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.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |