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 |