Symptom modulation and tolerability of intravenous ketamine in treatment-resistant bipolar depression: A retrospective study.
Alessandro Cuomo, Simone Pardossi, Giovanni Barillà, Pietro Carmellini, Bernardo Firenzuoli, Francesca Tarantino, Rebecca Tinturini, Andrea Fagiolini
Journal of Affective Disorders May 1, 2025 DOI: 10.1016/j.jad.2025.01.059 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 59 |
| Population | Patients with treatment-resistant bipolar I or bipolar II disorder in a current depressive episode |
| Intervention | Intravenous ketamine |
| Dose | 0.8 mg/kg |
| Duration | Four weeks |
| Topics | Depression Ketamine Esketamine |
| Keywords | Bipolar disorder Mental health treatment Ketamine therapy Bipolar depression Suicide prevention Sleep disorders |
| Citations | 7 |
| Key findings | Intravenous ketamine significantly reduced depressive symptoms, inner tension, sleep disturbance, and suicidal ideation without causing manic switches in treatment-resistant bipolar disorder patients. |
Abstract
Ketamine's use in treating bipolar depression must account for risks, such as switching to manic episodes or worsening symptoms. This study examines ketamine's impact on depressive symptoms, focusing on 'inner tension,' 'sleep reduction,' and 'suicidal ideation' over four weeks in treatment-resistant bipolar disorder (TR-BD) patients. Fifty-nine patients with TR-BD were treated consecutively with ketamine (avg dose 0.8 mg/kg). Results showed significant reductions in MADRS scores without manic switches. Ketamine was well-tolerated despite polypharmacy. Antidepressant treatment of bipolar depression requires great caution because of the risk of switching to manic-mixed episodes and worsening of symptoms such as internal tension, psychomotor agitation, and suicide risk. The aim of this study was to evaluate the efficiency and tolerability of intravenous ketamine in patients with bipolar I or bipolar II disorder and a current treatment-resistant depressive episode (TR-BD), with the aim of examining: 1) the risk of manic switches; 2) the effect on global depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS); and 3) the specific effects on the MADRS items of internal tension, sleep disturbance, and suicidal ideation over a four-week period. Fiftynine patients with TR-BD (51.4 ± 12.3 years; 30 % female) treated consecutively with intravenous ketamine (mean dose 0.8 mg/kg) were included in this study. No ketamine-treated patient experienced a manic switch during the observation period. A statistically significant decrease (i.e., improvement) in MADRS global score and scores on the Internal Tension, Reduced Sleep, and Suicidal Ideation items was observed from the second week, with no evidence of worsening of the above symptoms. Patient-reported adverse events were generally mild to moderate.
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 |