Therapy Analysis - Epilepsy
Today's treatments
Following on from the discovery of phenobarbital and phenytoin, the therapeutic options for epilepsy have broadened further in recent decades. As of June 2009, Pharmaprojects' data shows 17 new chemical entities (NCEs) were launched for epilepsy worldwide since 1980. The 1990s saw a flurry of approvals for antiepileptic drugs in the US, including felbamate and gabapentin in 1993, lamotrigine in 1994, topiramate in 1996, tiagabine in 1997 and levetiracetam in 1999. Total numbers of launched antiepileptics (both NCEs and formulations) remained pretty steady between 1998 and 2005, with another spurt of new launches between 2006 and 2009. The latest antiepileptic NCE drugs, approved in 2009, are lacosamide and rufinamide, providing further treatment options for patients whose epilepsy is not controlled by existing medications.
The overwhelming majority of these drugs were developed by screening a wide array of chemical compounds using epilepsy animal models. This meant little was understood about the molecular mechanism behind the drugs' efficacy, even as they entered the market. Since then our understanding of the mechanisms involved has improved and it is accepted that these drugs fall largely into three groups: sodium channel inhibitors, GABA system modulators and calcium channel inhibitors (Graph 1).
Alternatives to pharmacological intervention have also been developed. These include brain surgery (both invasive and non-invasive), vagus nerve stimulation and ketogenic diet. Brain surgery is an effective option for patients with treatment-refractory focal epilepsy. Prior evaluation is used to locate the epileptic focus, which is then excised. A high fat, low carbohydrate 'ketogenic' diet has seen a resurgence in recent times and is primarily used to treat drug-resistant epilepsy in children. Vagus nerve stimulation is also used as an adjunctive treatment in intractable epilepsy, although little is understood about why it is effective.
