Two clinical cases reveal concerning interactions between GLP-1 receptor agonists and psychiatric medications. A woman with bipolar disorder developed lithium toxicity after starting tirzepatide, requiring discontinuation of both drugs for levels to normalize. A man with major depression experienced mood lability, irritability, and aggression on tirzepatide that resolved when stopped. These represent the first documented cases of GLP-1 drugs potentially altering psychiatric medication metabolism through gastrointestinal effects. The implications extend far beyond these isolated reports. With over 15 million Americans now using GLP-1 drugs like Ozempic and tirzepatide, and psychiatric medication use affecting roughly 20% of adults, the overlap is substantial. The lithium case is particularly alarming since toxicity can be life-threatening, causing kidney damage and neurological complications. The mechanism likely involves GLP-1's slowing of gastric emptying, altering drug absorption rates. For clinicians, this demands heightened vigilance when prescribing these popular weight-loss drugs to patients on mood stabilizers, antidepressants, or antipsychotics. While preliminary, these findings suggest GLP-1 drugs may not be the universally safe interventions they're often portrayed as, especially in psychiatrically complex patients requiring careful medication balance.