What are the recommended treatments for headaches and pain syndromes?

Recommended Treatments for Headaches and Pain Syndromes

Acute Episodic Migraine Treatment Algorithm

For moderate to severe migraine, start with combination therapy of a triptan plus an NSAID (or acetaminophen if NSAIDs are contraindicated), as this provides superior efficacy compared to either agent alone and represents the strongest evidence-based approach. 1

First-Line Treatment for Mild to Moderate Migraine

• Begin with NSAIDs as monotherapy: ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg 1
• Acetaminophen 1000 mg can be used as an alternative when NSAIDs are contraindicated, though it is less effective when used alone 1, 2
• The combination of aspirin 500 mg + acetaminophen 500 mg + caffeine 130 mg has strong evidence for efficacy 1
• Critical timing: Instruct patients to take medication as soon as the headache begins while pain is still mild, as early treatment significantly improves efficacy 1

Escalation to Combination Therapy for Moderate to Severe Migraine

• If NSAIDs alone provide insufficient relief, add a triptan to the NSAID regimen (or to acetaminophen when NSAIDs are contraindicated) 1
• Specific triptan options with strong evidence include: sumatriptan 50-100 mg, rizatriptan, zolmitriptan, naratriptan, eletriptan, almotriptan, or frovatriptan 1
• The combination of triptan + NSAID is superior to either agent alone: 130 more patients per 1000 achieve sustained pain relief at 48 hours compared to monotherapy 3
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes for patients with rapid progression or severe nausea/vomiting 1, 3, 4

Third-Line Options When Combination Therapy Fails

• CGRP antagonists (gepants): rimegepant, ubrogepant, or zavegepant for patients who do not tolerate or have inadequate response to triptan + NSAID combination 1
• Dihydroergotamine (DHE): intranasal or IV formulation has good evidence for efficacy as monotherapy 1
• Lasmiditan (ditan): reserve for patients who have failed all other pharmacologic treatments in this guideline 1

Management of Associated Symptoms

• For nausea/vomiting: Add metoclopramide 10 mg IV or prochlorperazine 10 mg IV, which provide direct analgesic effects beyond antiemetic properties 1, 3
• Consider non-oral routes (subcutaneous, intranasal, IV) when significant nausea or vomiting is present early in the attack 1
• Antiemetics should not be restricted only to patients who are vomiting, as nausea itself is one of the most disabling symptoms and warrants treatment 1, 3

Critical Medication Frequency Limits

Limit ALL acute migraine medications to no more than 2 days per week to prevent medication-overuse headache (MOH), which paradoxically increases headache frequency and can lead to daily headaches. 1, 3

• Medication overuse headache is defined as headache occurring ≥15 days per month for at least 3 months in patients with preexisting headache disorder 1, 4
• The threshold varies by medication: ≥10 days/month for triptans, ≥15 days/month for NSAIDs 1, 3
• If patients require acute treatment more than twice weekly, immediately initiate preventive therapy 1, 3

Medications to Avoid

Never use opioids or butalbital-containing compounds for acute episodic migraine, as they lead to dependency, rebound headaches, and eventual loss of efficacy without providing superior pain relief. 1, 3, 5

Preventive Therapy Indications

Initiate preventive therapy when patients meet any of the following criteria 1, 3:

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

First-Line Preventive Medications

• Beta-blockers: propranolol 80-240 mg/day or timolol 20-30 mg/day 1, 3
• Tricyclic antidepressants: amitriptyline 30-150 mg/day (particularly effective for mixed migraine and tension-type headache) 1, 3
• Anticonvulsants: divalproex sodium 500-1500 mg/day, sodium valproate 800-1500 mg/day, or topiramate 1
• Newer options: CGRP monoclonal antibodies (galcanezumab, fremanezumab, eptinezumab, erenumab) or atogepant 1, 3
• Other options: angiotensin-receptor blockers, lisinopril, magnesium, or memantine 1

Chronic Migraine Prevention

• OnabotulinumtoxinA can be used for prevention of chronic migraine (≥15 headache days per month) but NOT for episodic migraine 1
• Gabapentin is NOT recommended for prevention of episodic migraine 1

Tension-Type Headache (TTH) Treatment

• Acute treatment: ibuprofen 400 mg or acetaminophen 1000 mg 1, 5
• Prevention of chronic TTH: amitriptyline 1
• Non-pharmacologic options: physical therapy or aerobic exercise 1, 5

Special Populations

Pregnancy and Lactation

• Discuss adverse effects of pharmacologic treatments during pregnancy and lactation before initiating therapy 1
• Valproate is strictly contraindicated due to teratogenic risk 1, 3
• Sumatriptan is contraindicated in pregnant patients 1, 4

Cardiovascular Contraindications

Triptans are contraindicated in patients with 1, 4:

• Ischemic coronary artery disease or coronary vasospasm (Prinzmetal's angina)
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
• History of stroke or transient ischemic attack
• Uncontrolled hypertension
• Peripheral vascular disease

Non-Pharmacologic Adjuncts

• Aerobic exercise: graded increases in intensity performed at least once weekly for 4 weeks 5
• Physical therapy: particularly when cervicogenic features are present 1, 5
• Behavioral interventions: biofeedback and relaxation training as first-line preventive options 3
• Acupuncture: potential first-line intervention based on recent positive randomized trial findings 3

Common Pitfalls to Avoid

• Do not wait for pain to become severe before treating: early treatment while pain is mild significantly improves medication efficacy 1, 3, 5
• Do not allow patients to increase frequency of acute medication use in response to treatment failure: this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy 3
• Do not assume failure of one triptan predicts failure of all triptans: patients who do not respond to one triptan may respond to another within the same class 1, 3
• Do not restrict antiemetics only to patients who are vomiting: nausea itself is disabling and should be treated appropriately 1, 3