Phenytoin and Absence Seizures
Phenytoin is known to worsen absence seizures and should be avoided in patients with primary generalized epilepsies characterized by absence, myoclonic, or atonic seizures.
Phenytoin's Seizure-Type Specificity
Effective Seizure Types
- Phenytoin is effective for generalized tonic-clonic seizures and partial seizures (simple partial, complex partial, and secondarily generalized seizures) 1, 2, 3
- The drug works by modulating sustained repetitive neuronal firing through voltage-gated sodium channel blockade 2
Contraindicated Seizure Types: Absence and Other Primary Generalized Seizures
- Phenytoin can precipitate or exacerbate absence seizures, atonic seizures, and myoclonic seizures in patients with generalized epilepsies characterized by diffuse, bilaterally synchronous spike-and-wave EEG activity 4
- This paradoxical worsening represents a distinct adverse primary action of the drug in specific seizure types, not simply a manifestation of drug intoxication 4
- The mechanism involves phenytoin's inability to suppress—and potential to aggravate—the generalized spike-wave discharges that characterize absence epilepsy 4
Clinical Implications and Common Pitfalls
Critical Diagnostic Requirement
- Seizure-worsening with phenytoin often results from incorrect diagnosis of seizure type or syndromic form 4
- Before prescribing phenytoin, clinicians must distinguish between partial-onset seizures (where phenytoin is appropriate) and primary generalized epilepsies (where it is contraindicated) 4
Additional Safety Concerns
- Phenytoin carries significant risks beyond seizure exacerbation, including excess morbidity and mortality when used for seizure prophylaxis in certain populations 5
- The drug causes cognitive impairment and cerebellar syndrome (phenytoin encephalopathy), particularly problematic in patients with intellectual disability 2
- Long-term use is not recommended for patients with marked cognitive impairment or cerebellar disease 2