What are the recommended treatments for cephalgia (headaches)?

Treatment of Cephalgia (Headache)

For acute episodic migraine headaches, start with combination therapy of a triptan plus an NSAID or acetaminophen, as this provides superior efficacy compared to monotherapy and should be initiated as early as possible after headache onset. 1

Migraine Headache Treatment Algorithm

First-Line Treatment for Mild to Moderate Migraine

• NSAIDs are the initial treatment of choice for mild to moderate migraine attacks 1, 2
• Specific options include:
  • Ibuprofen 400-800 mg every 6 hours 3
  • Naproxen sodium 275-550 mg every 2-6 hours 3
  • Aspirin 650-1000 mg every 4-6 hours (avoid in children/adolescents due to Reye's syndrome risk) 3
• Acetaminophen 1000 mg can be used alone but is generally less effective than NSAIDs 1, 3
• Aspirin-acetaminophen-caffeine combination is strongly recommended for migraine-like headaches, as caffeine provides synergistic analgesia 3, 2

First-Line Treatment for Moderate to Severe Migraine

• Combination therapy with a triptan plus an NSAID or acetaminophen is the preferred approach 1
• Oral triptans with strong evidence include:
  • Sumatriptan 50-100 mg (61-62% achieve headache response at 2 hours) 4
  • Rizatriptan 1
  • Zolmitriptan 1
  • Naratriptan 1
• Begin treatment as soon as possible after headache onset to maximize efficacy 1, 2

Treatment for Severe Migraine with Nausea/Vomiting

• Use non-oral triptan formulations when significant nausea or vomiting is present 1, 2
• Options include:
  • Subcutaneous sumatriptan 6 mg (59% achieve complete pain relief by 2 hours—highest efficacy) 2, 4
  • Intranasal sumatriptan 5-20 mg 2
  • Intranasal zolmitriptan 5-10 mg 1, 2
• Add an antiemetic such as metoclopramide 10 mg for synergistic analgesia and nausea control 3, 2

Second-Line Options for Inadequate Response

• Consider CGRP antagonists (gepants) if combination therapy with triptan plus NSAID fails 1:
  • Rimegepant 1
  • Ubrogepant 1
  • Zavegepant 1
• Ergot alkaloid dihydroergotamine (DHE) is an alternative for patients with contraindications to NSAIDs 1, 2
• Lasmiditan (ditan) should be considered only after all other pharmacologic treatments have failed 1

Intravenous Treatment for Severe Migraine (Urgent Care/ED Setting)

• The most effective IV combination is metoclopramide 10 mg plus ketorolac 30 mg 2
• Ketorolac provides rapid onset with approximately 6 hours duration and minimal rebound headache risk 2
• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy 2

Tension-Type Headache Treatment

Acute Treatment

• Ibuprofen 400 mg or acetaminophen 1000 mg are recommended first-line for short-term treatment 1
• NSAIDs are generally more effective than acetaminophen alone 3, 5
• Aspirin 1000 mg reduces rescue medication use (NNTp 6.0) compared to placebo 5

Preventive Measures

• Physical therapy is recommended for management of tension-type headache 1
• Aerobic exercise or progressive strength training helps prevent tension-type headaches 1

Cluster Headache Treatment

Acute/Abortive Treatment

• Subcutaneous sumatriptan 6 mg or intranasal zolmitriptan 10 mg are first-line for acute cluster attacks 1, 6
• Normobaric oxygen therapy is highly effective for short-term treatment 1
• Noninvasive vagus nerve stimulation can be used for episodic cluster headache 1

Preventive Treatment

• Galcanezumab is recommended for episodic cluster headache prevention 1
• Avoid galcanezumab for chronic cluster headache (weak recommendation against) 1
• Verapamil (at least 240 mg/day) is commonly used but has insufficient evidence for formal recommendation 1, 6
• Alternative preventive options include lithium carbonate 800-1600 mg/day, methylergonovine 0.4-1.2 mg/day, and topiramate 100-200 mg/day 6

Critical Contraindications and Warnings

Medications to AVOID

• Do NOT use opioids or butalbital for acute episodic migraine treatment 1
  • These lead to dependency, rebound headaches, and loss of efficacy 3, 2
  • Reserve opioids only when all other options are contraindicated and abuse risk has been addressed 2

Medication Overuse Headache Prevention

• Limit acute headache medication use to no more than 2 days per week 1, 3
• Medication overuse headache is defined as headache occurring ≥15 days/month for ≥3 months due to medication overuse 1
• Thresholds vary by medication:
  • NSAIDs: ≥15 days per month 1
  • Triptans: ≥10 days per month 1
• If episodic migraine occurs frequently or treatment provides inadequate response, add preventive medications 1

Triptan Safety Considerations

• Perform cardiovascular evaluation before prescribing triptans in patients with multiple cardiovascular risk factors (increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) 4
• Triptans are contraindicated in patients with:
  • Coronary artery disease 4
  • Prinzmetal's angina 4
  • Uncontrolled hypertension 4
  • History of stroke or TIA 4
  • Wolff-Parkinson-White syndrome 4
• Monitor for serotonin syndrome when combining triptans with SSRIs, SNRIs, TCAs, or MAO inhibitors 4

Special Populations

Pregnancy and Breastfeeding

• Discuss adverse effects of pharmacologic treatments during pregnancy and lactation with patients of childbearing potential 1
• Acetaminophen is generally the safer alternative when NSAIDs are contraindicated 3

Patients with Contraindications to NSAIDs

• Use acetaminophen 1000 mg as first-line 3
• Consider dihydroergotamine as an alternative 2
• Avoid aspirin in patients with bleeding disorders or GI bleeding history 2

Lifestyle Modifications

• Counsel all patients on lifestyle modifications 1:
  • Stay well hydrated 1
  • Maintain regular meals 1
  • Secure sufficient and consistent sleep 1
  • Engage in regular moderate to intense aerobic exercise 1
  • Manage stress with relaxation techniques or mindfulness practices 1
  • Pursue weight loss if overweight or obese 1
  • Explore and avoid modifiable migraine triggers 1

Cost Considerations

• Prescribe less costly recommended medications when possible 1
• Over-the-counter medications (acetaminophen, ibuprofen, naproxen, aspirin) are cost-effective first-line options for mild-to-moderate attacks 7
• CGRP antagonists have significantly higher costs (annualized WAC $4,959-$8,800) compared to triptans and NSAIDs 1