Sigma-1 receptor antagonism as a potential mechanism of sertraline-associated Alice in Wonderland syndrome.

Recent pharmacovigilance data identified sertraline as the only SSRI associated with Alice in Wonderland syndrome (AIWS) in adults. This commentary proposes sigma-1 receptor antagonism, together with dopamine transporter inhibition, as plausible mechanisms linking sertraline to transient perceptual distortion and cortical network instability. Integrating molecular, neurophysiological, and neuroanatomical evidence, this perspective highlights the need for mechanistic and pharmacogenomic studies to clarify causality and improve the safety of serotonergic pharmacotherapy.