Drug treatment of epilepsy

British Medical Journal, Jan 9, 1999 by Morgan Feely

For optimal phenytoin treatment, the patient's blood phenytoin concentrations must be monitored at some point. Indeed, a standard starting dose (for example 300 mg/day in an adult) has the potential to produce a concentration that is either too high or too low in over half of the population. It is therefore advisable to check the blood phenytoin concentration about two weeks after starting treatment.

Although few British specialists recommend phenytoin nowadays, it is still widely used, and many doctors are likely to encounter patients taking it.[5] Doctors still need to know enough about phenytoin to be able to adjust the dose correctly. We should not abandon phenytoin. It may still have a place in severe epilepsy when other, "kinder," treatments have failed, and its effects on physical appearance are less evident in elderly people, among whom it seems to be as well tolerated as valproate.[4] Phenytoin too is teratogenic; its effects include cardiac defects and cleft lip or palate.

New drugs

Four new drugs for epilepsy (vigabatrin (Sabril),[6-8] lamotrigine (Lamictal),[6 7 9] gabapentin (Neurontin),[6 7 10 11] and topiramate (Topamax)[6 7 12]) have been licensed in the United Kingdom within the past 10 years. (Another new drug, tiagabine (Gabitril), has just come on the market.[6]) All four drugs were licensed as "add on" treatments and are still used as such, but lamotrigine is now licensed as a monotherapy too. Though there are some differences between these drugs with regard to less common types of epilepsy,[6 7] they are all competing for a market share in the treatment of patients with partial seizures, with or without secondarily generalised tonic-clonic seizures, who have not responded to drugs such as carbamazepine and valproate.

None of these newer drugs is best in all or most cases; any one of them may work in cases where others have not, and in many cases of severe epilepsy none will prove satisfactory. There have not been any head to head trials comparing these drugs, and there is no scientific basis for stating that one is more effective than another.[13] That is not to say that experienced epilepsy specialists regard them as pretty much the same. Brodie has produced a "star rating system" covering the new drugs and also the older treatments.[14] Additional information, including many practical points on using these new drugs, can be found in a recent article.[7]

Lamotrigine

Lamotrigine has been on the market for about seven years.[6 7 9] AS time has passed, specialists have been prescribing it more often and earlier, sometimes as the first treatment. One of the main advantages of lamotrigine is that it causes little cognitive impairment or overt sedation compared with other treatments.[6 9] It sometimes has an arousing or alerting effect. In some patients, mainly elderly people, this may manifest itself as unwanted agitation. Lamotrigine has a wide spectrum of activity. The chief drawback is the risk of allergic reactions. These occur less often than is the case with carbamazepine, but they are more often severe and can be life threatening, although this is rare.