Lithium Toxicity Following Initiation of Semaglutide in a Patient With Bipolar Disorder: A Case Report.

Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for type 2 diabetes mellitus and obesity, including among patients with severe mental illness. Their effects on gastrointestinal motility, oral intake, and volume status raise concern for interactions with drugs with narrow therapeutic indices that are cleared almost entirely by the kidney, such as lithium. We describe a 69-year-old woman with bipolar disorder, stable for several years on lithium, who presented with acute confusion, dysarthria, and expressive aphasia. A stroke protocol was activated, and noncontrast head CT, CT angiography of the head and neck, and MRI of the brain showed no acute infarct or hemorrhage. Semaglutide had been initiated approximately one month earlier for weight management, and she had experienced substantial weight loss with persistent nausea, intermittent vomiting, and reduced oral intake. Serum lithium was elevated above the reference range, accompanied by a reduced estimated glomerular filtration rate and biochemical findings suggestive of volume depletion. Lithium was held, and intravenous fluids were administered; renal function improved and the neurologic deficits resolved. Lithium was subsequently resumed at a reduced dose without recurrence. In this patient, initiation of semaglutide was temporally associated with lithium toxicity in the setting of gastrointestinal intolerance, reduced oral intake, and suspected volume depletion. Although a single case cannot establish causality, this observation supports closer lithium monitoring when initiating GLP-1 receptor agonists and during dose escalation.