Lithium toxicity following initiation of tirzepatide in a patient with bipolar I disorder

Abstract

Lithium has a narrow therapeutic window, with a therapeutic range for maintenance of 0.6 to 1.2 mmol/l, and toxicity usually occurs at concentrations of 1.3 mmol/l or greater. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have seen a marked rise in use for both diabetes and weight management, and an emerging body of case reports has described lithium toxicity associated with their use, predominantly with semaglutide. A 31-year-old man with a ten-year history of bipolar I disorder. His maintenance psychiatric medications included lithium carbonate ER 900 mg by mouth at bedtime daily. Approximately three months prior to presentation, tirzepatide 10 mg/0.5 ml was initiated subcutaneously once weekly for weight management. His lithium level at the time of initiation was 0.9 mmol/l. Three months after initiation, he began reporting a general sense of not feeling well, along with brain fog, dizziness, and gait disturbance, with good oral fluid and food intake throughout this period and no recent dietary or fluid intake pattern changes. A lithium level obtained at that time was found to be elevated at 1.7 mmol/l. Lithium was reduced to 300 mg daily for two weeks, and tirzepatide was held. A repeat lithium level two weeks later was 0.8 mmol/l. Lithium was then restarted at the original dose of 900 mg daily, and tirzepatide was subsequently discontinued. This case adds to a growing body of literature describing lithium toxicity with GLP-1 RA use, and for occurring in the absence of the gastrointestinal symptoms typically implicated in this interaction. Clinicians should maintain a high index of suspicion for increased lithium levels in patients with GLP-1 RA, with proactive rather than symptom-triggered lithium monitoring.