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Review
. 2023 Dec 2;13(12):1672.
doi: 10.3390/brainsci13121672.

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

Nicolas A Nunez  1   2 , Boney Joseph  3 , Rakesh Kumar  1 , Ioanna Douka  2 , Alessandro Miola  1   4 , Larry J Prokop  5 , Brian J Mickey  2 , Balwinder Singh  1
Affiliations
Review

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

Nicolas A Nunez et al. Brain Sci. .

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 < 0.001) and remission rates (38%, 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.

Keywords: ketamine; metanalysis; systematic review; treatment-resistant bipolar depression.

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Conflict of interest statement

Balwinder Singh received research grant support from Mayo Clinic, National Network of Depression Centers (NNDC), and BD2 (Breakthough Disoveries for thriving with Bipolar Disorder). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
(A) Forest plot of pooled response rates for open label studies; (B) forest plot of pooled remission rates for open-label studies [16,28,29,31,33].
Figure 3
Figure 3
(A) Forest plot of pooled response rates for randomized controlled trials and open-label studies; (B) forest plot of pooled remission rates for randomized controlled trials and open-label studies [16,26,27,28,29,31,33].
Figure 3
Figure 3
(A) Forest plot of pooled response rates for randomized controlled trials and open-label studies; (B) forest plot of pooled remission rates for randomized controlled trials and open-label studies [16,26,27,28,29,31,33].
Figure 4
Figure 4
(A) Forest plot of pooled response rates for single vs. serial infusions; (B) forest plot of pooled remission rates for single vs. serial infusions [16,26,27,28,29,31,33].
Figure 4
Figure 4
(A) Forest plot of pooled response rates for single vs. serial infusions; (B) forest plot of pooled remission rates for single vs. serial infusions [16,26,27,28,29,31,33].
See this image and copyright information in PMC

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