What medications are appropriate for treating headaches?

Medications for Headaches

For acute migraine treatment, start with NSAIDs (ibuprofen 400–800 mg, naproxen 500–825 mg, or aspirin 1000 mg) for mild-to-moderate attacks, and add a triptan (sumatriptan 50–100 mg or rizatriptan 10 mg) to the NSAID for moderate-to-severe attacks or when NSAIDs fail—this combination is superior to either agent alone. 1

First-Line Acute Treatment Algorithm

Mild-to-Moderate Headache

• NSAIDs are the initial choice: ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg taken at headache onset 1
• Acetaminophen 1000 mg is an alternative when NSAIDs are contraindicated, though less effective 1, 2
• Combination therapy (aspirin 500–1000 mg + acetaminophen 1000 mg + caffeine 130 mg) provides synergistic analgesia and is highly effective for mild-to-moderate attacks 1, 2

Moderate-to-Severe Headache or NSAID Failure

• Add a triptan to your NSAID regimen rather than switching—the combination of sumatriptan 50–100 mg + naproxen 500 mg produces 130 additional patients per 1000 achieving sustained pain relief at 48 hours compared to either drug alone 1
• Oral triptans with strong evidence: sumatriptan 50–100 mg, rizatriptan 10 mg, eletriptan 40 mg, zolmitriptan 2.5–5 mg, naratriptan 1, 3
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes—reserve for severe attacks with rapid progression or significant vomiting 1, 2
• Intranasal formulations (sumatriptan 5–20 mg or zolmitriptan nasal spray) are useful when nausea prevents oral intake 1, 2

Timing Is Critical

• Treat early when pain is still mild: approximately 50% of patients become pain-free at 2 hours versus only 28% when treatment is delayed until pain is moderate-to-severe 1

Tension-Type Headache Treatment

• Ibuprofen 400 mg or acetaminophen 1000 mg for acute episodes 1
• Amitriptyline 30–150 mg/day for prevention of chronic tension-type headache 1

Emergency Department / Parenteral Options

First-Line IV Combination

• Metoclopramide 10 mg IV + ketorolac 30 mg IV provides rapid relief with minimal rebound risk 2
• Prochlorperazine 10 mg IV is equally effective to metoclopramide and must be offered to eligible patients (Level A recommendation) 4

Alternative Parenteral Agents

• Dexketoprofen IV or ketorolac IV (Level B—should offer) 4
• Subcutaneous sumatriptan 6 mg (Level B—should offer) 4
• Dihydroergotamine 0.5–1.0 mg IV or intranasal has good evidence as monotherapy 1
• Greater occipital nerve block must be offered (Level A recommendation) 4

Third-Line Options (After Triptan-NSAID Failure)

• CGRP antagonists (gepants): ubrogepant 50–100 mg or rimegepant—reserve for patients who fail combination therapy or have cardiovascular contraindications to triptans 1, 5
• Lasmiditan 50–200 mg (5-HT₁F agonist) is safe in patients with cardiovascular disease but requires an 8-hour no-driving restriction 1, 6

Critical Medication-Overuse Prevention

Limit ALL acute headache medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2

• This limit applies to NSAIDs, triptans, acetaminophen, gepants, combination analgesics, and antiemetics 1
• If you need acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing acute medication frequency 1

Preventive Therapy Indications

Start preventive therapy when patients have:

• ≥2 migraine attacks per month causing disability lasting ≥3 days 1
• Acute medication use >2 days per week 1
• Contraindication to or failure of acute therapies 1

First-Line Preventive Medications

• Beta-blockers: propranolol 80–240 mg/day or timolol 20–30 mg/day 1
• Topiramate or valproate (avoid valproate in women of childbearing potential due to teratogenic risk) 1
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) for episodic migraine 1
• OnabotulinumtoxinA (Botox) for chronic migraine (≥15 headache days/month) but NOT for episodic migraine 1

Second-Line Preventive Options

• Amitriptyline 30–150 mg/day especially when comorbid depression, anxiety, or mixed migraine/tension-type headache exists 1
• Lisinopril, candesartan, magnesium, memantine 1

Absolutely Contraindicated Medications

Never prescribe opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) or butalbital-containing compounds for migraine—they have questionable efficacy, high dependence risk, cause rebound headaches, and worsen long-term outcomes. 1, 2, 3

• Hydromorphone IV must not be offered in the emergency department (Level A recommendation) 4
• Butorphanol nasal spray has better evidence than other opioids but remains a last-resort option only when all other therapies are contraindicated 1, 3

Triptan Contraindications

Avoid triptans in patients with:

• Ischemic heart disease, previous myocardial infarction, or coronary artery vasospasm 2
• Uncontrolled hypertension (systolic ≥160 or diastolic ≥100) 2
• Cerebrovascular disease, history of stroke or TIA 2
• Basilar or hemiplegic migraine 2

Common Pitfalls to Avoid

• Do not abandon triptan therapy after one failed attempt—if one triptan is ineffective after 2–3 episodes, try a different triptan, as failure of one does not predict failure of others 2, 3
• Do not substitute opioids as "rescue" medication when triptans fail—escalate to gepants, lasmiditan, or parenteral therapies instead 1, 2
• Do not delay preventive therapy in patients requiring acute treatment more than twice weekly—this perpetuates the cycle of frequent attacks 1
• Do not use gabapentin for migraine prevention—it is not recommended for episodic migraine 1

Special Populations

Pregnancy

• Acetaminophen is the safest option 6
• Avoid NSAIDs in the third trimester 6
• Triptans have limited safety data; discuss risks versus benefits 6
• Absolutely avoid valproate due to teratogenic risk 1

Hypertension

• Acetaminophen 1000 mg is safest when hypertension is uncontrolled 2
• NSAIDs can elevate blood pressure and are relatively contraindicated in uncontrolled hypertension 2
• Treating the headache often improves blood pressure without requiring antihypertensive medication 7