What are the treatment options for a patient experiencing migraines?

Migraine Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or the combination of aspirin-acetaminophen-caffeine; for moderate to severe attacks or when NSAIDs fail, escalate immediately to a triptan plus NSAID combination, which provides superior efficacy compared to either agent alone. 1, 2

First-Line Treatment by Attack Severity

Mild to Moderate Attacks:

• NSAIDs are the primary first-line option, with ibuprofen, naproxen sodium, aspirin, and diclofenac potassium having the strongest evidence 1, 2, 3
• The aspirin-acetaminophen-caffeine combination achieves pain freedom in 1 out of 9 patients at 2 hours (NNT=9) and pain relief in 1 out of 4 patients (NNT=4) 2
• Acetaminophen 1000 mg has less efficacy than NSAIDs and should only be used when NSAIDs are contraindicated 2, 3
• Take medication immediately at migraine onset while pain is still mild to maximize effectiveness 1, 2

Moderate to Severe Attacks:

• Triptans combined with NSAIDs represent the gold standard, with 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 1, 2
• Oral triptans with strong evidence include sumatriptan 50-100 mg, rizatriptan, naratriptan, and zolmitriptan 1, 4
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes, making it ideal for rapidly progressive attacks or when vomiting prevents oral medication 1, 3
• If one triptan fails, try a different triptan before abandoning the class entirely, as failure of one does not predict failure of others 1, 2

Managing Nausea and Vomiting

• Add metoclopramide 10 mg or prochlorperazine 10 mg 20-30 minutes before analgesics, as these provide direct analgesic effects through central dopamine receptor antagonism beyond their antiemetic properties 1, 3
• Use non-oral routes (IV, intranasal, rectal) when significant nausea or vomiting is present early in the attack 1, 2
• Intranasal sumatriptan 5-20 mg is particularly useful when oral administration is not feasible 1

Alternative Acute Medications When Triptans Fail or Are Contraindicated

CGRP Antagonists (Gepants) - Primary Alternative:

• Ubrogepant 50-100 mg or rimegepant are the preferred alternatives when triptans are contraindicated due to cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 1, 2
• These have no vasoconstriction and achieve pain freedom in 1 out of 13 patients at 2 hours (NNT=13) 2

Ditans - Secondary Alternative:

• Lasmiditan 50-200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, making it safe for cardiovascular disease patients 1, 2
• Critical warning: Patients cannot drive or operate machinery for at least 8 hours after taking lasmiditan due to CNS effects (dizziness, vertigo, somnolence) 1

Dihydroergotamine (DHE):

• Intranasal or IV DHE has good evidence for efficacy as monotherapy 1, 3

Emergency Department/Urgent Care IV Treatment

The optimal IV cocktail consists of:

• Metoclopramide 10 mg IV for direct analgesic effects plus antiemetic properties 1
• Ketorolac 30 mg IV (60 mg IM for patients <65 years) for rapid onset and 6-hour duration with minimal rebound headache risk 1
• Prochlorperazine 10 mg IV is equally effective as metoclopramide with a more favorable side effect profile (21% vs 50% adverse events) 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit ALL acute migraine medications to no more than 2 days per week (10 days per month maximum) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 1, 2, 5

• NSAIDs trigger medication-overuse headache at ≥15 days/month 1
• Triptans trigger medication-overuse headache at ≥10 days/month 1
• If you need acute treatment more than twice weekly, initiate preventive therapy immediately 1, 5

Medications to Absolutely Avoid

Never use opioids or butalbital-containing compounds for acute migraine treatment, as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1, 2, 6

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Preventive Treatment

Indications for Preventive Therapy

Initiate preventive therapy when patients experience:

• ≥2 attacks per month producing disability lasting ≥3 days 1, 5, 7
• Use of acute medications more than twice weekly 1, 5
• Contraindication to or failure of acute treatments 5, 7
• Presence of uncommon migraine variants (hemiplegic migraine, migraine with prolonged aura) 2, 5

First-Line Preventive Medications

For Episodic Migraine (<15 headache days/month):

• Beta-blockers without intrinsic sympathomimetic activity: Propranolol 80-240 mg/day or timolol 20-30 mg/day have the most consistent evidence 1, 5, 7
• Topiramate 50-200 mg/day has documented high efficacy but requires discussion of teratogenic effects with patients of childbearing potential 2, 5, 7
• Amitriptyline 30-150 mg/day is particularly effective for patients with mixed migraine and tension-type headache 1, 5, 7
• Divalproex sodium/sodium valproate 500-1500 mg/day, though it has adverse events including weight gain, hair loss, tremor, and is strictly contraindicated in pregnancy due to teratogenic risk 1, 7

For Chronic Migraine (≥15 headache days/month):

• OnabotulinumtoxinA 155 units is the only FDA-approved treatment specifically for chronic migraine, with efficacy demonstrated in large-scale, double-blind, placebo-controlled trials 5
• Topiramate is the only oral medication proven effective in randomized placebo-controlled trials specifically for chronic migraine 5

CGRP Monoclonal Antibodies:

• Consider when oral preventives have failed or are contraindicated, with efficacy assessed after 3-6 months 1

Preventive Medication Principles

• Start at a low dose and gradually increase until desired outcomes are achieved 2, 7
• Give each treatment an adequate trial: 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, 6-9 months for onabotulinumtoxinA 1
• Monitor treatment efficacy using a headache diary 2, 5
• Switch preventive treatment if adequate response (≥50% reduction in attack frequency) is not achieved during a reasonable trial period 2, 5
• Failure of one preventive class does not predict failure of others 1

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Non-Pharmacologic Treatments

Behavioral Therapies:

• Cognitive-behavioral therapy, biofeedback, and relaxation training should be offered to all patients as these have good evidence for efficacy and should be integrated into comprehensive management 5, 6

Exercise:

• Regular moderate-to-intense aerobic exercise for 40 minutes three times weekly is as effective as topiramate or relaxation therapy for migraine prevention 2, 5

Neuromodulation Devices:

• Single-pulse transcranial magnetic stimulation (s-TMS), external trigeminal nerve stimulation (e-TNS), remote electrical neuromodulation (REN), and noninvasive vagus nerve stimulation (nVNS) all have good documentation and safety profiles 6

Lifestyle Modifications:

• Maintain regular meals, stay well hydrated, and ensure sufficient sleep 2
• Manage stress with relaxation techniques or mindfulness practices 2, 5
• Identify and reduce aggravating factors and triggers using a headache diary 2, 5

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Special Populations and Comorbidities

Pregnancy and Lactation:

• Discuss adverse effects of pharmacologic treatments before initiating therapy 1
• Valproate is strictly contraindicated due to teratogenic risk 1

Cardiovascular Disease:

• Triptans are contraindicated in patients with ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 1, 3
• Use gepants or lasmiditan as alternatives 1

Comorbidity Management:

• Treat comorbid conditions with medications that also benefit migraine when possible, such as amitriptyline for depression and migraine, or beta-blockers for hypertension and migraine 5