Sodium channel blockade, GABA enhancement or calcium channel blockade
Mnemonic
Group by target:
- Sodium channel blockers - carbamazepine, phenytoin, lamotrigine, oxcarbazepine. Good for focal seizures; carbamazepine and phenytoin worsen absence and myoclonic seizures
- Calcium channel (T type) - ethosuximide, the drug for absence seizures
- GABA enhancers - benzodiazepines, sodium valproate (multiple mechanisms), phenobarbitone, vigabatrin, tiagabine
- Glutamate and SV2A - levetiracetam (SV2A), topiramate, perampanel
“Ethosuximide for absence, valproate for everything, carbamazepine for focal.”
Sodium valproate is contraindicated in women and girls of childbearing potential unless the pregnancy prevention programme conditions are met, because of neural tube defects and neurodevelopmental harm.
Lamotrigine and levetiracetam are preferred in pregnancy, and lamotrigine carries the risk of Stevens-Johnson syndrome if titrated too fast, particularly with valproate, which inhibits its metabolism.
Phenytoin has zero order kinetics, so small dose increases cause large level rises.
Expansion
| Drug | Mechanism | Key adverse effects |
|---|---|---|
| Sodium valproate | Multiple: sodium channels, GABA | Teratogenic (neural tube, neurodevelopmental), weight gain, tremor, hepatotoxicity, hair loss, enzyme inhibitor |
| Carbamazepine | Sodium channel | Enzyme inducer, hyponatraemia (SIADH), rash including Stevens-Johnson (HLA-B*1502), agranulocytosis, diplopia |
| Lamotrigine | Sodium channel | Rash including Stevens-Johnson; titrate slowly, especially with valproate |
| Levetiracetam | SV2A binding | Behavioural and mood change; renally cleared; few interactions |
| Phenytoin | Sodium channel | Zero order kinetics, gum hypertrophy, hirsutism, ataxia, cerebellar atrophy, enzyme inducer |
| Ethosuximide | T-type calcium | For absence seizures |
| Topiramate | Multiple | Weight loss, renal stones, cognitive slowing, teratogenic |
Seizure type guides choice: broadly, sodium valproate or lamotrigine for generalised seizures, lamotrigine or levetiracetam for focal seizures, and ethosuximide for absence.
Valproate must not be used in women of childbearing potential unless there is no alternative and pregnancy prevention conditions are met. Carbamazepine can worsen absence and myoclonic seizures.