What are the treatment options for migraines?

Migraine Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with combination therapy of an NSAID plus acetaminophen, or use acetaminophen/aspirin/caffeine combination; for moderate to severe attacks or inadequate response to first-line therapy, escalate immediately to a triptan combined with an NSAID. 1, 2

First-Line Acute Treatment

• Begin treatment as soon as possible after migraine onset using combination therapy for maximum efficacy. 1, 2
• For mild to moderate attacks, use NSAIDs (aspirin, ibuprofen, diclofenac potassium) combined with acetaminophen, or the fixed-dose combination of acetaminophen/aspirin/caffeine. 1, 2
• Acetaminophen 1000 mg monotherapy is less effective than NSAIDs or combination therapy and should be reserved for patients intolerant of NSAIDs. 1

Second-Line Acute Treatment (Triptans)

• Offer triptans to patients for whom over-the-counter analgesics provide inadequate relief. 1
• Triptans are most effective when taken early while headache is still mild. 1
• Combine a triptan with an NSAID or acetaminophen to improve efficacy beyond either agent alone. 1
• If one triptan fails, trial other triptans as they may still provide relief. 1
• For patients with severe nausea or vomiting preventing oral intake, use subcutaneous sumatriptan injection or non-oral triptan formulations. 1, 3

Third-Line Acute Treatment

• For patients who fail all available triptans or have contraindications (coronary artery disease, uncontrolled hypertension, recent cardiovascular events), escalate to CGRP antagonists (gepants) like rimegepant, ubrogepant, or zavegepant; dihydroergotamine; or lasmiditan. 1, 2
• Lasmiditan should be considered only after failure of all other pharmacologic treatments. 2

Managing Associated Symptoms

• Use non-oral routes of administration for patients with migraine-associated nausea/vomiting. 1
• Add antiemetics like metoclopramide or prochlorperazine to treat nausea and improve gastric motility, enhancing absorption of oral medications. 1

Emergency/Urgent Care Setting

• For severe migraine requiring parenteral therapy, use IV ketorolac 30 mg plus IV metoclopramide 10 mg as first-line combination therapy. 2

Critical Medications to Avoid

• Avoid opioids and butalbital-containing analgesics for migraine treatment due to questionable efficacy, adverse effects, and risk of dependency. 1, 2

Medication Overuse Headache Prevention

• Limit acute medication use to ≤10 days per month for triptans and ≤15 days per month for NSAIDs to prevent medication overuse headache. 1, 2
• Initiate preventive therapy if acute treatment is needed more than 2 days per week. 2

Preventive Treatment

Indications for Preventive Therapy

• Consider preventive therapy for patients with: 1
  • Two or more attacks per month producing disability lasting 3+ days per month
  • Contraindication to or failure of acute treatments
  • Use of acute medication more than twice per week
  • Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura)

First-Line Preventive Medications

• Topiramate is effective for preventive treatment but requires discussion of teratogenic effects with patients of childbearing potential. 1
• Beta-blockers: metoprolol, propranolol, and timolol are established as effective first-line options. 4
• Divalproex is established as effective first-line therapy. 4

Second-Line Preventive Medications

• Amitriptyline, venlafaxine, atenolol, and nadolol are probably effective but should be second-line therapy. 4
• Consider an ACE inhibitor (lisinopril), ARB (candesartan), or SSRI if first-line treatments are not tolerated or result in inadequate response. 1

Newer Preventive Agents

• CGRP receptor monoclonal antibodies (erenumab, galcanezumab) are FDA-approved for migraine prevention and represent a major advance, particularly for patients who have failed multiple traditional preventive medications. 5, 6
• OnabotulinumtoxinA 155 units is FDA-approved and effective specifically for chronic migraine (≥15 headache days per month), but is ineffective for episodic migraine. 7

Preventive Therapy Management

• Start preventive medications at a low dose and gradually increase until desired outcomes are achieved. 1
• Monitor treatment using a headache diary to determine efficacy, identify analgesic overuse, and follow migraine progression. 1
• Switch preventive treatment if an adequate response is not achieved during a reasonable trial period (typically 2-3 months at therapeutic dose). 1

Non-Pharmacologic Treatments

Behavioral Therapies

• Offer cognitive-behavioral therapy, biofeedback, and relaxation training to all patients as these have good evidence for efficacy and should be part of comprehensive management. 7, 1
• Relaxation training, progressive muscle relaxation, and visualization/guided imagery provide relief for many patients. 7

Essential Lifestyle Modifications

• Maintain regular meals, stay well hydrated, and ensure sufficient sleep with consistent sleep-wake times. 1, 2
• Engage in regular moderate to intense aerobic exercise (40 minutes three times weekly is as effective as some preventive medications). 7, 1
• Manage stress with relaxation techniques or mindfulness practices. 1, 2
• Identify and reduce aggravating factors and triggers using a headache diary. 7
• Weight loss if overweight or obese. 2

Special Populations

Pregnancy and Breastfeeding

• Acetaminophen is first-line treatment for pregnant or breastfeeding patients. 2
• NSAIDs are usable prior to the third trimester but should be avoided in the third trimester. 2

Chronic Migraine Management

Definition and Approach

• Chronic migraine is defined as ≥15 headache days per month. 7
• Rule out secondary causes of headache before establishing chronic migraine diagnosis. 7
• Limit as-needed medication use and monitor closely for medication overuse headache. 7
• Consider and treat comorbid conditions (depression, anxiety, hypertension) appropriately as they may worsen migraine burden. 7
• OnabotulinumtoxinA is specifically FDA-approved and effective for chronic migraine based on large-scale, double-blind, placebo-controlled trials. 7

Multidisciplinary Approach

• Chronic migraine requires collaboration between primary care physicians and headache specialists. 7
• Establish realistic expectations as improvement may be gradual, but achievable in the majority of patients. 7
• Use validated tools like the Headache Impact Test-6 (HIT-6) and Migraine-Specific Quality-of-Life Questionnaire (MSQ) to monitor treatment response. 7

Cost Considerations

• Prescribe less costly recommended medications when equally effective options exist, with generic NSAIDs and older triptans (sumatriptan, naratriptan) being significantly less expensive than newer agents. 2