Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients, occurring even more frequently in cases with anti-epileptic drug resistance. Despite some advancements in characterizing SUDEP, the underlying mechanism remains incompletely understood. This review summarizes the latest advances in our understanding of the pathogenic mechanisms of SUDEP, in order to identify possible targets for the development of new strategies to prevent SUDEP. Based on our previous research along with the current literature, we focus on the role of sleep-disordered breathing (SDB) and its related neural mechanisms to consider the possible roles of monoaminergic neurons in the modulation of respiration during sleep and the occurrence of SUDEP. Overall, this review suggests that targeting the monoaminergic neurons is a promising approach to preventing SUDEP. The proposed roles of SDB and related monoaminergic neural mechanisms in SUDEP provide new insights for explaining the pathogenesis of SUDEP.

AAS, ascending arousal system; VTA, ventral tegmental area; DRN, dorsal raphe nucleus; LC, locus coeruleus; PBC, pre-Bötzinger complex; DA, dopamine; D2R, D2 receptor; NE, norepinephrine; α1R, α1 receptor; βR, βreceptor; 5-HT, serotonin; 5-HTR, serotonin receptor; GABA, GABAergic interneurons; SDB, sleep-disordered breathing; OSA, obstructive sleep apnea; CSA, central sleep apnea; (+), Activation; (-), Inhibition.