What are the criteria for the prophylactic use of anti-epileptic drugs (AEDs)?

Criteria for Prophylactic Use of Anti-Epileptic Drugs

Prophylactic anti-epileptic drugs (AEDs) should NOT be routinely prescribed in patients with brain tumors who have not experienced seizures. 1

Brain Tumors

Primary Recommendation

• In patients with newly diagnosed brain tumors who have never had a seizure, clinicians should NOT prescribe AEDs prophylactically (Level A evidence) 1
• This recommendation applies regardless of tumor characteristics such as:
  • Location
  • Histology (primary vs. metastatic)
  • Grade
  • Molecular/imaging features 1

Perioperative Setting

• There is insufficient evidence to recommend prophylactic AEDs for patients undergoing neurosurgical procedures for brain tumors (Level C evidence) 1
• If AEDs are started for surgery, they should be discontinued after the first postoperative week 1

AED Selection (if needed for seizure treatment)

• If AEDs are required for patients who have experienced seizures:
  • Consider levetiracetam over older AEDs to reduce side effects (Level C evidence) 1
  • Avoid enzyme-inducing AEDs (EIAEDs) such as phenytoin, phenobarbital, and carbamazepine due to potential interactions with chemotherapeutic agents 1
  • Prefer non-enzyme-inducing AEDs (NEIAEDs) such as levetiracetam, topiramate, and valproic acid 1

Other Neurological Conditions

Traumatic Brain Injury

• Evidence for prophylactic AED use in TBI is modest 2
• While some observational studies suggest a protective effect, randomized controlled trials show inconsistent results 2

Stroke and Hemorrhage

• Prophylactic AEDs are not routinely recommended for ischemic stroke, hemorrhagic stroke, or subarachnoid hemorrhage 3, 4
• Prevention of early (provoked) seizures may be considered in specific high-risk situations, but prevention of delayed epilepsy is not supported by evidence 4

Rationale Against Routine Prophylaxis

Lack of Efficacy

• Meta-analyses show no significant reduction in seizure incidence with prophylactic AEDs in brain tumor patients (OR=0.939,95%CI=0.609-1.448) 5

Potential Harms

• Significant side effects of AEDs include:
  • Cognitive impairment
  • Neuropsychiatric disorders
  • Fatigue
  • Myelosuppression
  • Liver dysfunction
  • Dermatologic reactions
  • Drug interactions with chemotherapy 1

Considerations for AED Withdrawal

For patients already on AEDs who have been seizure-free:

• Consider tapering and discontinuing AEDs in patients who have been seizure-free for 24 consecutive months 6
• Factors favoring successful AED withdrawal include:
  • Normal neurological examination
  • Normal IQ
  • Normal EEG prior to withdrawal
  • Early response to initial treatment
  • Complete resolution of underlying cause 6

Common Pitfalls to Avoid

1. Automatic prophylaxis: Avoid automatically prescribing AEDs to all brain tumor patients despite lack of evidence for benefit
2. Prolonged perioperative prophylaxis: If started for surgery, AEDs should be discontinued after the first postoperative week
3. Using enzyme-inducing AEDs: These can significantly interact with chemotherapeutic agents
4. Overlooking quality of life: AED side effects can significantly impact patient quality of life
5. Failing to reassess: Patients on AEDs should be regularly evaluated for the possibility of discontinuation if seizure-free

Conclusion

The current evidence strongly recommends against routine prophylactic use of AEDs in patients with brain tumors who have not experienced seizures. The potential harms of AED therapy outweigh the unproven benefits in this population.