Anhedonia nonresponse to short-term ketamine administration for treatment-resistant bipolar depression

Background: Anhedonia is a key symptom of bipolar depression and a target of ketamine's rapid antidepressant effects. However, many patients with treatment-resistant bipolar depression (TRBD) do not respond. Objectives: This study aimed to identify clinical and sociodemographic characteristics that are associated with nonresponse of anhedonia following short-term ketamine treatment in TRBD. Design: A retrospective analysis using data from two naturalistic, observational registries of 31 patients with TRBD and baseline anhedonia (Snaith-Hamilton Pleasure Scale (SHAPS) > 2). Patients received eight doses of ketamine (IV: 0.5 mg/kg; oral: 2.0-2.5 mg/kg) over a short-term treatment course. Methods: Patients were classified as responders or nonresponders based on a ⩾50% reduction in SHAPS score by the seventh ketamine dose. Groups were compared on baseline sociodemographic and clinical features. Results: Fourteen patients (45.2%) did not respond. Nonresponders had higher BMI, later illness onset, fewer hypomanic episodes, and lower employment rates. Conclusion: Metabolic, illness-course, and psychosocial factors may predict reduced anti-anhedonic response to ketamine in TRBD.