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Enzyme-inducing AEDs, however, decrease the half-life of tiagabine and people taking such
drugs as concomitant medication may need to take tiagabine three times a day from the
beginning of treatment.

Side effects of tiagabine are primarily CNS-related and are more common during drug
titration; the main side effects are sedation, headache, tiredness and dizziness. Tremor,
diarrhoea, irritability, confusion, and depression are seen occasionally. Exacerbations of
seizures and cases of non-convulsive status epilepticus have also been reported.

Topiramate

Topiramate is licensed as a first-line drug for people with focal seizures with or without
secondary generalisation and for generalised seizure disorders.

Recommended doses are between 75 and 300 mg, although some people may derive benefit
from a dose that is outside this range. The recommended starting dose for most people is 25 mg
once daily, titrating upwards every two weeks in 25 mg/day increments up to 200 mg/day in
two divided doses. After that, the dose can be increased by 50 mg each week until seizure
control is achieved or side effects develop.

Topiramate exhibits linear pharmacokinetics with low levels of protein binding. It has minimal
interaction with other AEDs, although hepatic enzyme inducers accelerate its metabolism.
Because of this, topiramate doses may need to be adjusted downwards if people are coming off
carbamazepine or phenytoin.

Most of the acute and dose-related side effects of topiramate are CNS-related including
dizziness, drowsiness, headaches, irritability, cognitive slowing and speech impairment. These
are usually transient and in some people seem to be related to the dose and rate of titration.
Paraesthesia and nephrolithiasis have also been reported and are likely to be due to topiramate’s
carbonic anhydrase inhibitory action. People starting topiramate should increase their fluid
intake to reduce the risk of kidney stones. Initial weight loss is seen in up to 40% of people and
is usually not problematic. No idiosyncratic side effects have yet been described. Topiramate
is teratogenic in some animal models and it is not recommended as a first-line option in women
of childbearing potential.

Vigabatrin

Vigabatrin is now a last resort treatment for people with focal seizures. It is, however, still a
first-line treatment for infantile spasms, particularly those associated with tuberous sclerosis. It
has no use in primary generalised epilepsy and may worsen myoclonic seizures. Tolerance may
develop in up to one-third of initial responders.

The recommended dose is 10002000 mg/day, although doses of up to 4000 mg/day in two
divided doses can be used if necessary. Treatment should be started with a low dose (250500
mg/day), and titrated slowly upwards over a period of several weeks until therapeutic response
is achieved. Too rapid titration may be associated with an increased incidence of adverse events.

The addition of vigabatrin reduces plasma concentrations of phenytoin. The mechanism is
unknown but may be due to decreased phenytoin absorption. Usually this has no clinical
significance, but occasionally an increase in phenytoin dose is necessary if seizures increase a
few weeks after the introduction of vigabatrin. The corollary of this effect is that plasma
phenytoin concentrations rise after the withdrawal of concomitant vigabatrin therapy.
Vigabatrin has no other known pharmacokinetic interactions. There is no need to measure the
plasma concentration to guide dosing.