{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:55:56Z","timestamp":1793336156206,"version":"4.5.0"},"reference-count":74,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"\n Importance<\/jats:title>\n While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs).<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, PsycInfo, Cochrane Library, and Embase were systematically searched from database inception through November 7, 2025, with no language limits.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials (RCTs) with (1) diagnosis of an MDE; (2) intervention and comparator groups consisting of intravenous ketamine and controls (eg, saline or midazolam); and (3) suicidal and depressive symptoms as efficacy outcomes were included.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n \n Hedges\n g<\/jats:italic>\n standardized mean differences (SMDs) were used to analyze improvement in suicidal and depressive symptoms using random-effects models. Multiple subgroup analyses were also conducted.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcomes included the following: (1) changes in suicidal and depressive symptoms; (2) response and remission rates of depressive symptoms; and (3) safety measures (eg, adverse events and serious adverse events).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 26 RCTs comprising 1166 patients with an MDE (n\u2009=\u2009626 receiving ketamine and n\u2009=\u2009540 as control patients) were included. For suicidal symptoms, patients receiving a single ketamine infusion, compared with control patients, had significantly lower symptoms at 24 hours (SMD, \u22120.69 [95% CI, \u22120.98 to \u22120.40]) and at 1 month (SMD, \u22120.70 [95% CI, \u22121.17 to \u22120.24]). Those with repeated ketamine infusions showed a similar reduction of suicidal symptoms at the end of the treatment (SMD, \u22120.72 [95% CI, \u22121.00 to \u22120.43]). For depressive symptoms, significant reductions were shown at 4 hours (SMD, \u22121.74 [95% CI, \u22122.43 to \u22121.06]), 24 hours (SMD, \u22121.15 [95% CI, \u22121.58 to \u22120.72]), 3 days (SMD, \u22120.97 [95% CI, \u22121.73 to \u22120.20]), and 1 week (SMD, \u22120.89 [95% CI, \u22121.65 to \u22120.13]) after a single ketamine infusion and at the end of the treatment after repeated infusions (SMD, \u22120.81 [95% CI, \u22121.16 to \u22120.46]). Reported serious adverse events (eg, hospitalizations and deaths) were unrelated to the interventions, and other adverse events (eg, headache) were transient and resolved during the trials.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The findings of this systematic review and meta-analysis suggest that single and repeated intravenous ketamine infusions are efficacious in reducing suicidal and depressive symptoms in patients with an MDE in the acute phase, while longer-term outcomes are not well established.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2026.0612","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:31:33Z","timestamp":1778081493000},"page":"714","source":"Crossref","is-referenced-by-count":7,"title":["Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode"],"prefix":"10.1001","volume":"83","author":[{"given":"Sung 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