What medications are used to treat headaches?

Medications for Headache Treatment

First-Line Acute Treatment

For mild to moderate headaches, NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 500-1000 mg) are the recommended first-line treatment, while triptans are first-line for moderate to severe migraine attacks. 1

NSAIDs and Acetaminophen

• Ibuprofen 400 mg provides 2-hour headache relief in 57% of patients versus 25% with placebo (NNT 3.2), and 2-hour pain-free response in 26% versus 12% (NNT 7.2). 1, 2
• Ibuprofen 400 mg is significantly more effective than 200 mg for 2-hour headache relief, making the higher dose preferable. 1
• Naproxen sodium 500-825 mg should be taken at migraine onset when pain is still mild, and can be repeated every 2-6 hours with a maximum of 1.5 g per day. 1
• Acetaminophen 1000 mg is effective for tension-type headaches and mild migraines, though clinically similar to aspirin 650 mg in head-to-head comparisons. 1, 3
• The combination of aspirin-acetaminophen-caffeine has strong evidence for moderate to severe migraine, with caffeine providing synergistic analgesia by enhancing absorption and efficacy of analgesics. 1

Triptans for Moderate to Severe Migraine

• Oral triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan) are first-line therapy for moderate to severe migraine attacks. 1
• Subcutaneous sumatriptan 6 mg is the most effective and rapidly acting option, providing pain relief in 70-82% of patients within 15 minutes and complete pain-free response in 59% by 2 hours. 1
• Intranasal sumatriptan (5-20 mg) is particularly useful when significant nausea or vomiting is present. 1
• Triptans work through 5-HT1B/1D receptor agonism, causing cranial vessel constriction and inhibiting pro-inflammatory neuropeptide release. 4

Antiemetics as Adjunctive or Monotherapy

Antiemetics provide both anti-nausea effects and direct analgesic benefits for migraine through central dopamine receptor antagonism. 1

• Metoclopramide 10 mg IV or oral provides synergistic analgesia for migraine pain, not just nausea relief, and should not be restricted only to patients who are vomiting. 1
• Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide in efficacy, with a more favorable side effect profile (21% adverse events versus 50% with chlorpromazine). 1
• Adding an antiemetic 20-30 minutes before NSAIDs improves outcomes compared to NSAIDs alone. 1

Intravenous Treatment for Severe Migraine

For severe migraine requiring IV treatment, the combination of metoclopramide 10 mg IV plus ketorolac 30 mg IV is first-line therapy, providing rapid pain relief while minimizing rebound headache risk. 1

• Ketorolac has rapid onset with approximately 6 hours duration and minimal risk of rebound headache. 1
• Prochlorperazine 10 mg IV is an effective alternative to metoclopramide. 1
• Intranasal or IV dihydroergotamine (DHE) has good evidence for efficacy and safety as monotherapy for acute migraine. 1

Critical Medication Overuse Warning

Limit all acute headache medications to no more than twice weekly to prevent medication-overuse headache, which causes increasing headache frequency and potentially daily headaches. 1

• This applies to NSAIDs, triptans, combination analgesics, and especially opioids or butalbital-containing compounds. 1
• Opioids (including hydromorphone) should be reserved only for cases where other medications cannot be used, when sedation is not a concern, or when abuse risk has been addressed—they lead to dependency, rebound headaches, and loss of efficacy. 1

When to Escalate Treatment

If a patient's current medication stops working, first try a different triptan (failure of one does not predict failure of others), ensure early administration during attacks, or add combination therapy with fast-acting NSAIDs. 1

• Consider route change (e.g., subcutaneous sumatriptan if oral fails), particularly for patients with rapid peak intensity or vomiting. 1
• If headaches occur more than 2 days per week despite optimized acute therapy, initiate preventive therapy rather than increasing acute medication frequency. 1

Preventive Therapy Indications

Preventive therapy should be considered for patients experiencing ≥2 migraine attacks per month with disability lasting ≥3 days per month, or those using abortive medications more than twice weekly. 5

First-Line Preventive Medications

• Propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day in divided doses), and candesartan are first-line preventive agents with strong evidence. 5
• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit increases, with an adequate trial period of 2-3 months. 5

Second-Line Preventive Options

• Amitriptyline (30-150 mg/day) is particularly effective for patients with mixed migraine and tension-type headache. 5
• Valproate/divalproex sodium (800-1500 mg/day) is effective but strictly contraindicated in women of childbearing potential due to teratogenic effects. 5

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, galcanezumab, or eptinezumab should be considered when first- and second-line treatments have failed or are contraindicated, with efficacy assessed after 3-6 months. 5

Special Considerations for Patients on Warfarin

For patients on warfarin, triptans and acetaminophen are safe first-line options, while NSAIDs should be avoided due to significantly increased bleeding risk. 6

• CGRP antagonists (rimegepant, ubrogepant) are safe alternatives for patients who do not tolerate triptans. 6
• The aspirin-acetaminophen-caffeine combination requires increased PT/INR monitoring due to aspirin's antiplatelet effects. 6