Neurosteroid Regulation of Seizures: Role of GABAA Receptor Plasticity

Abstract

Adverse effects of antiepileptic drugs (AEDs) are common and result in treatment discontinuation in up to 25 % of patients. The profile of adverse effects varies greatly among AEDs and markedly affects drug selection for individual patients. The most common adverse effects like cognitive impairment, coordination difficulties, and other CNS-related adverse effects are predictable, dose dependent, and reversible. They are of particular concern in patients who work or study. Idiosyncratic adverse reactions are unexpected events that cannot be explained by known mechanisms of action. Typically, they are not related to dose and they are associated with high risk of morbidity or even mortality. Some of them, like weight gain, can negatively affect treatment adherence. Many of AEDs increase the risk of congenital malformations or reproductive problems. New AEDs are usually better tolerated and some of them have no effect on hepatic drug-metabolizing enzymes which results in lower potential for drug interactions. Comparative, well-designed, and long-term trials are however needed to confirm better tolerability of the new AEDs and to assess their effect on quality of life, tolerability, and teratogenic potential.