Advances and limitations in pharmacotherapy of epilepsy

Abstract

Epilepsy is a chronic neurologic disorder that affects about 0.7% of the population. Patients with epilepsy suffer from recurrent seizures, which can be focal or generalized in nature. The third-generation of anticonvulsant drugs includes lacosamide, rufinamide, vigabatrin, retigabine, perampanel, eslicarbazepine acetate, brivaracetam, and stiripentol. Other compounds, such as ganaxolone, cannabidiol, selurampanel, and everolimus among others, with different mechanisms of action are currently in clinical development. Furthermore, numerous compounds or classes of compounds are investigated in preclinical studies. Nevertheless, about 30% of epilepsy patients suffer from uncontrolled seizures despite pharmacotherapy, including the third-generation of anticonvulsant drugs. Additionally, the occurrence of adverse drug effects is responsible for poor compliance as well as discontinuation of the therapy, in up to 25% of patients before having reached the effective dose amount. Neuropsychiatric undesirable effects include depression, aggression, irritable mood, anxiety, mood instability, paranoid ideation, delusions, hallucinations. Moreover, suicidal ideation and behavior have been reported in patients treated with anticonvulsant drugs.