What are the recommended treatments for headaches?

Headache Treatment

For acute migraine headaches, start with combination therapy of a triptan plus an NSAID or acetaminophen, which provides superior efficacy compared to either agent alone and represents the strongest evidence-based recommendation for moderate to severe attacks. 1

Treatment Algorithm by Headache Type and Severity

Migraine Headaches

Mild to Moderate Migraine

• First-line: NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) OR acetaminophen 1000 mg 1
• Ibuprofen 400 mg provides 2-hour headache relief in 57% of patients versus 25% with placebo (NNT 3.2) 2
• Acetaminophen 1000 mg provides 2-hour headache relief in 56% of patients versus 36% with placebo (NNT 5.0) 3

Moderate to Severe Migraine

• First-line: Combination therapy with a triptan PLUS an NSAID or acetaminophen 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 4
• This combination should be initiated as soon as possible after migraine onset, ideally when pain is still mild 1

Severe Migraine with Nausea/Vomiting

• Use non-oral routes: Subcutaneous sumatriptan 6 mg (provides pain relief in 70-82% within 15 minutes) OR intranasal zolmitriptan 1, 4
• Add antiemetic: Metoclopramide 10 mg IV or prochlorperazine 10 mg IV for both antiemetic and direct analgesic effects 1, 4

Second-Line Options (When First-Line Fails or Contraindicated)

• CGRP antagonists (gepants): Rimegepant, ubrogepant, or zavegepant for patients who do not tolerate or have inadequate response to triptan-NSAID combination 1
• Lasmiditan: Consider only after all other pharmacologic treatments have failed 1
• Dihydroergotamine (DHE): Intranasal or IV formulation as alternative 1, 4

Tension-Type Headaches

Acute Treatment

• First-line: Ibuprofen 400 mg OR acetaminophen 1000 mg 1, 5
• Both medications show significant improvement at 2 hours compared to placebo 1

Chronic Tension-Type Headache Prevention

• First-line: Amitriptyline 30-150 mg/day 1, 5
• Avoid: Botulinum toxin injections (weak recommendation against) 1

Cluster Headaches

Acute Treatment

• First-line: Subcutaneous sumatriptan 6 mg OR intranasal zolmitriptan 10 mg 1, 5
• Alternative: Normobaric oxygen therapy 1

Prevention

• Episodic cluster: Galcanezumab 1, 5
• Chronic cluster: Galcanezumab is NOT recommended 1

Critical Frequency Limitations to Prevent Medication-Overuse Headache

Limit ALL acute migraine medications to no more than 2 days per week. 1, 4

• NSAIDs: Maximum 15 days per month 1
• Triptans: Maximum 10 days per month 1
• Exceeding these thresholds leads to medication-overuse headache, defined as headache occurring on 15+ days per month for at least 3 months 1
• If patients require acute treatment more than twice weekly, initiate preventive therapy immediately 4

Medications to AVOID

Do NOT use opioids or butalbital-containing compounds for acute episodic migraine. 1

• These medications lead to dependency, rebound headaches, and eventual loss of efficacy 4
• Opioids should only be reserved for cases where all other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 4

IV "Headache Cocktail" for Emergency/Urgent Care Settings

Optimal combination: Metoclopramide 10 mg IV PLUS ketorolac 30 mg IV 4

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism beyond its antiemetic properties 4
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 4
• This combination is superior to prednisone, which has limited evidence for acute headache treatment 4

Special Populations

Pregnancy and Breastfeeding

• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation with patients of childbearing potential 1
• Treatment selection must weigh maternal benefit against fetal/infant risk 1

Cardiovascular Contraindications

• Triptans are contraindicated in patients with ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 4, 6
• Consider CGRP antagonists or DHE as alternatives in these patients 1

When to Initiate Preventive Therapy

Preventive medications are warranted when: 1

• Episodic migraine occurs frequently (≥2 attacks per month producing disability lasting ≥3 days)
• Acute treatment does not provide adequate response
• Patient uses abortive medication more than twice per week
• Contraindication to or failure of acute treatments exists

Essential Lifestyle Modifications

Counsel all patients on: 1

• Staying well hydrated and maintaining regular meals
• Securing sufficient and consistent sleep (7-9 hours)
• Engaging in regular moderate to intense aerobic exercise
• Managing stress with relaxation techniques or mindfulness practices
• Weight loss for those who are overweight or obese
• Identifying and avoiding modifiable migraine triggers

Cost Considerations

Prescribe less costly recommended medications when equally effective. 1

• Generic NSAIDs and triptans are significantly less expensive than newer CGRP antagonists 1
• Annualized cost of oral gepants: $4,959-$5,994 versus generic sumatriptan: <$100 1
• Cost-effectiveness favors triptan-NSAID combination as first-line therapy 1