Epilepsy II: Treatment and management

When to treat?

Most physicians would recommend treatment when a person has suffered two or more seizures within a 2-year period. The risk of recurrence after a first seizure varies according to the aetiology and seizure syndrome and may influence the decision on when to treat.

Principles of medical treatment

Which treatment to use depends on the epilepsy syndrome, seizure types and adverse effect profile. One drug should be used, where possible, and the dose titrated against response and adverse effects. Sixty per cent of patients will respond to first-line therapy, becoming seizure-free for at least 2 years. Monotherapy carries the lowest risk of adverse effects, which increase substantially with increasing numbers of drugs. For most drugs, the correct dose is the lowest effective dose that does not cause side effects. A drug should not be considered ineffective until it has been tried to the maximum dose that does not cause adverse effects, which varies between patients. For refractory cases, more than one drug may be required and some will remain refractory to all agents. Using more than three drugs concurrently should be avoided.

Some refractory cases, on re-evaluation, prove to have non-epileptic (psychogenic) seizures, also referred to as pseudoseizures (p. 116). In others, poor compliance contributes to poor control.

In refractory cases where these factors have been excluded, if there is evidence of focal seizure onset, surgery may be considered (see below).

Choice of medication

The major divisions into generalized and focal-onset epilepsies are important in the choice of drug (Fig. 1). Medications can broadly be divided into those useful in focal epilepsy, those with a broad spectrum of action and those for specific seizure types. Carbamazepine, lamotrigine and valproate are the commonest first-line drugs in the UK. The choice is also heavily influenced by the age of the patient because this affects their susceptibility to the side effects of different drugs. For example, focal-onset epilepsy in a young woman is often treated with carbamazepine or lamotrigine as first line because of its lower risk of teratogenicity, but sodium valproate is favoured in the elderly because of a lower risk of ataxia and falls. Lamotrigine is emerging as a broad-spectrum drug, well tolerated in many patient groups.

Measurement of drug levels in blood

This is of benefit in limited situations:

In judging drug dosage, blood levels are most useful for patients on phenytoin therapy. The saturation kinetics of this drug give it a particularly narrow therapeutic window. There is substantial variability between patients. There is some value in measuring drug levels in patients receiving carbamazepine or barbiturates but little benefit for other drugs apart from finding out whether the patient is taking them (e.g. unconscious patient).

Adverse effects

The adverse effects of antiepileptic drugs are common and major adverse effects are listed in Table 1. Sedation can occur with all drugs and is the most common complaint, especially with polytherapy. Another concern is teratogenicity. Women of childbearing age on antiepileptic medication should be counselled of the risk and their medication minimized prior to conception. Although not proven to be of benefit, folic acid supplements (5 mg daily) are generally prescribed to women of childbearing age taking antiepileptic drugs as it may help to prevent neural tube defects. The risk of major malformations for a woman taking anticonvulsants is about 4–9%, compared with about 1–2% in the general population. It is highest for those on valproate and on multiple drugs.

Table 1 Selected adverse effects of anticonvulsant drugs

Adverse effect	Drugs
Sedation	All drugs, especially phenobarbital and benzodiazepines Substantial individual variation

Diplopia and ataxia Phenobarbital, phenytoin, carbamazepine, lamotrigine Rash Carbamazepine, lamotrigine, phenytoin Gastrointestinal effects Carbamazepine, sodium valproate Weight gain Sodium valproate, vigabatrin, gabapentin, pregabalin, others infrequently Weight loss Topiramate, zonisamide Reversible hair loss Sodium valproate, vigabatrin Teratogenic effects