What is the recommended acute and preventive medication management for migraine, including considerations for cardiovascular disease, hypertension, and patients over 65?

Migraine Medication Management

For acute episodic migraine, start with combination therapy of a triptan plus an NSAID or acetaminophen as first-line treatment for moderate to severe attacks, and use NSAIDs or acetaminophen alone for mild attacks. 1

Acute Treatment Algorithm

Mild Episodic Migraine

• Use NSAIDs (aspirin, celecoxib, diclofenac, ibuprofen, or naproxen), acetaminophen, or their combination 1
• Ensure adequate dosing before escalating therapy 1

Moderate to Severe Episodic Migraine

First-line: Combination therapy of a triptan (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan) plus an NSAID or acetaminophen 1

Second-line (if inadequate response or intolerance to first-line):

• CGRP antagonists-gepants: rimegepant, ubrogepant, or zavegepant 1
• Ergot alkaloid: dihydroergotamine 1

Third-line (if all above fail):

• Lasmiditan (ditan class) 1

Special circumstances:

• For severe nausea/vomiting: Use nonoral triptan plus antiemetic 1
• Never use opioids or butalbital 1

Critical Timing Consideration

Begin treatment as soon as possible after migraine onset using combination therapy to maximize efficacy 1

Special Populations

Cardiovascular Disease and Hypertension

• Gepants are likely safe for acute therapy in cardiovascular disease 2, 3
• NSAIDs, ergotamines, and triptans are NOT recommended in cardiovascular disease 2, 4
• Lasmiditan has no cardiovascular safety concerns and can be used in those with cardiovascular disease 3
• For prevention: Beta-blockers, ACE inhibitors/ARBs, and verapamil provide dual cardiovascular and migraine benefits 2
• Use CGRP antagonists with caution in small vessel disease, as vasodilation may be compromised mid-ischemia 3
• Erenumab (CGRP mAb) has been associated with hypertension 3

Patients Over 65 Years

• Avoid triptans and dihydroergotamine due to coronary artery disease risk 5, 6
• For acute treatment: Use naproxen and hydroxyzine as oral rescue therapies 6
• For severe attacks in emergency settings: Intravenous magnesium, valproic acid, or metoclopramide 6
• Avoid tricyclic antidepressants (amitriptyline, doxepin) for prevention due to cognitive impairment, urinary retention, and cardiac arrhythmia risks 6
• Recommended preventive agents: Divalproex sodium, topiramate, metoprolol, or propranolol 6
• Frovatriptan requires no dose adjustments in mild to moderate renal or hepatic disease 2
• OnabotulinumtoxinA is likely safe in cardiac, renal, and hepatic impairment 2

Renal and Hepatic Disease

• Frovatriptan: No dose adjustment needed in kidney disease or mild-moderate liver disease 2
• Gepants: Safe in mild and moderate renal and hepatic disease for both acute and preventive use 2
• TCAs and valproic acid: No dose adjustments needed in renal disease 2
• OnabotulinumtoxinA: Likely safe in renal and hepatic impairment 2

Preventive Treatment

Consider preventive therapy when:

• Episodic migraine occurs frequently 1
• Acute treatment provides inadequate response 1
• Patient unable to tolerate acute treatment or has contraindications 1
• Patient uses acute treatment more often than recommended 1

Key preventive principles:

• Start at low dose and gradually titrate until desired outcomes achieved 1
• Allow 2-3 months for adequate trial before switching 1
• Adherence is crucial as improvement occurs gradually over weeks 1
• Cost should be a key factor given similar net benefits across recommended treatments 1

Alternative preventive options (if first-line not tolerated):

• ACE inhibitor: Lisinopril 1
• ARBs: Candesartan or telmisartan 1
• SSRI: Fluoxetine 1

Critical Safety Warnings

Medication Overuse Headache

Monitor for medication overuse headache, defined as headache occurring ≥15 days per month for ≥3 months due to overuse of acute medication 1

Thresholds vary by medication:

• NSAIDs: ≥15 days per month 1
• Triptans: ≥10 days per month 1

Pregnancy and Lactation

Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation with patients of childbearing potential 1

Essential Lifestyle Modifications

Counsel all patients on:

• Maintain adequate hydration 1
• Regular meal timing 1
• Sufficient and consistent sleep 1
• Regular moderate to intense aerobic exercise 1
• Stress management with relaxation techniques or mindfulness 1
• Weight loss for overweight/obese patients 1
• Identify and modify migraine triggers through detailed history 1

Use headache diary to determine treatment efficacy, identify analgesic overuse, and monitor migraine progression 1

Cost Considerations

Prescribe less costly recommended medications when possible 1

Annualized costs (wholesale acquisition cost):

• CGRP antagonists-gepants oral: $4,959-$5,994 1
• CGRP antagonists-gepants intranasal: $8,800 1
• Dihydroergotamine intranasal: $1,320 1
• Dihydroergotamine injectable: $4,042 1

Common Pitfalls

• Failing to ensure adequate dosing of NSAIDs/acetaminophen before adding triptans 1
• Not recognizing that patients may respond to different agents within the same drug class 1
• Using opioids or butalbital, which are explicitly contraindicated 1
• Prescribing triptans or ergotamines in patients with cardiovascular disease 2, 4, 6
• Not monitoring for medication overuse headache with different thresholds for different drug classes 1