What is the best approach to manage a patient with a history of migraines and epilepsy?

Managing Patients with Both Migraine and Epilepsy

For patients with comorbid migraine and epilepsy, valproate (500-1,000 mg daily) or topiramate (100-200 mg daily) should be the first-line preventive therapy, as these antiepileptic drugs effectively treat both conditions simultaneously while avoiding polypharmacy and drug interactions. 1, 2

Recognize the Bidirectional Relationship

• Epilepsy and migraine share common pathophysiological mechanisms, including neuronal hyperexcitability, ion channel dysfunction, and elevated extracellular glutamate levels that can trigger both cortical spreading depression (migraine aura) and seizures. 3, 4

• The comorbidity is more common than chance alone would predict: patients with epilepsy have higher rates of migraine than the general population, and vice versa. 5, 3, 6

• Migraine with aura increases the risk of developing epilepsy, particularly in patients with catamenial patterns. 6

• Direct migraine-triggered seizures (migralepsy) occur in approximately 1.7% of epilepsy patients, where seizures begin during or shortly after migraine aura and precede the headache phase. 2, 6

Select Preventive Therapy That Treats Both Conditions

First-Line Options

• Valproate (500-1,000 mg daily) is a first-line preventive agent for migraine that simultaneously provides seizure control. 2

• Topiramate (100-200 mg daily) is equally effective as first-line therapy for both migraine prevention and epilepsy management. 1, 2

• Choose between these based on patient-specific factors: topiramate is preferred in patients with obesity due to weight loss effects, while valproate should be avoided in women of childbearing potential due to teratogenicity risk. 1, 7

Critical Safety Considerations for Valproate

• Valproate carries a black box warning for hepatotoxicity, teratogenicity, and pancreatitis. 7

• Valproate is absolutely contraindicated in women of childbearing potential when treating migraine (a spontaneously reversible condition not associated with permanent injury or death), as it produces neural tube defects including spina bifida. 7

• Monitor liver function tests prior to therapy and frequently during the first six months in all patients on valproate. 7

• Warn patients about symptoms of pancreatitis (abdominal pain, nausea, vomiting, anorexia) and hepatotoxicity (malaise, weakness, lethargy, facial edema, loss of seizure control). 7

Medications to Avoid

• Older antiepileptic drugs (phenytoin, carbamazepine, phenobarbital) have no role in migraine prevention and should not be used when both conditions require treatment. 2

• Beta-blockers and amitriptyline lack robust evidence for chronic migraine in the context of epilepsy, though they may be considered if other options fail. 1

Manage Acute Migraine Attacks Carefully

• Limit acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache, which is the most common secondary cause of worsening migraines in this population. 1, 8, 9

• For mild-to-moderate attacks, start with acetaminophen 1000 mg as it has no seizure-provoking effects and minimal drug interactions with antiepileptic drugs. 9

• Add metoclopramide 10 mg orally 20-30 minutes before acetaminophen to enhance absorption and provide antiemetic effects. 9

• Escalate to triptans (sumatriptan 50-100 mg or rizatriptan) for inadequate response, as these are safe in epilepsy and do not lower seizure threshold. 9, 5

• Choose non-oral routes (intranasal or subcutaneous sumatriptan) if significant nausea or vomiting is present. 9

• Avoid ergotamine and opiates, as frequent use causes medication-overuse headaches and ergots are contraindicated in migraine with aura due to stroke risk. 1

Address Comorbid Conditions That Worsen Both Disorders

• Screen for and treat anxiety and depression, which occur at higher rates in patients with both migraine and epilepsy and significantly worsen quality of life. 1, 3

• Evaluate for medication-overuse headache by asking about frequency of acute medication use; if present, withdraw the overused medication abruptly (except opioids). 1

• Screen for obstructive sleep apnea (snoring, witnessed apneas, daytime somnolence), as this is a modifiable risk factor that worsens both migraine frequency and seizure control. 8

• Monitor for obesity and encourage weight loss, as this is a risk factor for transformation to chronic migraine. 1

Implement Non-Pharmacological Therapies

• Offer cognitive-behavioral therapy and biofeedback to all patients, as these have demonstrated efficacy for migraine prevention and are as effective as topiramate in randomized trials. 1

• Encourage regular exercise (40 minutes three times weekly), which has proven effectiveness for migraine prevention. 1

• Educate patients to maintain a headache diary to track triggers, medication use, and response to therapy. 1

Recognize When to Refer to Specialist Care

• Refer patients with chronic migraine (≥15 headache days per month for ≥3 months) to a headache specialist or neurologist. 1

• Refer patients with drug-resistant epilepsy or those requiring polytherapy, as the combination increases complexity and drug interaction risk. 5

• Refer patients with suspected migralepsy (seizures triggered by migraine aura) who may benefit from combined antimigraine and antiepileptic therapy optimization. 6

Monitor for Drug Interactions

• Valproate clearance is doubled by enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, phenobarbital), requiring dose adjustments and monitoring of drug levels. 7

• Aspirin increases valproate free fraction 4-fold and inhibits its metabolism; avoid concurrent use or monitor closely. 7

• Topiramate and valproate do not have significant interactions with triptans, making acute migraine treatment straightforward. 5

Common Pitfalls to Avoid

• Do not prescribe valproate to women of childbearing potential for migraine prevention, even if they have epilepsy, without extensive counseling about teratogenicity and contraception. 7

• Do not overlook medication-overuse headache as the cause of worsening migraines; this is more common than progression of primary disease. 1, 8

• Do not use multiple preventive medications simultaneously when a single agent (valproate or topiramate) can treat both conditions. 1, 5

• Do not ignore psychiatric comorbidities, as untreated anxiety and depression worsen outcomes for both migraine and epilepsy. 1, 3