What medications are recommended for a patient experiencing headaches?

Medications for Headache Treatment

First-Line Acute Treatment

For mild to moderate headaches, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 900-1000 mg) or acetaminophen 1000 mg, and escalate to triptans (sumatriptan 50-100 mg, rizatriptan 10 mg, or others) for moderate to severe attacks or when NSAIDs fail. 1

NSAIDs and Acetaminophen

• Naproxen sodium 500-825 mg is the preferred first-line NSAID due to strong efficacy evidence and favorable safety profile 1
• Ibuprofen 400-800 mg and aspirin 900-1000 mg are acceptable alternatives with similar efficacy 1, 2
• Acetaminophen 1000 mg is effective but sits at the lower end of the efficacy spectrum compared to NSAIDs 1, 3
• The combination of aspirin 250 mg + acetaminophen 250 mg + caffeine 65 mg provides synergistic analgesia and is recommended when patients respond poorly to single-agent NSAIDs 1

Triptans for Moderate to Severe Attacks

• Sumatriptan 50-100 mg orally achieves headache response (reduction to mild or no pain) in 52-62% of patients at 2 hours and 65-79% at 4 hours 4
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan 1
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes, ideal for severe attacks or when nausea/vomiting is present 1, 4
• Intranasal sumatriptan 5-20 mg is particularly useful when significant nausea or vomiting prevents oral administration 1
• If one triptan fails after 2-3 headache episodes, try a different triptan, as failure of one does not predict failure of others 1

Combination Therapy for Enhanced Efficacy

The combination of triptan + NSAID (e.g., sumatriptan 50-100 mg + naproxen 500 mg) is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours. 1

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg IV or oral provides direct analgesic effects through central dopamine receptor antagonism, beyond just treating nausea 1
• Prochlorperazine 10 mg (oral or IV) is comparable in efficacy to metoclopramide with a more favorable side effect profile (21% vs 50% adverse events) 1
• Add antiemetics 20-30 minutes before the analgesic for synergistic benefit 1

IV Treatment for Severe Migraine

For severe migraine requiring IV treatment, use metoclopramide 10 mg IV plus ketorolac 30 mg IV as first-line combination therapy. 1

• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 1
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy 1
• Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide 1

Critical Frequency Limitation

Limit ALL acute migraine 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

• Medication-overuse headache develops with frequent use: ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1
• If using acute medications more than twice weekly, initiate preventive therapy immediately 1

Preventive Therapy Indications

Preventive therapy should be initiated for patients with: 5

• Two or more migraine attacks per month producing disability lasting 3+ days
• Use of abortive medication more than twice per week
• Contraindication to or failure of acute treatments
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction)

First-Line Preventive Medications

• Propranolol 80-240 mg/day or timolol 20-30 mg/day (beta-blockers without intrinsic sympathomimetic activity) 5
• Topiramate 50-100 mg/day (particularly useful for patients with obesity due to weight loss benefits) 5
• Candesartan (particularly useful for patients with comorbid hypertension) 5

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day (optimal for patients with comorbid depression or anxiety) 5
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day (strictly contraindicated in women of childbearing potential due to teratogenic effects) 5

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection for patients who have failed 2-3 oral preventive medications 5
• Efficacy assessment requires 3-6 months 5

Medications to Avoid

Absolutely avoid opioids (hydromorphone, oxycodone) and butalbital-containing compounds for acute migraine treatment, as they lead to medication-overuse headache, dependency, and loss of efficacy over time. 1

• Opioids should be reserved only for cases where other medications cannot be used, when sedation effects are not a concern, or when the risk for abuse has been addressed 1
• Ergotamine (Cafergot) carries substantial risks including myocardial infarction, vasospastic ischemia, and ergot poisoning with chronic use, and receives a lower efficacy rating (3/4) compared to triptans (4/4) 1, 6

Contraindications and Safety Considerations

Triptan Contraindications

• Ischemic heart disease or previous myocardial infarction 4
• Uncontrolled hypertension 4
• Cerebrovascular disease (history of stroke or TIA) 4
• Wolff-Parkinson-White syndrome or arrhythmias with cardiac accessory conduction pathways 4
• Pregnancy (Category X for ergotamine) 6

NSAID Precautions

• Use with caution in renal impairment (creatinine clearance <30 mL/min) 1
• Avoid in aspirin/NSAID-induced asthma or active GI bleeding 1
• Monitor for cardiovascular risk with prolonged use 1

Alternative Newer Agents

CGRP Antagonists (Gepants)

• Ubrogepant 50-100 mg or rimegepant are the primary oral alternatives when triptans are contraindicated (e.g., cardiovascular disease, uncontrolled hypertension) 1
• Gepants have no vasoconstriction, making them safe for patients with cardiovascular contraindications to triptans 1
• Eliminate headache symptoms for 2 hours in 20% of patients with adverse effects of nausea and dry mouth in 1-4% 7

Ditans (Lasmiditan)

• Lasmiditan 50-200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity 1
• Safe alternative for patients with cardiovascular disease 1
• Patients must not drive or operate machinery for at least 8 hours after taking lasmiditan due to CNS effects (dizziness, vertigo, somnolence, fatigue) 1

Treatment Algorithm Summary

1. Mild to moderate headache: Start with NSAID (naproxen 500-825 mg, ibuprofen 400-800 mg) or acetaminophen 1000 mg 1
2. Moderate to severe headache: Use triptan (sumatriptan 50-100 mg, rizatriptan 10 mg) + NSAID for synergistic effect 1
3. Severe headache with nausea/vomiting: Subcutaneous sumatriptan 6 mg or intranasal formulation 1
4. IV treatment for severe attacks: Metoclopramide 10 mg IV + ketorolac 30 mg IV 1
5. If triptans contraindicated: Use gepants (ubrogepant, rimegepant) or lasmiditan 1
6. If using acute medications >2 days/week: Initiate preventive therapy immediately 1, 5