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 after 2-3 episodes, escalate immediately to a triptan plus NSAID combination, which provides superior efficacy compared to either agent alone. 1, 2, 3

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, 4
• The aspirin-acetaminophen-caffeine combination has a number needed to treat of 9 for pain freedom at 2 hours and 4 for pain relief at 2 hours, making it highly effective 3
• Acetaminophen 1000 mg has less efficacy than NSAIDs and should only be used when NSAIDs are contraindicated 2
• Take medication as early as possible during the attack while pain is still mild to maximize effectiveness 1, 2

Moderate to Severe Attacks:

• Triptans combined with NSAIDs represent the strongest evidence-based approach, with 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 1
• Oral triptans with robust evidence include sumatriptan 50-100 mg, rizatriptan 10 mg, naratriptan, and zolmitriptan 1, 4, 5
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan 1
• If one triptan fails after 2-3 headache episodes, switch to a different triptan, as failure of one does not predict failure of others 1, 2

Route Selection Based on Symptoms

For patients with significant nausea or vomiting:

• Use non-oral routes of administration, as oral absorption is impaired during migraine attacks 1, 2
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes 1, 5
• Intranasal sumatriptan 5-20 mg or intranasal zolmitriptan are effective alternatives 1
• Add antiemetics 20-30 minutes before other medications: metoclopramide 10 mg or prochlorperazine 25 mg provide synergistic analgesia beyond their antiemetic effects 1, 2

Emergency Department/Urgent Care IV Cocktail

The optimal IV combination for severe migraine is metoclopramide 10 mg IV plus ketorolac 30 mg IV, providing rapid pain relief while minimizing rebound headache risk. 1

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, independent of its antiemetic properties 1
• Ketorolac has rapid onset with approximately 6 hours duration and 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
• Dihydroergotamine (DHE) IV or intranasal is an alternative with good evidence for efficacy as monotherapy 1

Advanced Options When Triptans Fail or Are Contraindicated

For patients with triptan contraindications (cardiovascular disease, uncontrolled hypertension, cerebrovascular disease) or triptan failures, gepants are the primary alternative. 1, 2

• Ubrogepant 50-100 mg or rimegepant are CGRP antagonists with no vasoconstriction, making them safe for patients with cardiovascular contraindications 1, 3
• Ubrogepant has a number needed to treat of 13 for pain freedom at 2 hours 3
• Lasmiditan 50-200 mg (5-HT1F agonist) is a second-line alternative without vasoconstrictor activity, but patients cannot drive or operate machinery for at least 8 hours due to CNS effects 1, 6
• Lasmiditan has a number needed to harm of 4 for treatment-emergent adverse effects 3

Critical Frequency Limitations

Limit all acute migraine medications to no more than 2 days per week (10 days per month for triptans, 15 days per month for NSAIDs) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2, 7

• Medication-overuse headache occurs when acute medications are used ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1, 2
• If patients require acute treatment more than twice weekly, initiate preventive therapy immediately 1, 3

Medications to Absolutely Avoid

Never use opioids or butalbital-containing compounds for migraine treatment, as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time. 1, 2, 7

Preventive Therapy Indications

Initiate preventive therapy when patients experience ≥2 attacks per month producing disability lasting ≥3 days, use acute medications more than twice weekly, have contraindications to acute treatments, or suffer from uncommon migraine variants. 2, 3

First-Line Preventive Medications

For episodic migraine:

• Beta-blockers without intrinsic sympathomimetic activity: propranolol 80-240 mg/day or timolol 20-30 mg/day 1, 3
• Topiramate (requires discussion of teratogenic effects with patients of childbearing potential) 2, 3
• Amitriptyline 30-150 mg/day, particularly for patients with mixed migraine and tension-type headache 1, 3

For chronic migraine (≥15 headache days per month):

• OnabotulinumtoxinA 155 units is FDA-approved and specifically effective for chronic migraine based on large-scale, double-blind, placebo-controlled trials 2, 3
• Topiramate is the only oral medication proven effective in randomized placebo-controlled trials specifically for chronic migraine 3

CGRP Monoclonal Antibodies

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

Monitoring and Treatment Duration

• Start preventive medications at a low dose and gradually increase until desired outcomes are achieved 2
• Monitor treatment using a headache diary to determine efficacy, identify analgesic overuse, and follow migraine progression 2, 3
• Assess efficacy after 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA 1
• Switch preventive treatment if adequate response is not achieved during a reasonable trial period 2, 3

Non-Pharmacologic Treatments

Regular moderate-to-intense aerobic exercise for 40 minutes three times weekly is as effective as topiramate or relaxation therapy for migraine prevention. 2, 3

• Cognitive-behavioral therapy, biofeedback, and relaxation training have good evidence for efficacy and should be integrated into comprehensive management 2, 3
• Neuromodulation techniques (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, noninvasive vagus nerve stimulation) share 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, 3
• Identify and reduce aggravating factors and triggers using a headache diary 2

Common Pitfalls to Avoid

Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead, transition to preventive therapy while optimizing acute treatment strategy. 1

• Do not restrict metoclopramide only to patients who are vomiting, as nausea itself is one of the most disabling symptoms and warrants treatment 1
• Ensure early administration of triptans while headache is still mild, as they are most effective when taken early in the attack 1, 2
• Do not assume failure of all triptans based on one triptan failure; try at least 2-3 different triptans before declaring triptan failure 1, 2
• Rule out medication-overuse headache before escalating therapy in patients with increasing headache frequency 1