Resolution of anhedonia-like symptoms in patients treated for obesity with tirzepatide: A three-case series.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP1RAs) have demonstrated substantial efficacy for obesity and metabolic disease treatment, with emerging evidence suggesting effects on reward-processing pathways and motivated behaviors. Although reductions in food craving and addictive behaviors may be beneficial, some patients anecdotally report diminished motivation and anhedonia-like symptoms during high-dose therapy. This case series highlights a potentially underrecognized neurobehavioral effect associated with high-dose tirzepatide and explores clinical management strategies. Case presentation: Three female patients with obesity treated with high-dose tirzepatide (15 mg·week Interventions and outcomes: All patients underwent tirzepatide dose reduction to 10 mg·week Conclusion: This case series suggests that anhedonia-like symptoms may occur in a subset of patients receiving high-dose tirzepatide, potentially related to GLP1RA-mediated modulation of mesolimbic dopaminergic pathways. Clinicians should consider monitoring for changes in motivation and reward perception during treatment, particularly at higher doses. Dose reduction, with or without adjunctive dopaminergic therapy such as bupropion, may alleviate symptoms while preserving therapeutic benefits.