What are the recommended anti-seizure medications for patients with brain metastasis?

Anti-Seizure Medication for Brain Metastasis

Primary Prophylaxis: Not Recommended

Prophylactic anti-seizure medications should NOT be prescribed for patients with brain metastases who have never had a seizure. 1

• Multiple high-quality guidelines from the Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consistently demonstrate that anticonvulsant prophylaxis is unlikely to be effective in increasing seizure-free survival or reducing first seizures at 6 months from diagnosis 1
• This recommendation holds even for patients undergoing neurosurgical procedures (craniotomy or biopsy), where perioperative prophylaxis is possibly not effective in reducing seizures during the first 14 days following surgery 1
• The EANO-ESMO guidelines explicitly state: "Primary anticonvulsant prophylaxis is not indicated in brain tumor patients" (Level I, Grade D evidence) 1
• Approximately 10-20% of patients with brain metastases present with seizures at diagnosis, and another 10-11% develop seizures later, but prophylaxis does not prevent these events 1

When to Treat: After a Verified Seizure

Initiate anti-seizure medication only after a patient with brain metastases has experienced a documented seizure. 1, 2

• Secondary prophylaxis (treatment after a first seizure) is strongly recommended to prevent recurrence 1
• Worsening of a pre-existing seizure disorder often heralds tumor progression and should trigger repeat MRI 1

First-Line Agent: Levetiracetam

Levetiracetam is the preferred first-line anti-seizure medication for patients with brain metastases who have had a seizure. 1

Why Levetiracetam is Preferred:

• Superior tolerability profile: Levetiracetam has fewer adverse drug reactions and higher retention rates compared to older agents like phenytoin and carbamazepine 1
• No drug interactions: Unlike enzyme-inducing AEDs, levetiracetam does not induce cytochrome P450 enzymes, avoiding interactions with chemotherapy agents, steroids, and targeted therapies 1, 3, 4
• Equivalent efficacy: Prevention of early postoperative seizures is comparable to first-generation AEDs but with significantly fewer side effects 1
• Practical advantages: Available in both oral and intravenous formulations with equivalent bioavailability, allowing use in emergency situations 4
• Recommended dosing: 1000-2000 mg/day divided twice daily 5

Important Caveat:

• Psychiatric side effects: Levetiracetam can cause mood disturbances, irritability, and behavioral changes in some patients 1, 2
• Contraindication: Avoid levetiracetam in patients with pre-existing psychiatric comorbidities 2

Alternative First-Line Options

If levetiracetam is not tolerated or contraindicated, lamotrigine is the next preferred option. 1

• Lamotrigine has good anti-seizure activity and overall good tolerability 1
• Major limitation: Requires several weeks of gradual titration to reach therapeutic levels, making it unsuitable for acute seizure management 1

Second-Line and Add-On Options

For patients who fail levetiracetam monotherapy or require additional seizure control, consider these agents: 2, 6

• Lacosamide: May assume a larger role as add-on treatment for refractory seizures 1, 2
• Valproic acid: Still has efficacy and overall good tolerability in some centers 1
  • Critical warning: Must NOT be used in females of childbearing potential 1
  • Hematologic toxicity: Associated with significantly higher risk of grade 3-4 hematologic toxicities when combined with temozolomide chemotherapy 1
  • Other complications: Risk of thrombocytopenia and hepatotoxicity 1
• Briviracetam: Appropriate alternative option 2
• Perampanel: Can be considered for add-on therapy 2

Medications to Avoid

Enzyme-inducing anti-seizure medications should be avoided in patients with brain metastases. 1

Specifically Avoid:

• Phenytoin 1, 7
• Carbamazepine 1, 7
• Phenobarbital 1

Reasons for Avoidance:

• These agents are potent inducers of hepatic CYP3A4 and other cytochrome P450 enzymes 7, 3
• They significantly reduce plasma concentrations of chemotherapy agents (including temozolomide, imatinib, and targeted therapies), potentially compromising anti-tumor activity 7, 3
• They interact with corticosteroids, reducing their effectiveness 1
• They have unfavorable side-effect profiles including cognitive impairment, dermatologic reactions, and require serum level monitoring 1, 7

Duration of Therapy

Continue anti-seizure medication until local tumor control has been achieved. 1

• For patients undergoing surgery with near-total resection, anticonvulsants can be tapered and discontinued within weeks after surgery if no recurrent bleeding occurs 5
• For patients with partial resection or non-surgical management, continue treatment until local control is established 5
• If anticonvulsants were started perioperatively in seizure-free patients, strongly consider discontinuation after the perioperative period 1

Special Monitoring Considerations

• New or worsening seizures: Should trigger repeat neuroimaging to evaluate for tumor progression 1
• Impaired consciousness: Consider continuous EEG monitoring for at least 24 hours to detect subclinical seizures 5
• Serum drug levels: Generally not necessary for levetiracetam, but may be useful for valproic acid if used 8

High-Risk Populations

Melanoma and lung cancer metastases carry the highest seizure risk. 1, 9

• Despite higher risk, prophylaxis is still not recommended even in these populations 1
• Insufficient evidence exists to support prophylactic AEDs even in metastatic melanoma to the brain 1