What is the best treatment approach for a patient with a headache who has previously used aspirin (acetylsalicylic acid) and acetaminophen (paracetamol)?

Treatment Approach for Headache After Previous Use of Aspirin and Acetaminophen

For a patient with headache who has already tried aspirin and acetaminophen without adequate relief, escalate to combination therapy with an NSAID (ibuprofen 400-800 mg or naproxen 500-825 mg) plus an antiemetic (metoclopramide 10 mg), and if this fails after 2-3 episodes, advance to triptan therapy for moderate-to-severe attacks. 1

Immediate Next-Step Treatment Algorithm

First Escalation: NSAID Monotherapy

• Try ibuprofen 400-800 mg or naproxen sodium 500-825 mg at headache onset, ideally when pain is still mild, as NSAIDs are recommended as first-line treatment for mild-to-moderate migraine attacks with demonstrated efficacy and favorable tolerability. 1
• Ibuprofen can be repeated every 4-6 hours as needed, with maximum 2400 mg/day. 2
• Naproxen can be repeated every 2-6 hours as needed, with maximum 1.5 g/day. 1

Second Escalation: Add Antiemetic for Synergistic Effect

• Combine the NSAID with metoclopramide 10 mg (oral or IV) taken 20-30 minutes before the NSAID, as metoclopramide provides direct analgesic effects through central dopamine receptor antagonism and enhances absorption of co-administered medications through prokinetic effects. 1
• Alternatively, prochlorperazine 10 mg IV or 25 mg oral/suppository effectively relieves both headache pain and nausea directly. 1

Third Escalation: Triptan Therapy

• If NSAIDs fail after 2-3 headache episodes, switch to a triptan (sumatriptan 50-100 mg, rizatriptan 10 mg, or zolmitriptan 2.5-5 mg) for moderate-to-severe attacks. 1
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan. 1
• For severe attacks with significant nausea/vomiting, consider subcutaneous sumatriptan 6 mg, which provides pain relief in 70-82% of patients within 15 minutes. 1

Fourth Escalation: Combination Triptan + NSAID

• The combination of sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy. 1

Fifth Escalation: Newer CGRP Antagonists (Gepants)

• If all triptans fail after adequate trials, escalate to gepants (ubrogepant 50-100 mg or rimegepant), which have no vasoconstriction and are safe for patients with cardiovascular contraindications. 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• Strictly limit ALL acute headache medications to no more than 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
• NSAIDs trigger medication-overuse headache at ≥15 days/month, while triptans trigger it at ≥10 days/month. 1

When to Initiate Preventive Therapy

Immediately start preventive therapy if the patient:

• Requires acute treatment more than twice weekly 1
• Has two or more attacks per month producing disability lasting 3+ days 1
• Experiences contraindication to or failure of acute treatments 1
• Has uncommon migraine conditions 1

First-Line Preventive Options

• Propranolol 80-240 mg/day or timolol 20-30 mg/day have consistent evidence of efficacy. 1
• Topiramate and amitriptyline 30-150 mg/day are alternatives, though topiramate has teratogenic potential. 1

Medications to Absolutely Avoid

• Never use opioids (hydromorphone, meperidine) or butalbital-containing compounds for headache treatment, as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time. 1
• These should only be reserved for cases where all other medications are contraindicated, sedation effects are not a concern, and risk for abuse has been addressed. 1

Special Considerations

If Significant Nausea/Vomiting Present

• Choose non-oral routes: intranasal sumatriptan 5-20 mg, subcutaneous sumatriptan 6 mg, or IV therapy with metoclopramide 10 mg IV plus ketorolac 30 mg IV. 1

If Cardiovascular Disease or Contraindications to Triptans

• Use gepants (ubrogepant or rimegepant) as they have no vasoconstrictor activity. 1
• Alternatively, consider dihydroergotamine (DHE) intranasal or IV, which has good evidence for efficacy as monotherapy. 1

Pregnancy Considerations

• If the patient is pregnant, use only acetaminophen 1000 mg as first-line, as it is the safest option during pregnancy. 3
• NSAIDs can be used only during the second trimester. 3
• Avoid NSAIDs at ≥30 weeks gestation due to risk of premature closure of fetal ductus arteriosus. 2
• Metoclopramide 10 mg is safe for migraine-associated nausea, particularly in second and third trimesters. 3

Common Pitfalls to Avoid

1. Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy while optimizing acute treatment strategy. 1

2. Do not abandon triptan therapy after a single failed attempt—if one triptan is ineffective, try a different triptan, as failure of one does not predict failure of others. 1

3. Ensure early administration of medications, as they are most effective when taken early in the attack while headache is still mild. 1

4. Monitor for red flags requiring urgent neuroimaging: positional headache worse when lying down, failure to respond to multiple therapeutic mechanisms, unilateral frontal-to-occipital distribution, or headache worsened by Valsalva's maneuver. 4