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 via PubMed
Summary
AI-generated from the abstractIn patients with treatment-resistant bipolar disorder, intravenous ketamine (average dose 0.8 mg/kg) significantly reduced depressive symptoms, including inner tension, sleep reduction, and suicidal ideation, over four weeks without triggering manic switches. Fifty-nine patients were treated consecutively, and improvements in Montgomery-Åsberg Depression Rating Scale scores were observed from the second week onward. Adverse events were generally mild to moderate. The findings suggest ketamine can be a well-tolerated option for bipolar depression when carefully monitored, though caution is warranted due to the inherent risk of mood switching in bipolar disorder.
Study at a glance
| 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 |
| Keywords | Bipolar disorder Mental health treatment Ketamine therapy Bipolar depression Suicide prevention |
| Citations | 7 |
| Key finding | 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.