Nonresponse to Ketamine in Treatment‐Resistant Bipolar Depression
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek, Michał Pastuszak, Krzysztof Pastuszak, Aleksander Kwaśny
Neuropsychopharmacology Reports July 20, 2025 DOI: 10.1002/npr2.70038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of a naturalistic study Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Patients with treatment-resistant bipolar depression |
| Intervention | Ketamine |
| Dose | intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg |
| Duration | Four-week ketamine regimen |
| Topics | Depression Ketamine Esketamine |
| Keywords | Depression economics Bipolar disorder Clinical psychology Keynesian economics Cognition |
| Citations | 3 |
| Registration | NCT04226963 NCT05565352 |
| Key points | Nonresponse to ketamine in treatment-resistant bipolar depression was associated with a higher number of psychiatric comorbidities and greater prior benzodiazepine use. |
Abstract
Objectives: Ketamine is a prototypical rapid-acting antidepressant for treatment-resistant bipolar depression (TRBD), yet many patients do not achieve a meaningful response. This study explored features of ketamine nonresponse in TRBD.
Methods: In a post hoc analysis of a naturalistic study, 35 TRBD patients received a four-week ketamine regimen (intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg). Response was measured using the Montgomery-Åsberg Depression Rating Scale, and baseline sociodemographic and clinical features were compared between responders and nonresponders.
Results: Fourteen patients (40%) were nonresponders. They had a higher median number of psychiatric comorbidities (2 vs. 1; p = 0.0366), were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%; p = 0.0153), and had greater prior benzodiazepine use (64.3% vs. 23.8%; p = 0.0332). No significant links emerged between individual comorbidities or baseline suicidality and response.
Conclusion: Ketamine demonstrates a favorable safety and tolerability profile for short time use in TRBD regardless of isolated baseline characteristics, although a more severe comorbidity burden and benzodiazepine use appear to be associated with nonresponse.
Trial Registration: NCT04226963 and NCT05565352.
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 |