Anhedonia nonresponse to short-term ketamine administration for treatment-resistant bipolar depression.
Therapeutic advances in psychopharmacology – January 01, 2026
Source: PubMed
Summary
Nearly half of patients (45.2%) with treatment-resistant bipolar depression (TRBD) did not experience relief from anhedonia following short-term ketamine psychopharmacology. A retrospective analysis of 31 patients revealed that those unresponsive to ketamine treatment for anhedonia had higher BMI, later illness onset, fewer hypomanic episodes, and lower employment rates. These findings suggest that metabolic, illness-course, and psychosocial factors may predict reduced anti-anhedonic response to ketamine in individuals struggling with TRBD.
Abstract
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. This study aimed to identify clinical and sociodemographic characteristics that are associated with nonresponse of anhedonia following short-term ketamine treatment in TRBD. 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. 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. Fourteen patients (45.2%) did not respond. Nonresponders had higher BMI, later illness onset, fewer hypomanic episodes, and lower employment rates. Metabolic, illness-course, and psychosocial factors may predict reduced anti-anhedonic response to ketamine in TRBD.