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After the introduction of valproate in 1973, excluding benzodiazepines, there was a 19 year gap before the introduction of vigabatrin, the first in a series of new antiepileptic drugs to be developed and licensed. At the time of writing gabapentin, lamotrigine, oxcarbazepine, tiagabine, and topiramate have a licence in the United Kingdom. Zonisamide and levetiracetam are licensed in some countries outside the United Kingdom. In this article, we review some of the evidence for the effectiveness and tolerability of these new drugs. We also attempt to draw attention to lessons learned and the conflict between the needs of the pharmaceutical industry, the clinician, and the patient.
New antiepileptic drugs as add-on treatments
DRUG REFRACTORY LOCALISATION RELATED EPILEPSY
New antiepileptic drugs are licensed as add-on treatments in the first instance, efficacy and safety having been demonstrated in randomised placebo controlled add-on trials, with additional safety data predominantly derived from follow on studies. Results from follow on studies are often difficult to interpret because comparisons are no longer randomised.
Trials usually recruit patients with drug refractory partial seizures. Patients are first of all observed during a prerandomisation baseline period of 8–12 weeks duration. Provided they have a sufficient a number of seizures (usually four a week), they are randomised to have either active drug or placebo added to their regime, and are followed up for 12–16 weeks. Efficacy is assessed by comparing individual patient's seizure frequency during the treatment period with the baseline period. Median reduction in seizure frequency and the number of patients with a 50% or greater reduction in seizure frequency (responders) are usually reported as efficacy outcomes.
The table summarises the results of intention to treat analyses from a systematic review of placebo controlled add on studies investigating gabapentin, lamotrigine, tiagabine, topiramate vigabatrin, and zonisamide in patients with drug refractory localisation related seizures,1 2 and in addition shows data …