Anhedonia nonresponse to short-term ketamine administration for treatment-resistant bipolar depression.
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek, Michał Pastuszak, Krzysztof Pastuszak, Aleksander Kwaśny
Therapeutic Advances in Psychopharmacology 2026 DOI: 10.1177/20451253251412629 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective analysis of two naturalistic, observational registries Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Patients with treatment-resistant bipolar depression and baseline anhedonia |
| Intervention | Ketamine |
| Dose | IV: 0.5 mg/kg; oral: 2.0-2.5 mg/kg |
| Duration | Short-term treatment course (eight doses) |
| Topics | Ketamine Depression Esketamine |
| Keywords | Anhedonia Psychopharmacology Treatment-resistant bipolar depression |
| Key findings | Higher BMI, later illness onset, fewer hypomanic episodes, and lower employment rates were associated with nonresponse of anhedonia to short-term ketamine treatment. |
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.