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remission with active management including alternative monotherapy or polytherapy, while
the remainder have refractory epilepsy and continue to have seizures. It is helpful to talk to
patients about these figures in general terms at the outset, particularly if they have factors that
suggest poor prognosis. Over-optimism can lead to disillusionment and poor adherence.

Choice of AED

Industry-sponsored phase 3 clinical trials of AEDs are designed to satisfy regulatory
requirements for drug licensing. For ethical reasons (one cannot randomise a patient to no
treatment) new AEDs can only be initially tested as add-on therapy, however this does not
mean they are necessarily unsuitable for monotherapy, just untested and unlicensed for such.
As experience is gained as add-on therapy and in further open studies, applications for the
monotherapy licence are made. Research participants in phase 3 trials are generally
individuals with highly refractory epilepsy (usually focal) and frequent seizures. New
medications are added into existing therapy and the randomised phase of the trial usually
lasts 3–4 months, with relatively rapid dose escalations. This is far removed from the typical
clinical scenario of an individual with newly diagnosed epilepsy starting their first AED in
monotherapy. The SANAD (Standard and New Antiepileptic Drug) study coordinated from
Liverpool aimed to address this8,9.

This large pragmatic study comprised two arms: arm A compared carbamazepine with
lamotrigine, topiramate, gabapentin and latterly oxcarbazepine8; arm B compared valproate
with lamotrigine and topiramate9. Arm A contained individuals with predominantly focal
epilepsy and arm B mostly generalised epilepsy (though unclassified epilepsies were also
entered into arm B). The study was randomised but not blinded, which gives a lower evidence
grade; however SANAD is by far the largest and best-conducted study of treatment in newly
diagnosed epilepsy available. And it confirmed what clinical experience suspected, i.e. no
new AED in the study was more effective than carbamazepine for focal epilepsy but
lamotrigine and oxcarbazepine were better tolerated. In arm B valproate was the most
effective drug. The SANAD study did not include the newest AEDs because they were not
widely available at the time. Another study (SANAD II) is now under way to establish the
place of levetiracetam and zonisamide compared to the established lamotrigine and sodium
valproate in the treatment new onset focal and generalised epilepsy.

AED therapy should be chosen according to the type of seizure and tailored to the individual.
It is important to characterise the seizure type and epilepsy syndrome and to avoid AEDs that
might exacerbate seizures, e.g. carbamazepine in absence or myoclonic seizures in the
idiopathic generalised epilepsies.

Cost is a factor that cannot be ignored and if standard cheaper medication is acceptable it
should be prescribed. Generic prescribing can be problematic, more so for those already
established on an AED, because minor changes in AED levels can result in breakthrough
seizures, and changes in brand should be avoided if at all possible.

Carbamazepine should be prescribed in the modified-release preparation as this reduces side
effects10. Individuals who cannot tolerate carbamazepine in whom it is effective may tolerate
oxcarbazepine, or possibly eslicarbazepine (this is not currently licensed for monotherapy in
the UK) though the long-term side effect of hyponatraemia and the risk of rash are seen with
both. Lamotrigine was originally promoted as ‘the AED for women’ and was said to have no
interactions with hormonal contraceptives. This has been shown not to be the case; it is now
known that lamotrigine levels can fall unpredictably when oestrogen-containing
contraceptives are used concomitantly11. Similarly lamotrigine levels can fall unpredictably
in pregnancy12.