What is the recommended medication for a patient with migraines, considering their past medical history and potential risk for cardiovascular complications?

Migraine Medication: Evidence-Based Treatment Algorithm

First-Line Acute Treatment for Mild to Moderate Migraine

Start with NSAIDs as first-line therapy for mild to moderate migraine attacks, specifically ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg, taken at migraine onset when pain is still mild. 1

• NSAIDs demonstrate strong efficacy with favorable tolerability profiles and minimal risk of rebound headache 1
• Naproxen provides pain-free response at 2 hours with a number needed to treat (NNT) of 11, and can be repeated every 2-6 hours with a maximum of 1.5 g per day 1
• Critical frequency limitation: Restrict NSAID use to no more than 2 days per week to prevent medication-overuse headache 1

Adjunctive Antiemetic Therapy

• Add metoclopramide 10 mg or prochlorperazine 25 mg orally 20-30 minutes before the NSAID to provide synergistic analgesia and improve outcomes compared to NSAIDs alone 1
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic effects 1

First-Line Treatment for Moderate to Severe Migraine

For moderate to severe attacks or when NSAIDs fail after 2-3 episodes, escalate to combination therapy with a triptan PLUS an NSAID, as this combination is superior to either agent alone. 1

Optimal Triptan Selection Based on Clinical Scenario

Oral triptans for standard moderate-severe attacks:

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg provides sustained pain relief in 130 more patients per 1000 at 48 hours compared to either agent alone 1
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan 1, 2
• Eletriptan 40 mg or zolmitriptan 2.5-5 mg are more effective with fewer adverse reactions than sumatriptan 1, 3
• Naratriptan has the longest half-life, which may decrease recurrence headaches 1

Non-oral routes when significant nausea/vomiting is present:

• Subcutaneous sumatriptan 6 mg provides the highest efficacy with 59% achieving complete pain relief by 2 hours and onset within 15 minutes 1, 4
• Intranasal sumatriptan 5-20 mg or zolmitriptan provides significant pain-free rates as early as 15 minutes post-administration 1, 5
• Rizatriptan orally disintegrating wafer offers non-oral administration without injection 1, 2

Critical Triptan Prescribing Considerations

Absolute contraindications to triptans: 6, 3

• Ischemic heart disease, previous myocardial infarction, or significant cardiovascular disease
• Uncontrolled hypertension
• Hemiplegic or basilar migraine
• Peripheral vascular disease
• History of stroke or transient ischemic attacks
• Within 24 hours of ergotamine-containing medications or other triptans

For patients with cardiovascular risk factors (hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of heart disease), a cardiac evaluation must be performed before prescribing triptans, and the first dose should be administered in a medical setting. 1, 6

Emergency Department/Urgent Care IV Treatment

The optimal IV headache cocktail consists of metoclopramide 10 mg IV PLUS ketorolac 30 mg IV, providing rapid pain relief while minimizing side effects and rebound headache risk. 1

• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 1
• Metoclopramide provides independent analgesic benefit through central dopamine receptor antagonism beyond its antiemetic properties 1
• Prochlorperazine 10 mg IV is equally effective as metoclopramide with a more favorable side effect profile (21% adverse events vs 50% with chlorpromazine) 1

Alternative IV Options

• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy 1
• Avoid opioids (hydromorphone, meperidine) or butalbital-containing compounds as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1

When Triptans Fail: Escalation Algorithm

If one triptan fails after 2-3 headache episodes, try a different triptan first, as failure of one does not predict failure of others. 1

Newer CGRP Antagonists (Gepants)

If all triptans fail after adequate trials, escalate to CGRP antagonists: ubrogepant 50-100 mg or rimegepant as the primary oral alternative, as they have no vasoconstriction and are safe for patients with cardiovascular disease. 1

Ditans

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

Preventive Therapy Indications

Initiate preventive therapy immediately if any of the following criteria are met: 7

• Two or more migraine attacks per month producing disability lasting 3 or more days
• Using acute medications more than 2 days per week (to prevent medication-overuse headache)
• Contraindication to or failure of acute treatments
• Uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction)

First-Line Preventive Medications

Beta-blockers without intrinsic sympathomimetic activity: 7

• Propranolol 80-240 mg/day (FDA approved with strong evidence)
• Timolol 20-30 mg/day
• Alternative beta-blockers: atenolol, bisoprolol, or metoprolol

Other first-line options: 7

• Topiramate 50-100 mg/day (particularly useful for patients with obesity due to associated weight loss)
• Candesartan (particularly useful for patients with comorbid hypertension)

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day (optimal for patients with comorbid depression, anxiety, or mixed migraine and tension-type headache) 7
• Valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are strictly contraindicated in women of childbearing potential due to teratogenic effects 7
• Flunarizine 5-10 mg once daily at night (effective second-line agent with efficacy comparable to propranolol and topiramate) 7

Third-Line: CGRP Monoclonal Antibodies

Consider erenumab, fremanezumab, or galcanezumab (monthly subcutaneous injection) when 2-3 oral preventive medications have failed, with efficacy assessment requiring 3-6 months. 7

Implementation Strategy

• Start with low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 7
• Allow adequate trial period of 2-3 months for oral agents before determining efficacy 7
• Track attack frequency, severity, duration, disability, treatment response, and adverse effects using headache diaries 7

Critical Pitfalls to Avoid

Medication-overuse headache (MOH) is the most common pitfall, occurring when acute medications are used ≥10 days/month for triptans or ≥15 days/month for NSAIDs, leading to daily headaches and loss of treatment responsiveness. 1

• Never allow patients to increase frequency of acute medication use in response to treatment failure—this creates a vicious cycle of MOH 1
• Instead, transition to preventive therapy while optimizing acute treatment strategy 1
• Rule out MOH before escalating therapy or declaring treatment failure 1

Do not use triptans and ergotamine-containing medications (Cafergot) within 24 hours of each other due to additive vasoconstrictive effects. 1, 6

Avoid establishing patterns of opioid use for headache management, as this leads to dependency, rebound headaches, and eventual loss of efficacy. 1