What is the best approach to diagnose and manage new headaches in a patient without red flag symptoms?

Management of New Headaches Without Red Flags

For new headaches without red flag symptoms, begin with a detailed headache-specific history focusing on frequency, timing, character, location, duration, associated symptoms, and triggers to differentiate primary headache types, followed by a targeted physical and neurologic examination—neuroimaging is not routinely indicated in patients with normal neurologic examinations and typical primary headache features. 1

Initial Diagnostic Approach

Critical History Elements to Obtain

• Frequency and timing: When headaches occur, time of day, relationship to menstrual cycle in women 1
• Pain characteristics: Location (unilateral vs bilateral, frontal vs occipital), quality (throbbing vs pressing/tightening), severity, duration (hours vs days) 1
• Associated symptoms: Nausea/vomiting, photophobia, phonophobia, visual changes, autonomic symptoms (lacrimation, rhinorrhea, ptosis) 1
• Aggravating factors: Physical activity, Valsalva maneuver, position changes, specific triggers (foods, stress, sleep patterns, odors) 1
• Medication history: Current over-the-counter or prescribed medications, their effectiveness, frequency of use (critical for identifying medication overuse) 1
• Red flag screening: New onset after age 50, progressive worsening, awakening from sleep, trauma history, systemic symptoms, neurologic symptoms 1, 2, 3

Physical and Neurologic Examination

• Complete neurologic examination is mandatory to identify focal deficits, papilledema, neck stiffness, or other concerning findings 1, 3
• Normal neurologic examination substantially reduces the likelihood of secondary pathology and need for neuroimaging 1, 4

When Neuroimaging is NOT Indicated

Neuroimaging is not warranted in patients with normal neurologic examinations and headache patterns consistent with primary headache disorders (migraine, tension-type, cluster). 1

• The yield of neuroimaging in patients with headache and normal neurologic examination is extremely low: brain tumors 0.8%, arteriovenous malformations 0.2%, aneurysms 0.1% 4
• In migraine specifically, neuroimaging yields even lower rates: brain tumors 0.3%, arteriovenous malformations 0.07%, aneurysms 0.07% 4

When Neuroimaging IS Indicated

Consider neuroimaging (MRI preferred) when any of the following are present: 1, 2, 3

• Unexplained abnormal findings on neurologic examination 1
• Rapidly increasing headache frequency 1
• History of uncoordination or focal neurologic signs/symptoms 1
• Headache awakening patient from sleep 1, 2
• Abrupt onset of severe headache ("thunderclap") 1, 2
• Marked change in established headache pattern 1
• Persistent headache following head trauma 1, 2
• New onset in patients over age 50 2, 4
• Headache worsened by Valsalva maneuver 1
• Atypical features not meeting strict migraine criteria 1

Common pitfall: Isolated occipital location, especially in children, warrants diagnostic caution as this is not characteristic of primary headache disorders 5

Differentiating Primary Headache Types

Migraine Features 1

• Duration: 4-72 hours when untreated 1
• Pain characteristics: At least 2 of the following: unilateral location, pulsating quality, moderate-to-severe intensity, aggravation by routine physical activity 1
• Associated symptoms: At least 1 of the following: nausea/vomiting, photophobia and phonophobia 1
• Requires: At least 5 lifetime attacks meeting these criteria 1

Tension-Type Headache Features 1

• Pain characteristics: Bilateral location, pressing/tightening (non-pulsating) quality, mild-to-moderate intensity 1
• Not aggravated by routine physical activity 1
• Absence of nausea/vomiting (though may have anorexia) 1
• Absence of both photophobia and phonophobia (may have one or the other) 1

Cluster Headache Features 1

• Severe unilateral orbital, supraorbital, or temporal pain 1
• Autonomic symptoms: Ipsilateral lacrimation, conjunctival injection, nasal congestion, rhinorrhea, forehead/facial sweating, ptosis, miosis, eyelid edema 1
• Restlessness or agitation during attacks 1

Acute Treatment Algorithm

First-Line: NSAIDs 1

• Acetylsalicylic acid (aspirin), ibuprofen, or diclofenac potassium have the strongest evidence for acute migraine treatment 1
• Administer as early as possible during an attack for optimal efficacy 1
• Paracetamol (acetaminophen) has less efficacy; reserve for NSAID-intolerant patients 1

Second-Line: Triptans 1, 6

• Offer triptans when over-the-counter analgesics provide inadequate relief 1
• Most effective when taken early in attack while headache is still mild 1
• Do not use during aura phase 1
• Sumatriptan dosing: 50 mg or 100 mg orally provides superior response compared to 25 mg; no additional benefit above 50 mg 6
• Headache response (reduction to mild or no pain) achieved in 50-62% at 2 hours and 65-79% at 4 hours with sumatriptan 50-100 mg vs 17-27% with placebo 6
• If one triptan fails, others may still provide relief 1
• For rapid peak intensity or vomiting, consider subcutaneous sumatriptan 1

Managing Relapses 1

• Upon relapse (return of symptoms within 48 hours), patients may repeat triptan treatment or combine with fast-acting naproxen sodium, ibuprofen lysine, or diclofenac potassium 1
• Critical warning: Repeating treatment does not prevent further relapses and increases medication overuse headache risk 1

Third-Line: Ditans or Gepants 1

• Consider lasmiditan (ditan) or ubrogepant/rimegepant (gepants) if all triptans fail after adequate trial (no/insufficient response in at least 3 consecutive attacks) or are contraindicated 1
• Lasmiditan efficacy comparable to triptans but causes temporary driving impairment 1

Preventive Therapy Considerations

Consider preventive medications when: 7

• More than 2 headaches per week 1
• Frequent episodic migraine or inadequate response to acute treatment (no absolute minimum number of days required) 7
• Medication overuse: triptans/ergots/combination analgesics ≥10 days/month for ≥3 months, or simple analgesics ≥15 days/month for ≥3 months 7
• Chronic migraine (≥15 headache days/month for >3 months with migraine features on ≥8 days/month) 7

First-Line Preventive Options 7

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) are first-line for chronic migraine prevention with strong evidence and favorable tolerability 7
• Reduce migraine days by 2-4.8 days per month 7
• Administered as monthly subcutaneous injections 7
• Monitor blood pressure with erenumab due to postmarketing warnings for hypertension development/worsening 7

Second-Line Preventive Options 7

• Topiramate is the only traditional preventive with randomized controlled trial evidence specifically in chronic migraine 7
• Start 25 mg daily, titrate slowly to 100-200 mg daily in divided doses 7
• Common side effects: cognitive slowing, paresthesias, weight loss, kidney stones 7
• Full benefit may take 2-3 months; do not abandon prematurely 7

Critical Pitfalls to Avoid

• Medication overuse headache: Monitor frequency of acute medication use closely; frequent use of triptans, ergotamine, opiates, and analgesics can cause rebound headaches 1
• Premature neuroimaging: Avoid unnecessary imaging in patients with normal examinations and typical primary headache features 1, 4
• Delayed preventive therapy: Do not wait for arbitrary headache frequency thresholds; focus on functional impairment and treatment response 7
• Misdiagnosing secondary causes: Always systematically exclude red flags before diagnosing primary headache disorder 2, 3
• Ignoring occipital location: Constant occipital headache is not typical of primary headaches and warrants careful evaluation for cervicogenic headache or secondary causes 5