Serotonin and sudden unexpected death in epilepsy
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Updated: Jan 1, 2026

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Published on: February 28, 2025
Alexandra N Petrucci1, Katelyn G Joyal1, Benton S Purnell1
1Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52242, United States of America; Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States of America.
Abstract:
Epilepsy is a highly prevalent disease characterized by recurrent, spontaneous seizures. Approximately one-third of epilepsy patients will not achieve seizure freedom with medical management and become refractory to conventional treatments. These patients are at greatest risk for sudden unexpected death in epilepsy (SUDEP). The exact etiology of SUDEP is unknown, but a combination of respiratory, cardiac, neuronal electrographic dysfunction, and arousal impairment is thought to underlie SUDEP. Serotonin (5-HT) is involved in regulation of breathing, sleep/wake states, arousal, and seizure modulation and has been implicated in the pathophysiology of SUDEP. This review explores the current state of understanding of the relationship between 5-HT, epilepsy, and respiratory and autonomic control processes relevant to SUDEP in epilepsy patients and in animal models.
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