Do new anticonvulsants affect cognitive function? Dr. W. McIntyre Burnham, Bloorview Epilepsy Research Program, University of Toronto
A number of anticonvulsants have been introduced in Canada in the past decade. They include clobazam (Frisium), vigabatrin (sabril), gabapentin (Neurontin), lamotrigine (Lamictal), topiramate (Topamax), and oxcarbazepine (Trileptal).
Other anticonvulsants have been approved for sale in the United States; they may soon be available in Canada. They include zonisamide (Excegran) and levetiracetam (Keppra). Of them, levetiracetam looks the most interesting. Oxcarbazepine and zonisamide work by the same mechanism as older drugs, while levetiracetam seems to have a novel mechanism of action.
Are the newer drugs better than the older, "tried but true" anticonvulsants that we use now? When these drugs began to appear in Canada in the 1990s, we sincerely hoped that they would suppress seizures that are resistant to older drugs. We hoped that they would reduce the number of people whose seizures resist drug control from 20-40% to 0%. This hasn't happened. While wonderful successes have occurred in individual patients, the total number of people with drug-resistant seizures has not decreased very much. Seizures that resist the older drugs tend to resist the newer ones. The newer drugs are as effective – but not more effective – than the older drugs.
Although they may not be more effective, newer drugs have a reputation for causing fewer side effects – of being easier to tolerate than older drugs. In particular, they have a reputation for causing fewer cognitive ("sedative") side effects. Is this reputation justified? If so, it might justify their greater cost.
Lars Brunbeck and Anne Sabers of the Danish Epilepsy Hospital have just published a review of newer drugs, with particular reference to their cognitive side effects. They say that the newer drugs – except for topiramate – have not displayed major effects on cognition, as measured by neuropsychological tests. Topiramate may cause problems, at least at the start of therapy. It is not clear whether these problems continue during prolonged treatment.
But are the newer drugs better than the older ones? In studies that compared the new and old, they state, "There is a tendency in favour of the new anticonvulsants in some of the studies."
So it appears that the newer drugs may be somewhat better. However, the difference is not very dramatic and did not show up in every study. What advice can a pharmacologist offer to people taking anticonvulsant medications?
If an individual is well controlled on the older drugs (e.g., phenytoin, valproate, carbamazepine) – and isn't experiencing serious side effects – he or she should probably stick to them. They are cheaper, and we pretty well know their side effects. The side effects of newer drugs are still turning up. If an individual is having seizures with older drugs – or suffering serious side effects – then he or she should probably talk to a doctor about trying a newer drug.
Originally published in Epilepsy Canada Lumina, Autumn 2002.
Dr. Burnham is the president of Epilepsy Ontario.
