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monotherapy in both focal and primary generalised tonic-clonic seizures34 and also in treating
Dravet syndrome. The drug does appear to be associated with a number of acute and
predominantly dose-related side effects, particularly on the central nervous system. These
include dizziness, drowsiness, irritability, ‘fatigue’, word-finding difficulties/mild cognitive
impairment and, rarely, acute depressive and psychotic illness. These can be minimised by
slow introduction. Paraesthesiae, renal calculi and glaucoma have also been reported but
predominantly in adults; theoretically there is an increased incidence of renal calculi if children
are receiving a combination of either topiramate and zonisamide or topiramate with the
ketogenic diet over a long period (in excess of 12 or 18 months). Insomnia, anorexia and weight
loss are additional reported side effects with topiramate34.

There are few randomised clinical data on the use of tiagabine34 in children. As with all new
AEDs the drug has been shown to be more effective than placebo in suppressing focal onset
seizures in adults and some adolescents, without apparently causing any severe adverse
effects35,36. Like vigabatrin, tiagabine also has a direct effect on GABA-ergic
neurotransmission (and GABA levels) and although it is theoretically possible that tiagabine
might also affect visual field function, reports suggest that this drug does not produce the same
visual field defect that is seen with vigabatrin. A number of anecdotal reports have suggested
that the drug may precipitate non-convulsive status epilepticus37,38.

Oxcarbazepine, structurally similar to carbamazepine, was licensed for use in the UK in 2002.
Its spectrum of action is almost identical to carbamazepine, but by not being metabolised to
the 11-epoxide metabolite it is associated with fewer adverse side effects than carbamazepine
(i.e. less ataxia, diplopia and nausea). However, hyponatraemia is reported to occur more
frequently with oxcarbazepine – although rarely with any significant clinical effects. The drug
is available as a standard (not slow or sustained) release tablet and liquid suspension. Finally,
there is some evidence that oxcarbazepine will not be complicated by an idiosyncratic rash,
even if the child has previously developed a rash with carbamazepine. Like carbamazepine,
oxcarbazepine may exacerbate the absence and myoclonic seizures that occur in the generalised
epilepsies39.

There is a clear dose-response relationship with lamotrigine, gabapentin, topiramate,
levetiracetam and probably pregabalin, tiagabine and zonisamide but not with vigabatrin39, and
none appear to be associated with either significant tolerance or tachyphylaxis. Finally, there
is as yet no established plasma ‘therapeutic range’ for these new drugs; and as there is no
correlation between plasma levels of vigabatrin and its clinical efficacy (due to its
pharmacokinetic properties), such measurements are not helpful as a guide to dosage. Whether
a random level can be usefully used to ascertain compliance remains to be determined –
although this is probably useful where major non-compliance is possible.

Until 1994/5 felbamate was available in the UK on a compassionate, named-patient basis. Early
reports from the US had suggested that it was effective for focal seizures in adults40,41 and
generalised seizures associated with the Lennox-Gastaut syndrome in children43.
Unfortunately, a large number of patients developed aplastic anaemia, some with a fatal
outcome. A severe, presumed idiosyncratic, hepatitis has also been reported. As a result of
these serious adverse reactions, the drug is only available in the UK on a limited named-patient
basis. However, in the US, the prescribing of felbamate continues to increase (slowly), but
obviously with close monitoring of haematological and hepatic function. This re-emergence of
felbamate has not been reported to be accompanied by a corresponding increase in additional
cases of aplastic anaemia or hepatitis.

Zonisamide appears to have a broad spectrum of action, if data from Japan and the USA (where
the drug has been used for over a decade) are to be believed, with reported benefits in treating