Balancing efficacy and safety: The dual impact of antiseizure medications on the developing brain

The number of neurons in the developing brain is greater than typically found in adulthood, and the brain possesses delicate mechanisms to induce the death of excess cells and refine neural circuitry. The correct tuning between the processes of neuronal death and survival generates a mature and functional brain in its complexity and plastic capacity. Epilepsy is a highly prevalent neurological condition worldwide, including among young individuals. However, exposure to the main treatment approaches, the long-term use of Antiseizure Medication (ASM), during the critical period of development can induce a series of changes in this delicate balance. Acting by various mechanisms of action, ASMs may induce an increase in neuronal death, something that translates into deleterious neuropsychiatric effects in adulthood. Several investigations conducted in recent years have brought to light new aspects related to this dynamic, yet many questions, such as the cellular mechanisms of death and the pathophysiology of late effects, still have unresolved elements. In this review, we aimed to explore the mechanisms of action of the most widely used ASMs in the treatment of neonatal epilepsy, the broad aspects of neuronal death in the developing brain and the repercussions of this death and other effects in adulthood. We review the evidence indicating a relationship between exposure to ASMs and the manifestation of associated psychiatric comorbidities in adulthood and discuss some possible mechanisms underlying the induction of this process by morphological and physiological changes in the related behaviors.