What medications are recommended for a patient with migraine headaches, considering their medical history and potential cardiovascular disease?

Migraine Headache Medications

First-Line Treatment for Mild to Moderate Migraine

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg, taken as early as possible when pain is still mild. 1, 2

• NSAIDs with the strongest evidence include aspirin, ibuprofen, naproxen sodium, and diclofenac potassium 1, 3
• Combination therapy with acetaminophen, aspirin, and caffeine (e.g., Excedrin Migraine) is also highly effective for mild to moderate attacks 1, 3
• Take medication at the earliest sign of headache for maximum effectiveness 1, 2

First-Line Treatment for Moderate to Severe Migraine

For moderate to severe migraine, use combination therapy with a triptan PLUS an NSAID, which is superior to either agent alone and represents the strongest current recommendation. 1, 2

• This combination provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 2
• Oral triptans with strong evidence include sumatriptan 50-100 mg, rizatriptan, naratriptan, and zolmitriptan 1, 3
• The combination of sumatriptan 50-100 mg PLUS naproxen sodium 500 mg has the highest level of evidence 1

Route Selection Based on Symptoms

• Oral route: Preferred for most patients without significant nausea 1, 2
• Subcutaneous sumatriptan 6 mg: Most effective and rapidly acting option (onset within 15 minutes), achieving pain relief in 70-82% of patients; use for severe attacks with rapid progression or significant vomiting 1
• Intranasal triptans: Useful alternative when nausea/vomiting is present 1

Critical Cardiovascular Considerations

Before prescribing triptans to patients with cardiovascular risk factors (increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), perform a cardiovascular evaluation. 4

• Triptans are absolutely contraindicated in patients with: 4, 5

  • Ischemic heart disease or history of myocardial infarction
  • Coronary artery vasospasm (Prinzmetal's angina)
  • Uncontrolled hypertension
  • History of stroke or TIA
  • Peripheral vascular disease
  • Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders

• For triptan-naive patients with multiple cardiovascular risk factors but negative cardiovascular evaluation, consider administering the first dose in a medically supervised setting with ECG monitoring 4

Alternative Options When Triptans Are Contraindicated

For patients with cardiovascular disease or contraindications to triptans, use CGRP antagonists (gepants) as the primary alternative: ubrogepant 50-100 mg or rimegepant. 1

• Gepants have no vasoconstriction, making them safe for patients with cardiovascular disease 1
• Lasmiditan (Reyvow) 50-200 mg is a second-line alternative without vasoconstrictor activity, but patients must not drive for at least 8 hours after taking it due to CNS effects 1
• Dihydroergotamine (DHE) has good efficacy evidence but shares similar cardiovascular contraindications as triptans 1

IV Treatment for Severe Migraine in Emergency/Urgent Care Settings

The optimal IV "headache cocktail" consists of metoclopramide 10 mg IV PLUS ketorolac 30 mg IV. 1

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, beyond just treating nausea 1
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 1
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy 1
• Use caution with ketorolac in patients with renal impairment, history of GI bleeding, or heart disease 1

Medications to Absolutely Avoid

Do not use opioids or butalbital-containing compounds for acute migraine treatment. 1, 2

• Opioids lead to dependency, rebound headaches, and eventual loss of efficacy 1, 2, 6
• They have questionable efficacy for migraine and increase risk of progression to chronic migraine 1, 6
• Reserve opioids only for cases where all other medications are contraindicated and abuse risk has been addressed 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit ALL acute migraine medications to a maximum of 2 days per week (10 days per month) to prevent medication-overuse headache. 1, 2

• NSAIDs cause medication-overuse headache if used ≥15 days/month 1, 2
• Triptans cause medication-overuse headache if used ≥10 days/month 1, 2, 4
• If needing acute treatment more than twice weekly, immediately initiate preventive therapy 1, 2

When to Initiate Preventive Therapy

Start preventive therapy for patients experiencing ≥2 migraine attacks per month with disability lasting ≥3 days, or using acute medications more than twice weekly. 7

First-Line Preventive Medications

• Propranolol 80-240 mg/day or timolol 20-30 mg/day (beta-blockers without intrinsic sympathomimetic activity) 7
• Topiramate 50-100 mg/day (particularly useful for patients with obesity due to weight loss effects) 7
• Candesartan (particularly useful for patients with comorbid hypertension) 7

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day (optimal for patients with comorbid depression, anxiety, or mixed migraine/tension-type headache) 7
• Flunarizine 5-10 mg once daily at night (effective second-line agent where available, but avoid in elderly due to risk of extrapyramidal symptoms and depression) 7
• Sodium valproate/divalproex sodium are strictly contraindicated in women of childbearing potential due to teratogenic effects 7

Third-Line: CGRP Monoclonal Antibodies

• Consider erenumab, fremanezumab, or galcanezumab after failure of 2-3 oral preventive medications 7
• Administered monthly via subcutaneous injection with efficacy assessment requiring 3-6 months 7
• Significantly more expensive ($5,000-$6,000 annually) than oral agents 7

Implementation Strategy

• Start low, titrate slowly with preventive medications until clinical benefits are achieved or side effects limit further increases 7
• Allow an adequate trial period of 2-3 months for oral preventives before declaring failure 7
• For CGRP monoclonal antibodies, assess efficacy only after 3-6 months 7
• Consider tapering preventive therapy after 6-12 months of successful treatment to determine if it can be discontinued 7

Special Populations

Pregnancy and Lactation

• Acetaminophen is the safest option during pregnancy 2
• Sumatriptan may be an option for selected pregnant patients and is compatible with breastfeeding 2
• Discuss adverse effects of all pharmacologic treatments with patients of childbearing potential before initiating therapy 2
• Valproate is strictly contraindicated due to teratogenic risk 7

Common Pitfalls to Avoid

• Inadequate dosing before declaring treatment failure - ensure full therapeutic doses are used 2
• Delayed administration - medication must be taken early in the attack while pain is still mild 1, 2
• Not combining triptan with NSAID for moderate to severe attacks - combination is superior to monotherapy 1, 2
• Allowing escalation of acute medication frequency - this creates medication-overuse headache; transition to preventive therapy instead 1
• Failing to screen for cardiovascular risk factors before prescribing triptans 4
• Starting preventive medications at too high a dose - leads to poor tolerability and discontinuation 7
• Inadequate duration of preventive trial (less than 2-3 months) before switching medications 7