Current Developments in Epilepsy Treatment
Current Developments in Epilepsy Treatment
Epilepsy includes a heterogeneous group of disorders, affecting approximately 0.8% of the population, and sharing in common the presence of recurrent seizures. Most patients with epilepsy can be controlled with anti-epileptic drugs (AEDs), and many of them can eventually discontinue their medication. However, seizures cannot be controlled in approximately 30% of patients. As multiple molecular mechanisms are involved in the generation of epileptic seizures there are no expectations that a single therapeutic approach will ever be effective in all types of epilepsy. In addition, personal susceptibility to different agents further supports the need for multiple therapies to treat people with epilepsy. Therefore, current development in epilepsy treatment follows different approaches and lines of research, and when available for clinical use, new therapeutic approaches provide benefit to a group of patients, sometimes in clinical situations that were not initially considered the therapeutic target. Application of available therapies is usually different in new onset epilepsy than in patients with difficult to treat epilepsy.
First Seizure and New Onset Epilepsy
When a patient has suffered the first epileptic seizure, a decision whether to treat or not is based on the risk of seizure recurrence and individual characteristics. A recent study demonstrates that initiating AEDs after a first seizure reduces the risk of seizure recurrence and generalised tonic-clonic seizures during the period of treatment, and concludes that treatment after a first seizure may be advised in patients with abnormal neurological examination, intellectual disability or an abnormal electroencephalogram (EEG). This approach to patients with a first seizure is further supported by a new definition of epilepsy from the International League Against Epilepsy. According to this definition, epilepsy is a disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition. This definition requires the occurrence of at least one epileptic seizure. Diagnosing the type of epilepsy after a first seizure is possible in 75% of patients, while in the remaining 25% it is not possible to determine whether it is a focal or generalised epilepsy. The distinction is clinically relevant since patients with idiopathic generalised epilepsy can suffer seizure worsening and even non-convulsive status epilepticus when treated with certain AEDs, mostly carbamazepine and phenytoin. Therefore, it is usually advised to initiate treatment with broadspectrum AEDs in patients in whom the diagnosis of the epilepsy type is in doubt. In addition to valproic acid, lamotrigine, levetiracetam and topiramate are broad spectrum AEDs licensed for initiation of treatment in new onset epilepsy. Other drug and patient characteristics should be considered at the time of selecting an AED; important factors are co-morbidity, drug interactions, age, sex and weight status. In fact, differences in efficacy among AEDs are small, while differences in side effect profile and potential interactions are more pronounced, representing a more important factor at the time of AED selection. Among these, cognitive side effects are especially important to consider; however, no adequate comparative studies are available to determine with the highest degree of clinical evidence which AEDs have less cognitive side effects. In this scenario a pragmatic approach is recommended; this includes monitoring cognitive function and side effects when initiating treatment and considering AED substitution when cognitive or other problems are identified. Based on clinical observation, gabapentine, lamotrigine, levetiracetam, oxcarbazepine and tiagabine are considered to have a lower risk of causing cognitive side effects compared with other AEDs.
