nonresponsive migraineurs 5
• For IV treatment in emergency settings, a combination of ketorolac, metoclopramide or prochlorperazine, and fluid rehydration is highly effective 1

Important Considerations and Cautions

• Medication should be administered as early as possible in the headache phase for maximum effectiveness 6, 8
• If significant nausea or vomiting is present, consider non-oral routes of administration:
  • Subcutaneous or intranasal sumatriptan
  • Prochlorperazine suppositories
  • IV administration of antiemetics 2, 1, 6
• Avoid frequent use of acute medications (more than twice weekly) to prevent medication-overuse headache 1
• Triptans are contraindicated in patients with:
  • Risk for heart disease
  • Basilar or hemiplegic migraine
  • Uncontrolled hypertension 2
• Opioids should be reserved for when other medications cannot be used, when sedation effects are not a concern, or when the risk for abuse has been addressed 2, 1

Evidence-Based Algorithm for Headache Treatment

1. For mild to moderate headaches:

   • Start with NSAIDs: aspirin (650-1000 mg), ibuprofen (400-800 mg), or naproxen sodium (275-550 mg) 1, 6
   • Consider adding an antiemetic if nausea is present: metoclopramide (10 mg) 1, 8

2. For moderate to severe headaches or if NSAIDs are ineffective:

   • Use a triptan (sumatriptan 50-100 mg or rizatriptan 5-10 mg) 2, 3, 4
   • Consider combining with an NSAID for enhanced efficacy 7
   • Add an antiemetic (metoclopramide or prochlorperazine) for nausea and additional analgesia 1, 5

3. For severe, refractory headaches in emergency settings:

   • IV ketorolac (30 mg)
   • IV metoclopramide (10 mg) or prochlorperazine (10 mg)
   • IV fluid rehydration
   • Consider IV dihydroergotamine (DHE) if the above fail 1, 2

The evidence clearly supports using combination therapy targeting multiple mechanisms for more effective headache relief, with the specific components tailored to headache severity and associated symptoms.