Central nervous system-related safety and tolerability of add-on ketamine to standard of care treatment in treatment-resistant psychotic depression in patients with major depressive disorder and bipolar disorder
Maria Gałuszko‐węgielnik, Katarzyna Jakuszkowiak‐wojten, Mariusz S. Wiglusz, Wiesław Jerzy Cubała, Michał Pastuszak
Frontiers in Neuroscience July 11, 2023 DOI: 10.3389/fnins.2023.1214972 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Inpatients with treatment-resistant unipolar or bipolar depression with psychotic features |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | 4-week intervention, twice-weekly infusions |
| Topics | Depression Ketamine Esketamine |
| Keywords | Tolerability Bipolar disorder Depression economics Clinical psychology Mania Adverse effect Mood |
| Citations | 8 |
| Key findings | Ketamine infusions did not exacerbate psychotic or dissociative symptoms in treatment-resistant psychotic depression. |
Abstract
Background: Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is frequently underdiagnosed and inadequately treated. Ketamine has demonstrated rapid and potent antidepressant effects in clinical studies, while exhibiting a favorable safety and tolerability profile. Although there is limited literature available on the use of ketamine in psychotic TRD, reports on its efficacy, safety, and tolerability profile are of great interest to clinicians. The aim of this study is to investigate the relationship between dissociative symptomatology and psychomimetic effects in inpatients with treatment-resistant major psychotic depression and treatment-resistant bipolar psychotic depression, who receive intravenous ketamine treatment alongside psychotropic medication, both during and after treatment.
Materials and Methods: A total of 36 patients diagnosed with treatment-resistant unipolar (17 patients) or bipolar (18 patients) depression with psychotic features were treated with eight intravenous infusions of 0.5 mg/kg ketamine twice a week over 4 weeks. Ketamine was given in addition to their standard of care treatment. The severity of depressive symptoms was evaluated using the MADRS, while dissociative and psychomimetic symptoms were assessed using the CADSS and BPRS, respectively.
Results: There were no statistically significant changes observed in MADRS, CADSS, and BPRS scores within the study group during ketamine infusions. However, significant improvements in MADRS, CADSS, and BPRS scores were observed during ketamine infusions in both the unipolar and bipolar depression groups.
Conclusion: This study provides support for the lack of exacerbation of psychotic symptoms in both unipolar and bipolar depression.
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 |
Citations in the library
Cited by 5
- Comparing the adverse effects of ketamine and esketamine between genders using FAERS data. Frontiers in Pharmacology 2024
- Polish standard of treatment with racemic ketamine for patients with depressive disorders developed by a Working Group appointed by the National Consultant in the field of psychiatry. Psychiatria Polska June 30, 2024
- Psychotic-Like Experiences in Young Recreational Users of Ketamine: A Case Study. Journal of Psychoactive Drugs January 8, 2025
- [Intravenous Subnarcotic Ketamine Infusions for Treatment-Resistant Depression: Historical Development, Comparison with Esketamine Nasalspray, and Prospects]. Fortschritte der Neurologie · Psychiatrie June 8, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
Cites 20
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 15 more in the library