{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:52:27Z","timestamp":1784325147014,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>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 \u00b1 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 = \u221211.07; and 2 days WMD = \u221212.03). Non-randomized studies showed significant response (53%, p &lt; 0.001) and remission rates (38%, p &lt; 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.<\/jats:p>","DOI":"10.3390\/brainsci13121672","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T13:45:41Z","timestamp":1701524741000},"page":"1672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An Update on the Efficacy of Single and Serial Intravenous Ketamine Infusions and Esketamine for Bipolar Depression: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"given":"Nicolas A.","family":"Nunez","sequence":"first","affiliation":[{"name":"Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA"},{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-9344","authenticated-orcid":false,"given":"Boney","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3916-9263","authenticated-orcid":false,"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Douka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Miola","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA"},{"name":"Department of Neuroscience (DNS), University of Padova, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry J.","family":"Prokop","sequence":"additional","affiliation":[{"name":"Mayo Medical Libraries, Mayo Clinic College of Medicine, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Mickey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7062-8192","authenticated-orcid":false,"given":"Balwinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,2]]},"reference":[{"key":"ref_1","first-page":"685","article-title":"The prevalence, clinical relevance, and public health significance of subthreshold depressions","volume":"25","author":"Judd","year":"2002","journal-title":"Psychiatr. 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