There is a growing literature on the concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with psychiatric disorders, and their safety and risks, in addition to potential therapeutic benefits in some disorders. The 2 cases presented in this issue report on potential adverse reactions from the combination of a GLP-1 RA and the patient's current psychiatric medication regimen. The first case involves a woman with bipolar disorder who developed lithium toxicity after being started on tirzepatide, which normalized after both medications were discontinued. The second case reports on a man with major depressive disorder who developed mood lability, irritability, and aggression after starting tirzepatide, which abated after the medication was stopped. These cases highlight the importance of monitoring all patients' medications to ensure that a GLP-1A RA does not affect the metabolism of medications through its potential gastrointestinal effects, while also evaluating any possible mood changes that may occur with this class of medications, despite growing evidence that they are not associated with worsening depression or suicidal thoughts. Further studies are needed to better understand the effects of GLP-1A RAs in patients with comorbid psychiatric disorders.
Amir Garakani (2026) studied this question.