What is the recommended evaluation and management for an adult presenting with a new headache, including red‑flag assessment and pharmacologic treatment options?

Evaluation and Management of New Headache in Adults

For an adult presenting with a new headache, first exclude secondary causes by screening for red-flag features, then initiate evidence-based acute treatment with NSAIDs or combination therapy for mild-to-moderate pain, escalating to triptans for moderate-to-severe attacks, while strictly limiting acute medication use to ≤2 days per week to prevent medication-overuse headache. 1

Red-Flag Assessment (Mandatory First Step)

Before diagnosing primary headache, systematically evaluate for features suggesting urgent secondary causes that require immediate neuroimaging: 2, 3, 4

• Thunderclap onset (sudden, severe, "worst headache of life") 2, 3, 4
• New headache after age 50 2, 3, 4
• Progressive worsening or increased frequency/severity 2, 4
• Focal neurological deficits (weakness, sensory loss, visual field cuts) 2, 3
• Altered consciousness or impaired memory 2, 3
• Papilledema on fundoscopic examination 2, 3
• Fever with neck stiffness (meningismus) 2, 4
• Recent head trauma 2, 3, 4
• Headache provoked by Valsalva, cough, exertion, or postural changes 3
• Underlying cancer or immunosuppression 5, 3
• Pregnancy or anticoagulant therapy 3, 4

Imaging Recommendations When Red Flags Present

• MRI brain with and without contrast is the preferred modality for detailed evaluation and posterior fossa imaging 2, 3
• Non-contrast CT followed by lumbar puncture if CT is normal when subarachnoid hemorrhage is suspected 2
• No imaging is required for typical primary headache patterns without red-flag features 2, 3

Acute Pharmacologic Treatment Algorithm

First-Line: Mild-to-Moderate Headache

Start with NSAIDs or combination analgesics as initial therapy: 1, 5

• Naproxen sodium 500–825 mg at headache onset 1
• Ibuprofen 400–800 mg 1
• Aspirin 1000 mg 1
• Acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg (combination therapy achieves pain reduction in 59.3% at 2 hours) 6

Critical timing: Treat early when pain is still mild—this achieves pain-free response in ≈50% versus only ≈28% when delayed until moderate-to-severe pain 6

Second-Line: Moderate-to-Severe Headache or NSAID Failure

Escalate to triptan monotherapy or triptan + NSAID combination: 1, 5

• Sumatriptan 50–100 mg PLUS naproxen 500 mg (strongest recommendation; superior to either agent alone with NNT 3.5 for 2-hour relief) 1, 6
• Rizatriptan 10 mg (fastest oral triptan, peak at 60–90 minutes) 1
• Eletriptan 40 mg or zolmitriptan 2.5–5 mg 1
• Subcutaneous sumatriptan 6 mg (highest efficacy: 59% pain-free at 2 hours, onset within 15 minutes; reserve for severe attacks or significant nausea/vomiting) 1, 6

Triptan contraindications: Ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, basilar or hemiplegic migraine 6, 5

Third-Line: When Triptans Fail or Are Contraindicated

Consider newer CGRP antagonists (gepants) or ditans: 1, 5

• Ubrogepant 50–100 mg or rimegepant (no vasoconstriction; safe in cardiovascular disease) 1, 5
• Lasmiditan 50–200 mg (5-HT1F agonist; safe in cardiovascular risk but requires 8-hour driving restriction due to CNS effects) 5
• Zavegepant intranasal 1

Adjunctive Antiemetic Therapy

Add antiemetics 20–30 minutes before analgesics for synergistic benefit: 1, 6

• Metoclopramide 10 mg IV/oral (provides direct analgesic effect beyond antiemetic properties) 1, 6
• Prochlorperazine 10 mg IV or 25 mg rectal (comparable efficacy to metoclopramide with fewer adverse events than chlorpromazine) 1, 6

Metoclopramide/prochlorperazine contraindications: Pheochromocytoma, seizure disorder, GI obstruction, CNS depression 6

Parenteral Options for Severe Attacks or Refractory Cases

Reserve for emergency/urgent care settings: 1, 6

• Ketorolac 30 mg IV (rapid onset, 6-hour duration, minimal rebound risk) 1, 6
• Metoclopramide 10 mg IV + ketorolac 30 mg IV (first-line IV combination) 6
• Dihydroergotamine (DHE) 0.5–1.0 mg IV or intranasal (good evidence as monotherapy when NSAIDs contraindicated) 1, 6

DHE contraindications: Concurrent triptan use within 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, sepsis 6

Critical Medication-Overuse Headache Prevention

Strictly limit ALL acute headache medications to ≤2 days per week (≤10 days per month): 1, 6

• Frequent use (>2 days/week) paradoxically increases headache frequency and can lead to daily chronic headaches 1
• Triptans trigger medication-overuse headache at ≥10 days/month; NSAIDs at ≥15 days/month 1
• If acute treatment is needed >2 days/week, immediately initiate preventive therapy 1

Absolutely Contraindicated Therapies

Never prescribe opioids or butalbital-containing compounds for headache: 1, 6, 5

• Opioids (codeine, hydromorphone, morphine, tramadol) provide questionable efficacy, cause dependency, precipitate rebound headaches, and worsen long-term outcomes 1, 6
• Reserve opioids only when every other evidence-based treatment is contraindicated, sedation is acceptable, and abuse risk has been formally assessed 1
• Butorphanol nasal spray has better evidence than oral opioids if an opioid must be used 6

Indications for Preventive Therapy

Initiate preventive treatment when: 1, 6

• ≥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
• Patient preference for prevention over acute treatment 1

First-Line Preventive Medications

• Propranolol 80–240 mg/day or timolol 20–30 mg/day (beta-blockers without intrinsic sympathomimetic activity; strong RCT evidence) 1, 7
• Topiramate 50–100 mg/day (only oral preventive with proven efficacy in chronic migraine) 1
• Amitriptyline 10–100 mg at night (preferred for comorbid depression/anxiety or mixed migraine-tension headache) 1

Third-Line Preventive Options

• OnabotulinumtoxinA 155–195 units every 12 weeks (only FDA-approved therapy for chronic migraine; requires specialist administration) 1
• CGRP monoclonal antibodies: erenumab 70–140 mg monthly, fremanezumab 225 mg monthly or 675 mg quarterly 1

Follow-Up and Monitoring

Implement systematic tracking and reassessment: 1

• Headache diary (paper or smartphone) to record frequency, severity, triggers, and medication use 1
• Evaluate treatment response 2–3 months after initiation or change 1
• Regular reassessment every 6–12 months to adjust management 1
• Refer to headache specialist when diagnosis is uncertain, all treatments fail, or complications arise 1

Common Pitfalls to Avoid

• Do not allow patients to increase acute medication frequency in response to treatment failure—this creates medication-overuse headache; instead transition to preventive therapy 1, 6
• Do not abandon triptan therapy after a single failed attempt—failure of one triptan does not predict failure of others; try at least 2–3 different triptans before escalating 6
• Do not delay preventive therapy while trialing multiple acute strategies when headaches occur >2 days/week 1
• Do not order neuroimaging for typical recurrent headache without red-flag features—this increases cost, radiation exposure, and risk of incidental findings 2, 3