Page 308 - ILAE_Lectures_2015

However, a child with normal intelligence who experiences frequent absence and generalised
tonic-clonic seizures on waking may require treatment. Once a drug is started the objective is
to achieve complete seizure control using a single drug, without causing side effects, and to
use the most appropriate formulation to ensure that the child can actually take and absorb the
medication.

The identification of the syndrome or seizure type provides information on the prognosis of
the epilepsy and choice of AED. However, when prescribing for infants and young children
the selection of the most appropriate AED must take into account the safety profile of that drug
(i.e. the risk of and type of side effects) and also the available formulation of the drug.

This is particularly relevant in paediatric epilepsy where there is still a relative lack of
knowledge and understanding about possible long-term effects of AEDs on growth and
development, as well as concern about the short-term effects on behaviour, intellectual function
and patterns of sleep. Although the newer AEDs appear to have a more acceptable safety
profile, this optimism should remain somewhat guarded in view of the lack of any long-term
data. Justification for this caution is derived from experience with felbamate where aplastic
anaemia and hepatitis became manifest only a few years after its introduction in the early
1990s, and also with vigabatrin, where a characteristic bilateral visual field constriction was
identified only ten years after introduction.

Once the most appropriate AED has been selected, this should be used alone (monotherapy)
and in the lowest dose that controls the seizures without producing unacceptable side effects.
This should be possible in approximately 70% of children. In children under the age of 12
years, dosages are usually based on bodyweight (mg/kg) rather than numbers of
tablets/capsules (Table 2); this is clearly important in view of the wide age range of children
treated and their different metabolic rates. For example, neonates, infants and children under
the age of two frequently require relatively higher doses than older children and adolescents
because of a higher rate of drug clearance.

When initial seizure control is suboptimal, or the AED has an obvious dose-response
relationship, the dosage should be increased gradually until either seizure control is achieved
or unacceptable side effects develop. If side effects occur before control is reached, the child
will require either a different AED (substitute drug) or an additional AED (polytherapy). The
choice of this second AED will depend upon the same criteria used to select the first but also
on the likelihood of any potential interaction between the two drugs. How the change in AED
therapy is effected depends on the child and the experience and beliefs of the clinician. If there
has been some initial seizure control with the first AED it would be reasonable to add the next
most appropriate AED, without withdrawing the first. If complete seizure control is then
achieved, attempts to withdraw the first drug could be undertaken after a seizure-free period of
between two and three months. If the initial AED has been wholly ineffective, it would seem
logical to simultaneously replace the first drug with the second, thus maintaining monotherapy.

Polytherapy (‘polypharmacy’)

In some children, polytherapy with two AEDs is justified as this may result in additional (even
complete) seizure control in another 10% of children. However, the problems of polytherapy
include: pharmacodynamic interactions potentially reducing the effectiveness of each drug,
difficulty in interpreting the effect of each drug, cumulative toxicity, and increased risk of