Epilepsy Treatment

The majority of patients respond to drug therapy (anticonvulsants). In intractable cases surgery may be necessary. Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). Poly therapy is to be avoided especially as drug interactions occur between major anticonvulsants.

Treatment is aimed at rendering the patient 'fit free', though not always achieved. If the patient goes three years without an attack, withdrawal of therapy should be considered. Withdrawal should be carried out only if the patient is satisfied that a further fit would not ruin employment etc. (e.g. car driver). The risk of teratogenicity is well known (6%) especially with phenytoin, but withdrawing drug therapy in pregnancy is perhaps more risky than continuation. All anticonvulsants probably have some risk of producing fetal abnormalities, though these are usually mild. Sodium valproate has been incriminated in neural tube defects - spina bifida.

The introduction of assay of blood anticonvulsant levels has led to:

1. Identification of non-compliers - a common problem at epilepsy clinics.

2. Tailoring of drug dose to patient's requirements.

3. The realisation of failure with therapeutic levels of one anticonvulsant and thus the logical change to another.

The commonest anticonvulsants in present clinical use are: Carbamazepine Sodium valproate Clonazepam Ethosuximide Phenobarbitone Primidone Phenytoin

Sodium valproate is the first-line drug in the treatment of the generalised epilepsies in adults. In childhood use ethosuximide. Carbamazepine is the first-line drug in the treatment of partial seizures and partial seizures evolving to tonic/clonic seizures.

Sodium valproate

Phenobarbitone

Phenytoin

Carbamazepine

Mode of action

Inhibitor of GABA transaminase and glutamate decarboxylase

Opens postsynaptic CI" ion channels decreasing Na+ & Ca2+ influx

Blocks voltage dependent Na+ channels in neuronal cell membrane

Blocks voltage dependent Na+ channels in neuronal cell membrane

Protein bound Short variable half-life

Liver or excreted in urine unchanged Long half-life (60 hours)

Liver

Can saturate enzyme systems Long half-life

Liver

Enzyme inducer Short half-life (10 hours)

Dose (ADULT)

2-3 x daily 600 mg to 3 g total daily dose

Can be given as single dose, e.g. 90 mg at night

Can be given as single dose e.g. 150-400 mg at night

2-3 x daily 600 mg to 1.2 g total daily dose

Side effects

Gastrointestinal upset Thrombocytopenia Drug-induced hepatitis Hair loss Tremor/chorea

Sedation. Depression Behavioural disturbance in children Skin rashes Withdrawal seizures

Gum hypertrophy Acne. Coarsening of facial characteristics At toxic levels

- nystagmus

- ataxia, diplopia

- neuropathy

Gastrointestinal upset Ataxia Skin rash Agranulocytosis Antidiuretic effect

New anticonvulsants are available, sometimes used in conjunction with conventional drugs - Vigabatrin (inhibits GABA transaminase), Gabapentin (GABA analogue), Lamotrigine (inhibits glutamate release) and Flunarizine (Ca2+ channel blocker).

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