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Sopuluchukwu Udodi P, Izuchukwu Abugu J, Ebube Udodi R, Chikere Ofoego U, Christian Okafor E, Emmanuel Orji C, et al . The Neurotoxic Mechanisms of Valproic Acid and Their Association With Neurodevelopmental Disorders: A Narrative Review. BCN 2026; 17 (1) :25-38
URL: http://bcn.iums.ac.ir/article-1-3120-fa.html

Valproic acid (VPA), which is an anticonvulsant and mood stabilizer, has been applied in treating several neurological and psychiatric conditions. However, severe neurotoxic side effects may result from its use, especially when taken at certain developmental stages of a child’s brain. Consequently, the present narrative review aimed not only to summarize what is presently known about the neurotoxicity of VPA and the related neuropsychiatric disorders, but also to focus on potential interventions. Most of VPA’s neurotoxic effects are due to its ability to increase reactive oxygen species (ROS) production, cause mitochondrial dysfunction, and alter epigenetics. It also facilitates neuronal damage by distorting the excitatory and inhibitory neurotransmission, increasing the excitotoxicity, oxidative stress, and mitochondrial dysfunction. These neurotoxic mechanisms are strongly associated with multiple neurodevelopmental disorders (NDDs). For example, prenatal VPA use is one of the common risk factors in autism spectrum disorder (ASD) that is correlated with complex social and communication deficits. VPA, which is used to treat epilepsy, may paradoxically increase seizure propensity by affecting neuronal excitability and synaptic input. Understanding these pathways can help reduce VPA’s neurotoxicity without diminishing its efficacy in sensitized children.