Laboratory Testing for a Patient on Depakote and Topiramate Who Just Had a Seizure
For a patient already on antiepileptic drugs who experiences a breakthrough seizure, you should immediately check serum valproate level, complete blood count (CBC), comprehensive metabolic panel (CMP) including sodium and glucose, and serum ammonia level.
Essential Labs for Breakthrough Seizure on AEDs
Antiepileptic Drug Levels
- Check serum valproate level immediately to assess whether the patient has subtherapeutic levels (therapeutic range 50-100 μg/mL), which is the most common reversible cause of breakthrough seizures in patients on valproate 1
- Subtherapeutic valproate levels require immediate dose adjustment to prevent seizure recurrence and associated morbidity 2
- Note that topiramate levels are not routinely monitored as there is no established therapeutic range 3
Metabolic Panel
- Serum glucose and sodium are Level B recommendations for any seizure patient, as hypoglycemia and hyponatremia are the most frequent metabolic abnormalities causing seizures 4
- These abnormalities are usually predicted by history and physical examination, but unsuspected cases occur in 1-2% of patients 4
- Serum ammonia level is critical in patients on valproate plus topiramate due to the risk of hyperammonemic encephalopathy 5, 6
Complete Blood Count
- CBC with platelet count is essential because thrombocytopenia risk increases significantly at valproate levels above 110 μg/mL in females and 135 μg/mL in males 1
- This is a dose-related adverse effect that requires monitoring 1
Liver Function Tests
- Hepatic transaminases (AST/ALT) should be checked as valproate can cause hepatotoxicity, though hyperammonemic encephalopathy can occur with normal liver function 6
Critical Drug Interaction Consideration
The combination of topiramate and valproate significantly increases the risk of hyperammonemic encephalopathy, even with therapeutic valproate levels and normal liver function 5, 6. This syndrome presents with:
- Excessive sleepiness or somnolence
- Aggravation of seizures (which may explain the breakthrough seizure)
- Ammonia levels 1.5-2 times normal
- Normal or therapeutic valproate levels 5
This condition is reversible with cessation of either valproate or topiramate 5, 6.
Additional Considerations
Pregnancy Testing
- Obtain pregnancy test if patient is a woman of childbearing age (Level B recommendation), as this affects testing, disposition, and antiepileptic drug therapy decisions 4
Serum Bicarbonate
- Baseline and periodic serum bicarbonate should be measured during topiramate treatment, as topiramate is a carbonic anhydrase inhibitor that can cause metabolic acidosis 3
Common Pitfall to Avoid
Do not assume the seizure is simply due to medication non-compliance without checking drug levels and ammonia. The topiramate-valproate combination can cause hyperammonemic encephalopathy with worsening seizures even when patients are compliant and valproate levels are therapeutic 5, 6. Missing this diagnosis can lead to continued seizures and neurological deterioration when the solution is to discontinue one of the medications rather than increase doses.