An Update on the Efficacy of Single and Serial Intravenous Ketamine Infusions and Esketamine for Bipolar Depression: A Systematic Review and Meta-Analysis

Ketamine can rapidly reduce depression and suicidal thoughts in treatment-resistant depression, but its effectiveness for bipolar depression is less certain. An updated systematic review and meta-analysis of 11 studies, including 7 in the meta-analysis, found that a single ketamine infusion significantly improved depression symptoms measured by the MADRS scale at 1 and 2 days. Non-randomized studies showed a 53% response rate at study endpoint. Response and remission rates were similar for single versus serial infusions. The rate of switching to mania was about 2.4%. Evidence for esketamine in bipolar depression remains limited and based on small, non-randomized studies.

Study at a glance

Abstract

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments. A total of 2657 articles were screened; 11 studies were included in the systematic review of which 7 studies were included in the meta-analysis (five non-randomized, N = 159; two RCTs, N = 33) with a mean age of 42.58 ± 13.1 years and 54.5% females. Pooled analysis from two RCTs showed a significant improvement in depression symptoms measured with MADRS after receiving a single infusion of ketamine (1-day WMD = −11.07; and 2 days WMD = −12.03). Non-randomized studies showed significant response (53%, p p < 0.001) at the study endpoint. The response (54% vs. 55%) and remission (30% vs. 40%) rates for single versus serial ketamine infusion studies were similar. The affective switch rate in the included studies approximated 2.4%. Esketamine data for bipolar depression are limited, based on non-randomized, small sample-sized studies. Further studies with larger sample sizes are required to strengthen the evidence.