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Chapter 29
New antiepileptic drugs
J.W. SANDER
UCL Institute of Neurology, University College London, National Hospital for Neurology
and Neurosurgery, Queen Square, London, and Epilepsy Society, Chalfont St Peter,
Buckinghamshire
New antiepileptic drugs (AEDs) are necessary for people with chronic epilepsy and for
improving upon established AEDs as first-line therapy. Since 2000, ten new AEDs have been
released in the UK. In chronological order these are: oxcarbazepine, levetiracetam,
pregabalin, zonisamide, stiripentol, rufinamide, lacosamide, eslicarbazepine acetate,
retigabine and perampanel. Two of these drugs, stiripentol and rufinamide, are licensed as
orphan drugs for specific epileptic syndromes. Another drug, felbamate, is available in some
EU countries. Their pharmacokinetic properties are listed in Table 1 and indications and a
guide to dosing in adults and adolescents are given in Table 2. Known side effects are given
in Table 3.
Complete freedom from seizures with the absence of side effects should be the ultimate aim
of AED treatment and the new AEDs have not entirely lived up to expectations. Only a small
number of people with chronic epilepsy have been rendered seizure free by the addition of
new AEDs. Despite claims to the contrary, the safety profile of the new drugs is only slightly
more favourable than that of the established drugs. The chronic side effect profile for the new
drugs has also not yet been fully established.
New AEDs marketed in the UK
Eslicarbazepine acetate
Eslicarbazepine acetate is licensed as an add-on for focal epilepsy. It has similarities to
carbamazepine and oxcarbazepine. As such it interacts with voltage-gated sodium channels
and this is likely to be its main mode of action. There are no head-to-head comparisions
between this drug and oxcarbazepine or carbamazepine but in the radomised clinical trial
response was seen in some people that had not responded to carbamazepine or oxcarbazepine.
Its tolerability and pharmacokinetic profile are similar to that of oxcarbazepine.
Lacosamide
Lacosamide is licenced as an add-on for focal epilepsy in people over the age of 16 years. Its
putative mode of action is not shared with any other currently available AEDs as it enhances
the slow inactivation of sodium channels.
The recommended doses are between 200 and 400 mg/day divided in two doses. It should be
started at 50–100 mg/day and increased by 50 mg per day every one or two weeks.
