In a healthy 22‑year‑old with persistent headaches not relieved by a full therapeutic dose of ibuprofen (800 mg), what is the appropriate next step in evaluation and management?

Evaluation and Management of Persistent Headaches in a 22-Year-Old

In a healthy 22-year-old with headaches not responding to ibuprofen 800 mg, the most appropriate next step is to establish whether this represents migraine (the most likely diagnosis in this age group) and escalate to triptan therapy if the headache is moderate-to-severe, while ensuring acute medication use remains limited to ≤2 days per week to prevent medication-overuse headache. 1

Immediate Diagnostic Assessment

Confirm Migraine Diagnosis

• Suspect migraine without aura if the patient experiences recurrent moderate-to-severe headaches that are unilateral and/or pulsating, accompanied by photophobia, phonophobia, nausea, and/or vomiting, with attacks lasting 4–72 hours when untreated. 1
• A positive family history of migraine and symptom onset around puberty strengthen the diagnosis. 1
• The medical history should capture: age at onset, attack duration, attack frequency, pain characteristics (location, quality, severity), accompanying symptoms, and any aura symptoms. 1

Rule Out Red Flags Requiring Urgent Imaging

• Neuroimaging (MRI preferred) is indicated only when red-flag features are present, including thunderclap onset, progressive worsening, fever with neck stiffness, focal neurological deficits, impaired memory or consciousness, headache aggravated by Valsalva maneuvers, or new-onset headache after age 50. 1
• In a healthy 22-year-old with typical recurrent headache and normal neurologic examination, neuroimaging is not warranted. 1

Escalation of Acute Treatment

Why Ibuprofen 800 mg May Have Failed

• Ibuprofen 400–800 mg is effective first-line therapy for mild-to-moderate migraine, achieving headache relief in approximately 57% of patients at 2 hours (versus 25% with placebo), with a number-needed-to-treat of 3.2. 2, 3
• However, in patients with severe baseline pain intensity, ibuprofen may be insufficient, and triptans are required. 2
• Delayed administration (waiting until pain is severe) reduces efficacy; NSAIDs work best when taken early while pain is still mild. 4

Immediate Next Step: Add or Switch to Triptan Therapy

• For moderate-to-severe migraine or when NSAIDs fail after 2–3 episodes, escalate to triptan therapy. 1, 4
• First-line triptan options include sumatriptan 50–100 mg, rizatriptan 10 mg, eletriptan 40 mg, or zolmitriptan 2.5–5 mg. 1, 4
• Combination therapy (triptan + NSAID) is superior to either agent alone, providing sustained pain relief in 130 additional patients per 1,000 compared with triptan monotherapy. 4
• Specifically, sumatriptan 50–100 mg plus naproxen 500 mg is the strongest-rated intervention for moderate-to-severe migraine, with a number-needed-to-treat of 3.5 for headache relief at 2 hours. 4

Alternative Acute Options if Triptans Are Contraindicated

• Gepants (ubrogepant 50–100 mg or rimegepant) are third-line oral alternatives when triptans are contraindicated due to cardiovascular disease or uncontrolled hypertension. 4
• Lasmiditan (Reyvow) 50–200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, but patients must not drive or operate machinery for at least 8 hours after use. 4
• Intranasal or intravenous dihydroergotamine (DHE) has good evidence for efficacy as monotherapy. 1, 4

Critical Medication-Overuse Prevention

Strict Frequency Limits

• All acute migraine medications—including NSAIDs, triptans, gepants, and combination analgesics—must be limited 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, 4
• If the patient requires acute treatment more than twice weekly, preventive therapy must be initiated immediately. 1, 4

Medications to Absolutely Avoid

• Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) are absolutely contraindicated for migraine treatment because they provide questionable efficacy, carry high risk of dependence, precipitate rebound headaches, and worsen overall migraine outcomes. 1, 4
• Butalbital-containing compounds should be avoided due to high risk of medication-overuse headache and dependency. 1, 4

Indications for Preventive Therapy

When to Initiate Prevention

• Preventive therapy is indicated if the patient experiences ≥2 migraine attacks per month causing disability lasting ≥3 days, uses acute medication >2 days per week, has contraindications to or failure of acute treatments, or has uncommon migraine subtypes. 1, 4
• First-line preventive medications include beta-blockers without intrinsic sympathomimetic activity (propranolol 80–240 mg/day, timolol 20–30 mg/day), topiramate 50–100 mg daily, or candesartan. 1, 4
• Amitriptyline 30–150 mg at night is preferred when patients have comorbid depression, anxiety, sleep disturbances, or mixed migraine plus tension-type headache. 1, 4
• Efficacy of oral preventives requires 2–3 months of treatment before assessment. 1

Practical Management Algorithm

1. Confirm migraine diagnosis through systematic history (attack characteristics, associated symptoms, family history). 1
2. Rule out red flags; if present, obtain MRI brain with and without contrast. 1
3. If ibuprofen 800 mg has failed after 2–3 episodes, escalate to sumatriptan 50–100 mg plus naproxen 500 mg for the next attack. 4
4. Instruct the patient to take medication early (when pain is still mild) for maximum effectiveness. 4
5. Strictly limit acute medication use to ≤2 days per week; if this threshold is exceeded, initiate preventive therapy. 1, 4
6. Provide a headache diary to track attack frequency, severity, triggers, and medication use. 1
7. Schedule follow-up in 2–3 months to assess treatment response and adjust therapy as needed. 1

Common Pitfalls to Avoid

• Do not continue escalating acute medication frequency in response to treatment failure; this creates a vicious cycle of medication-overuse headache. 4
• Do not prescribe opioids simply because the patient reports "nothing else has worked" without ensuring adequate trials of NSAIDs, triptans, and combination therapy. 4
• Do not delay preventive therapy while trialing multiple acute strategies; this undermines timely control of migraine. 4
• Failure of one triptan does not predict failure of others; if sumatriptan is ineffective, try rizatriptan, eletriptan, or zolmitriptan before abandoning triptan therapy. 4