What is the recommended treatment for a patient with recurrent headaches?

Treatment of Recurrent Headaches

For recurrent 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 for mild to moderate attacks, while strictly limiting acute medication use to no more than 2 days per week to prevent medication-overuse headache. 1

Initial Assessment and Diagnosis

Before initiating treatment, determine the headache type through systematic history-taking:

• Frequency and timing: Document how many headache days per month occur, as ≥15 days per month for >3 months suggests chronic migraine 1
• Pain characteristics: Suspect migraine if pain is unilateral, pulsating, moderate to severe intensity, and worsened by physical activity 1
• Associated symptoms: Presence of photophobia, phonophobia, nausea, and/or vomiting strongly supports migraine diagnosis 1
• Aura symptoms: Visual, sensory, or speech disturbances lasting 5-60 minutes and spreading gradually over ≥5 minutes indicate migraine with aura 1
• Medication history: Critical to assess current use of all acute medications, including over-the-counter analgesics, to identify medication-overuse headache 1

Red flags requiring urgent evaluation and neuroimaging include: headache with fever and neck stiffness, thunderclap onset, progressive worsening, new onset after age 50, abnormal neurologic examination, or headache awakening patient from sleep 1

Acute Treatment Algorithm

For Mild to Moderate Attacks

First-line therapy: NSAIDs as monotherapy 1

• Naproxen sodium 500-825 mg at onset 1
• Ibuprofen 400-800 mg at onset 1
• Aspirin 1000 mg at onset 1
• Combination products containing acetaminophen, aspirin, and caffeine 1

Critical timing: Begin treatment as soon as possible after headache onset, ideally when pain is still mild, to improve efficacy 1

For Moderate to Severe Attacks

First-line therapy: Combination of triptan plus NSAID 1

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 2
• This combination represents the strongest recommendation from the 2025 American College of Physicians guidelines with high-certainty evidence 1

Alternative triptan options if sumatriptan is ineffective or not tolerated 1:

• Rizatriptan
• Naratriptan
• Zolmitriptan
• Eletriptan (40-80 mg achieves 54-77% headache response at 2 hours) 3

For severe nausea/vomiting: Use nonoral triptan formulations 1

• Subcutaneous sumatriptan 6 mg (most rapid and effective route, 59% pain-free at 2 hours) 4
• Intranasal sumatriptan 5-20 mg 2
• Intranasal zolmitriptan 1

Adjunctive Antiemetic Therapy

Add antiemetic for nausea/vomiting 1:

• Metoclopramide 10 mg (provides independent analgesic benefit beyond antiemetic effect) 1, 2
• Prochlorperazine 10 mg (comparable efficacy to metoclopramide) 2

Critical Frequency Limitation

Limit ALL acute medications to no more than 2 days per week to prevent medication-overuse headache 1, 5

Specific thresholds for medication-overuse headache 1:

• NSAIDs: ≥15 days per month for ≥3 months 5
• Triptans: ≥10 days per month for ≥3 months 5
• Any combination of acute medications: ≥10 days per month for ≥3 months 1

Medications to Avoid

Never use for migraine treatment 1:

• Opioids (cause dependency, rebound headaches, and loss of efficacy) 1
• Butalbital-containing compounds (highest risk of medication-overuse headache) 1, 5

When to Initiate Preventive Therapy

Preventive therapy is indicated when 1:

• Headaches occur ≥2 times per week 1
• Two or more attacks per month produce disability lasting ≥3 days 1
• Acute medications are used more than twice weekly 1
• Acute treatments fail or are contraindicated 1
• Patient has ≥15 headache days per month (chronic migraine) 1

First-line preventive options 5:

• Topiramate (proven beneficial for chronic migraine) 5
• OnabotulinumtoxinA (for chronic migraine using Phase III protocol) 5
• Amitriptyline (second choice, effective but causes sedation and weight gain) 5

Management of Medication-Overuse Headache

If medication-overuse headache is suspected (≥15 headache days per month with regular overuse of acute medications for >3 months) 1:

Immediate withdrawal protocol 5:

• Complete, immediate cessation of all overused medications 5
• Start preventive therapy simultaneously, as continuing offending agents prevents any preventive treatment from working 5
• Provide preemptive education on medication overuse headache risk at every visit 5

Exception: Patients overusing opioids, barbiturates, or benzodiazepines require slow tapering and possibly inpatient treatment to prevent acute withdrawal 6

Newer Treatment Options (When First-Line Fails)

CGRP antagonists (gepants) 1:

• Rimegepant or ubrogepant
• May have lower likelihood of pain freedom than triptan plus NSAID combination (low-certainty evidence) 1
• Significantly more expensive (annualized cost $4,959-$5,994) 1
• Consider only when triptans are contraindicated or ineffective after adequate trials 2

Lasmiditan (5-HT1F agonist) 1:

• Insufficient comparative effectiveness evidence for prioritized outcomes 1
• May be safe in patients with cardiovascular risk factors where triptans are contraindicated 7

Lifestyle Modifications

Essential non-pharmacologic interventions 1:

• Maintain adequate hydration 1
• Regular meals without skipping 1
• Consistent sleep schedule with sufficient duration 1
• Regular moderate to intense aerobic exercise 1
• Stress management with relaxation techniques or mindfulness 1
• Weight loss for patients who are overweight or obese 1
• Identify and avoid individual migraine triggers through detailed history 1

Common Pitfalls to Avoid

• Do not allow escalating acute medication use when treatment fails; instead transition to preventive therapy 2
• Do not prescribe daily analgesics, as this worsens rather than helps the problem 5
• Do not assume failure of one triptan predicts failure of others; try different triptans before escalating to third-line agents 2
• Do not delay treatment; early administration during mild pain phase improves efficacy 1, 4
• Maintain headache diary to track headache days and medication use, facilitating early detection of overuse patterns 5