Neuropsychiatric, Neurocognitive And Quality Of Life Outcomes In Patients With Epilepsy Treated With Levetiracetam (Keppra) Verses Older AEDs As First Substitution Monotherapy.

Epilepsy is a chronic condition with complex effects on a person’s social, vocational, and psychological function. Physicians are increasingly recognizing that there is more to managing epilepsy than seizure control alone. Side effects of Anti epileptic drugs (drugs used to treat epilepsy), psychiatric and cognitive problems associated with epilepsy are increasingly recognised. Cognition can be loosely explained as an individual’s mental ability to process information and accounts for virtues such as memory, worldly knowledge and problem solving to name a few. It is becoming increasingly recognized that these problems could adversely influence the quality of life of patients, even in those whose seizures are well controlled. The psychiatric and cognitive problems could be due to illness itself or could be due to the side effects of antiepileptic medications. By effectively managing these problems we could maximise the quality of life (QOL) and over all well-being of patients suffering with epilepsy. Only six antiepileptic drugs were available prior to 1990. In the last decade several new anti epileptic drugs have become available increasing our therapeutic options. There has been great deal of research into formulating better anti epileptic drugs, primarily spurred by the fact that the available anti epileptic drugs did not provide adequate control or patients’ were experiencing side effects from drugs. Older Anti epileptic drugs have many undesired side effects. As a group, they have been shown to adversely influence body’s ability to process bodily hormones and drugs. This leads to unwanted side effects such as sexual dysfunction, bone thinning (Osteoporosis), and failure of oral contraceptives to name a few. Side effects such as drowsiness, lethargy and psychiatric and cognitive problems are also more common with older anti epileptic drugs. The newer drugs as a group overall have been shown to have less side effects and are better tolerated. The efficacy of newer drugs is comparable if not superior to older drugs but with less side effects. It is a well-known fact that approximately two thirds of patients would become seizure free with the first or second drug given to them. In recent studies, these treatment responsive patients responded to low doses of essentially all the anti epileptic drugs studied, both old and new. Because these patients will remain on the initial or second therapy for several years, and because they will respond to most drugs, the burden is on the treating physician to select the anti epileptic drug that is most tolerable, has the lowest potential for harm, and has the least likelihood of negatively impacting quality of life.Despite their potential benefits, use of newer anti epileptic drugs thus far is largely limited to refractory cases and to tertiary centres. The newer drugs such as Levetiracetam (Keppra), have the potential to improve quality of life in subjects with epilepsy. The rationale of this project is to compare the tolerability, side effect profile and quality of life outcomes in treatment with levetiracetam versus the “older AEDs” - carbamazepine and valproate; the two drugs most commonly used as first line treatment. We hypothesize that levetiracetam’s efficacy and favourable side effect profile will enhance QOL and will improve health outcomes. We intend to test our hypothesis by prospective assessments of seizure control, cognitive and psychiatric effects and QOL. Cognitive assessments are done through a computerized battery of tests called IntegNeuro. We will also, as part of this study, perform a pilot study of to assess the utility of ocular motility (eye movement) testing as a practical method of assessing anti epileptic drug effects on cognitive performance. It is being increasingly recognized that subtle abnormalities of eye movements are seen in cognitive dysfunction. We intend to perform computerized eye movement testing in a subgroup of 20 patients randomized to each drug, and assess its use as an index of cognitive dysfunction that could be associated with anti epileptic drug use. Psychiatric and QOL assessments are done through well-validated questionnaires. The study population will be patients with epilepsy who have failed treatment with first anti epileptic drug. Failure is defined as lack of efficacy in controlling seizures or need to stop the drug because of side effects. Previous studies of Levetiracetam have been performed in either medically refractory patients who have taken multiple anti epileptic drugs or newly treated patients, whose clinical course is not yet clear. If positive the results of this study will provide evidence for the earlier use of newer anti epileptic drugs, in particular levetiracetam, especially in early stages of epilepsy and help improve the health outcomes of patients with epilepsy.