What is the best course of treatment for a patient with a headache accompanied by nausea and vomiting, considering potential migraines and other underlying conditions?

Treatment of Headache with Nausea and Vomiting

For a patient presenting with headache accompanied by nausea and vomiting, start with combination therapy of a triptan plus NSAID along with a prokinetic antiemetic (metoclopramide or prochlorperazine), using non-oral routes when vomiting is present. 1

Initial Assessment: Rule Out Secondary Headaches

Before treating as migraine, screen for red flags requiring urgent evaluation 1:

• Thunderclap headache suggests subarachnoid hemorrhage 1
• Fever with neck stiffness indicates possible meningitis 1
• Progressive headache or focal neurological symptoms suggests intracranial space-occupying lesion 1
• New onset headache at age >50 years warrants consideration of temporal arteritis 1
• Headache brought on by coughing, sneezing, or exercise suggests intracranial pathology 1

If red flags are absent, proceed with migraine treatment algorithm.

First-Line Treatment Algorithm

For Mild to Moderate Headache:

Start with NSAIDs plus antiemetic 1:

• Naproxen sodium 500-825 mg OR ibuprofen 400-800 mg OR aspirin 1000 mg 1
• Add metoclopramide 10 mg 20-30 minutes before the NSAID for synergistic analgesia and to treat nausea 1, 2
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic effects 2, 3

For Moderate to Severe Headache:

Use combination triptan + NSAID + antiemetic 1:

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is the most evidence-based combination, with 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 1, 2
• Add metoclopramide 10 mg or prochlorperazine 10 mg for nausea 1, 2
• This combination is superior to monotherapy and represents the strongest recommendation from current guidelines 1, 2

Route Selection Based on Severity of Nausea/Vomiting

When Significant Vomiting is Present:

Use non-oral routes to bypass the gastrointestinal tract 1, 3:

• Subcutaneous sumatriptan 6 mg provides the highest efficacy with onset within 15 minutes and 59% complete pain relief by 2 hours 1, 2
• Intranasal sumatriptan 5-20 mg is an alternative non-oral option 2
• IV metoclopramide 10 mg for antiemetic and analgesic effects 2
• IV ketorolac 30 mg for rapid pain relief with approximately 6 hours duration 2

When Nausea Without Vomiting is Present:

Oral medications can be used, but add antiemetic 3:

• Nausea itself warrants antiemetic treatment as it is one of the most disabling symptoms, not just the vomiting 3
• Oral triptan + NSAID combination with oral metoclopramide 10 mg or prochlorperazine 25 mg 1, 2

Critical Medication Frequency Limitation

Limit all acute migraine medications to no more than 2 days per week (10 days per month for triptans, 15 days per month for NSAIDs) to prevent medication-overuse headache 1, 2:

• Medication-overuse headache develops when acute medications are used ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1, 2
• This creates a vicious cycle of increasing headache frequency and potentially daily headaches 1
• If the patient requires acute treatment more than twice weekly, initiate preventive therapy immediately 1, 2

Antiemetic Selection and Considerations

Metoclopramide vs. Prochlorperazine:

Both are effective prokinetic antiemetics 1:

• Metoclopramide 10 mg IV/oral provides direct analgesic effects beyond antiemetic properties 2
• Prochlorperazine 10 mg IV or 25 mg oral has comparable efficacy with a more favorable side effect profile than chlorpromazine (21% vs 50% adverse events) 2
• Both can cause akathisia, which can be treated with diphenhydramine if it develops 4
• Metoclopramide is contraindicated in pheochromocytoma, seizure disorder, GI bleeding, and GI obstruction 2
• Prochlorperazine has additional risks of tardive dyskinesia, hypotension, and arrhythmias 2

Alternative Antiemetic:

• Ondansetron is as effective as promethazine and not associated with sedation or akathisia, making it suitable as first-line for nausea when dopamine antagonists are contraindicated 4

When First-Line Treatment Fails

If One Triptan Fails:

Try a different triptan, as failure of one does not predict failure of others 1, 2:

• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes (fastest oral triptan) 2
• Eletriptan 40 mg or zolmitriptan 2.5-5 mg are reportedly more effective with fewer adverse reactions than sumatriptan 2
• Naratriptan has the longest half-life, which may decrease recurrent headaches 2
• Try each triptan for 2-3 headache episodes before abandoning it 2

If All Triptans Fail:

Escalate to third-line agents 1:

• Gepants (ubrogepant 50-100 mg or rimegepant) have no vasoconstriction, making them safe for patients with cardiovascular contraindications 1, 2
• Lasmiditan 50-200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, but patients cannot drive for at least 8 hours after intake 1, 2
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy 1, 2

Medications to Absolutely Avoid

Never use opioids or butalbital-containing compounds for acute migraine treatment 1:

• These have questionable efficacy and are associated with considerable adverse effects including dependency, rebound headaches, and eventual loss of efficacy 1, 2
• The 2025 American College of Physicians guideline explicitly states "Do not use opioids or butalbital for the treatment of acute episodic migraine" 1

Avoid oral ergot alkaloids (ergotamine) 1:

• These are poorly effective and potentially toxic, with risks including myocardial infarction, fibrosis, and vasospastic ischemia 1, 2
• Should not be used as a substitute for triptans 1

When to Initiate Preventive Therapy

Start preventive therapy if the patient experiences 1, 2:

• Two or more attacks per month producing disability lasting 3+ days 2
• Use of acute medication more than 2 days per week 1, 2
• Inadequate response to optimized acute therapy 1
• Contraindication to acute treatments 2

Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments, with efficacy requiring 2-3 months for oral agents to assess 1, 2.

Common Pitfalls to Avoid

• Do not restrict antiemetics only to patients who are vomiting—nausea itself is highly disabling and warrants treatment 3
• Do not delay treatment—advise early use of acute medications while headache is still mild for maximum effectiveness 1
• Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates medication-overuse headache; instead transition to preventive therapy 2
• Do not abandon triptan therapy after a single failed attempt—try different triptans or routes of administration before escalating 2
• Do not use triptans and ergot alkaloids within 24 hours of each other due to additive vasoconstrictive effects 2