Real world effectiveness of maintenance ketamine infusions for treatment-resistant depression in major depressive disorder and bipolar disorder.
Sipan Haikazian, Roger S McIntyre, Shakila Meshkat, Kevin Kratiuk, Cristian-Daniel Llach, Diana Orsini, Sara Di Luch, Joshua D. Rosenblat
Psychiatry Research August 15, 2025 DOI: 10.1016/j.psychres.2025.116691 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective chart review Peer reviewed |
|---|---|
| Sample size | 135 |
| Population | Patients with treatment-resistant major depressive disorder (110) and treatment-resistant bipolar depression (25) who responded to acute ketamine infusions and received maintenance infusions |
| Duration | Several weeks and months (maintenance period) |
| Topics | Depression Esketamine Ketamine |
| Citations | 7 |
| Key findings | Depression and suicidality scores decreased after acute ketamine infusions and improvements persisted during maintenance treatment, with no suicidal behavior or addiction observed. |
Abstract
Antidepressant effects with sub-anesthetic doses of intravenous ketamine have been previously demonstrated. However, previous studies have primarily evaluated the efficacy of acute treatment protocols, with limited research on maintenance treatment. Moreover, controlled maintenance studies have only included patients with treatment-resistant Major Depressive Disorder (TRD), with no maintenance studies evaluating effects in bipolar disorder. Herein, we report the first study to evaluate maintenance ketamine infusions in patients with treatment-resistant bipolar depression (TRBD), in addition to a sample of patients with TRD. A retrospective chart review of patients receiving ketamine infusions from a community treatment centre was conducted. 110 TRD and 25 TRBD patients were included, all of whom responded to an acute course of ketamine infusions and later received maintenance infusions. Linear mixed models found that depression and suicidality scores, as measured by the Quick Inventory of Depressive Symptomatology (QIDS-SR16) assessment, were significantly decreased after an acute course of ketamine infusions, with improvements persisting while patients continued to receive maintenance infusions over several weeks and months. Similar observations were seen after analyzing weekly patient-reported clinical global impression scores. Ketamine was determined to be relatively safe, with zero cases of suicidal behaviour and addiction behaviour throughout treatment. One patient (4 %) diagnosed with TRBD underwent affective switching, with no further tolerability concerns following stabilization. These results provide preliminary support for the long-term clinical utility of maintenance ketamine infusions.
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 6
- Inflammation and treatment strategies for suicidal behavior. The World Journal of Biological Psychiatry June 1, 2026
- Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study. Psychiatry Research August 1, 2026
- Evaluating the abuse liability of ketamine in the treatment of mood disorders: A systematic review. Journal of Psychopharmacology June 24, 2026
- Progress, potential and pitfalls of ketamine as a treatment for depression Expert Opinion on Pharmacotherapy January 22, 2026
- Patient-centred education for ketamine and esketamine therapies in mood disorders. Therapeutic Advances in Psychopharmacology 2026
and 1 more in the library
Cites 28
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
and 23 more in the library