Background: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely used for the treatment of type 2 diabetes and obesity and has demonstrated benefits in metabolic and emerging psychiatric indications. However, concerns have arisen regarding potential neuropsychiatric side effects, including mood disturbances and suicidality. To date, no known cases have linked semaglutide to psychogenic non-epileptic attacks (PNEA), a subtype of functional neurological disorder.

Case Presentation: We present the case of a 58-year-old African American woman with a history of PNEA, post-traumatic stress disorder, traumatic brain injury, and type 2 diabetes who developed a marked exacerbation of her seizure-like episodes approximately 13 weeks after initiating semaglutide therapy. Prior to treatment, her PNEA episodes were infrequent and brief. Following semaglutide initiation, she experienced daily episodes lasting up to 35 minutes, accompanied by depressive symptoms. Neurological workup was negative, and EEG showed no epileptiform activity. Upon discontinuation of semaglutide and titration of antidepressant therapy, the patient experienced complete resolution of her functional seizures and significant improvement in mood.

Discussion: Although semaglutide is not known to cause PNEA, its ability to modulate central neurotransmission, particularly dopamine signaling and stress response pathways, raises the possibility of adverse neuropsychiatric effects in vulnerable individuals. This case parallels other reports of mood disturbances associated with GLP-1 RAs and expands the scope of potential neurologic effects. Additionally, it highlights the contrast between semaglutide's emerging psychiatric applications and its rare but serious adverse events.

Conclusion: This case may represent the first reported association between semaglutide and PNEA exacerbation. Clinicians should be aware of potential neurologic and psychiatric side effects in patients with a history of functional neurological disorders or mood instability. Close monitoring and individualized risk assessment are warranted, particularly in those with complex neuropsychiatric histories.

DOI: doi.org/10.63721/26JPIR0132

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