Should a patient with a new diagnosis of glioblastoma be given prophylactic anti-seizure (antiepileptic) medicine?

Prophylactic Antiseizure Medication in Newly Diagnosed Glioblastoma

Patients with newly diagnosed glioblastoma who have not experienced seizures should NOT be prescribed prophylactic antiseizure medications. 1

Evidence-Based Recommendation

The Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) practice guidelines provide a Level A recommendation against prophylactic antiseizure drugs (ASDs) in patients with newly diagnosed brain tumors who have not had seizures 1. This recommendation is based on multiple studies showing lack of efficacy for seizure prevention while exposing patients to potential adverse effects.

Key Evidence Supporting This Recommendation:

• Multiple studies demonstrate no benefit of prophylactic ASDs in preventing first seizures in brain tumor patients 1, 2
• Meta-analyses confirm lack of benefit at both 1 week and 6 months of follow-up 3
• The risk of adverse events is significantly higher for patients on prophylactic ASDs (NNH = 3) 2

Perioperative Considerations

For patients undergoing neurosurgical procedures (craniotomy or biopsy):

• There is insufficient evidence to recommend routine perioperative ASD prophylaxis (Level C) 1
• Studies show prophylactic ASDs do not prolong time to seizure occurrence 1
• If ASDs are started for perioperative prophylaxis, they should be discontinued after the perioperative period 4

Tumor Characteristics and Seizure Risk

• Current data do not support using tumor location, histology, grade, molecular pathology, or imaging characteristics to guide prophylactic ASD use (Level U) 1
• Even for glioblastoma specifically, there is no evidence supporting prophylactic ASD use 5

Management When Seizures Occur

If a patient with glioblastoma develops seizures:

• Initiate ASD treatment promptly
• Consider levetiracetam as first-line therapy due to:
  • Better side effect profile compared to older ASDs (Level C) 1
  • No significant drug interactions with chemotherapy agents 1
  • Possible survival benefit in high-grade gliomas (though this requires further study) 6

Potential Pitfalls and Caveats

1. Widespread inappropriate practice: Despite clear guidelines, prophylactic ASD use remains pervasive and often prolonged in clinical practice 7

2. Medication interactions: Enzyme-inducing ASDs (phenytoin, carbamazepine, phenobarbital) can:

   • Reduce effectiveness of chemotherapy and steroids
   • Increase risk of adverse effects (adjusted OR: 3.32) 7

3. Adverse effects: Approximately 20% of patients experience ASD-related adverse effects, including:

   • Idiosyncratic cutaneous reactions
   • Hepatotoxicity
   • Cognitive impairment
   • Myelosuppression 1, 7

4. False sense of security: Prophylactic ASDs may create a false sense of security, as most seizures in brain tumor patients occur in a delayed fashion rather than immediately post-diagnosis 7

Conclusion

The evidence clearly demonstrates that prophylactic ASDs should not be routinely prescribed for patients with newly diagnosed glioblastoma who have not experienced seizures. This approach avoids unnecessary medication side effects and drug interactions while not increasing seizure risk. If seizures occur, prompt treatment with a non-enzyme-inducing ASD like levetiracetam is recommended.