What are the recommended treatments for headaches?

Headache Treatment

For acute migraine headaches, start with combination therapy of a triptan plus an NSAID (such as sumatriptan 50-100 mg with naproxen 500 mg) for moderate to severe attacks, or NSAIDs alone (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) for mild to moderate attacks. 1

First-Line Treatment Algorithm

Mild to Moderate Migraine

• Begin with NSAIDs as monotherapy: ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg 1
• Acetaminophen 1000 mg is an alternative if NSAIDs are contraindicated, though it has inferior efficacy (NNT of 12 for 2-hour pain-free response versus NNT of 7.2 for ibuprofen 400 mg) 1, 2, 3
• Add metoclopramide 10 mg orally 15-20 minutes before the analgesic to enhance absorption and provide synergistic analgesia, even without vomiting 1, 4

Moderate to Severe Migraine

• Use combination therapy with a triptan plus NSAID from the start: sumatriptan 50-100 mg plus naproxen 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 1, 4
• This combination is superior to monotherapy with either drug and represents the strongest evidence-based recommendation 1
• Take medication as early as possible when pain is still mild to maximize effectiveness 1, 4

Severe Migraine with Nausea/Vomiting

• Switch to non-oral routes: subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes 1, 4, 5
• Alternative: intranasal sumatriptan 5-20 mg or intranasal zolmitriptan 10 mg 1, 4
• Add an antiemetic: metoclopramide 10 mg IV or prochlorperazine 10 mg IV 1, 4

Second-Line Options for Treatment Failure

When First-Line Therapy Fails

• Try a different triptan before abandoning the class entirely, as failure of one triptan does not predict failure of others 4
• Consider CGRP antagonists (gepants): rimegepant, ubrogepant, or zavegepant for patients who do not tolerate or have inadequate response to triptan plus NSAID combination 1
• Lasmiditan (ditan) is reserved for patients who fail all other treatments in this guideline 1

Intravenous "Headache Cocktail" for Emergency Settings

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV is the most effective combination for severe migraine in urgent care settings 4
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy but potentially more favorable side effect profile (21% adverse events versus 50% with chlorpromazine) 4
• Dihydroergotamine (DHE) IV or intranasal is an alternative with good evidence for efficacy 1, 4

Tension-Type Headache Treatment

• Ibuprofen 400 mg or acetaminophen 1000 mg for acute tension-type headache 1, 6
• For chronic tension-type headache prevention, use amitriptyline 30-150 mg/day 1, 6
• Botulinum toxin injection is NOT recommended for chronic tension-type headache prevention 1

Cluster Headache Treatment

Acute Treatment

• Subcutaneous sumatriptan 6 mg or intranasal zolmitriptan 10 mg for acute cluster headache attacks 1, 6
• Normobaric oxygen therapy is also effective for acute treatment 1

Prevention

• Galcanezumab for episodic cluster headache prevention 1, 6
• Do NOT use galcanezumab for chronic cluster headache (weak recommendation against) 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit ALL acute migraine medications to no more than 2 days per week to prevent medication-overuse headache, which occurs at ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1, 4

• If patients require acute treatment more than twice weekly, initiate preventive therapy immediately 1, 4
• Medication-overuse headache leads to increasing headache frequency and potentially daily headaches, creating a vicious cycle 1, 4

Medications to AVOID

• Do NOT use opioids (including hydromorphone) for acute migraine treatment—they lead to dependency, rebound headaches, and loss of efficacy 1, 4
• Do NOT use butalbital-containing compounds for acute episodic migraine 1
• Reserve opioids only for cases where all other medications are contraindicated, sedation is not a concern, and abuse risk has been addressed 4

When to Initiate Preventive Therapy

Preventive therapy is indicated when: 1, 4

• Two or more attacks per month producing disability lasting 3+ days
• Using acute medications more than 2 days per week
• Contraindication to or failure of acute treatments
• Presence of uncommon migraine conditions (hemiplegic migraine, basilar migraine, prolonged aura, migrainous infarction)

First-line preventive options include propranolol 80-240 mg/day, topiramate, amitriptyline 30-150 mg/day, or CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) 1, 4, 6

Special Populations

Pregnancy and Breastfeeding

• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation before initiating therapy 1
• Valproate is strictly contraindicated due to teratogenic risk 4
• Acetaminophen and certain NSAIDs may be safer options, but individualized risk-benefit discussion is essential 1

Cardiovascular Contraindications

• Triptans are contraindicated in patients with ischemic heart disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 4, 7
• In these patients, use NSAIDs, acetaminophen, or CGRP antagonists as alternatives 1, 4

Cost Considerations

• Prescribe less costly recommended medications when equally effective 1
• Generic NSAIDs and triptans are significantly less expensive than newer CGRP antagonists (annualized cost $4,959-$8,800 for gepants versus generic options) 1
• Over-the-counter medications (acetaminophen, ibuprofen, naproxen, aspirin) are cost-effective first-line options for mild-to-moderate attacks 8