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The urgent need for appropriate treatment for suicide, the tenth leading cause of death, has led to numerous studies. This study aims to systematically identify and appraise systematic reviews with or without meta-analyses investigating ketamine in suicidal ideation and behaviours. Scopus, ISI, Embase, PubMed, CINAHL, PsycINFO, Cochrane Library, Google Scholar and two registries were searched without any restrictions for systematic reviews investigating the efficacy of ketamine on suicidal ideation and behaviours. The primary outcome was the final inference of ketamine effectiveness. A formal narrative synthesis was conducted, and the AMSTAR-2 tool was used to evaluate the quality of the studies. Of 27 studies that addressed ketamine for suicidal ideation, only four reported mixed or negative results, and out of nine reviews, esketamine was significantly beneficial only in five. A transient rise in pulse rate and blood pressure, dissociation, confusion, blurred vision, nausea and vertigo were the most common adverse effects; however, most were mild. More than two-thirds of the included studies qualified as of low or critically low quality. Preliminary evidence for the short-term efficacy of ketamine in suicidality was noted by the majority of reviews; however, long-term effects remained unknown. Due to the low quality of many studies and the limitations of core studies, further research is required., (© 2022 British Pharmacological Society.)

Objective: Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. Method: The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Results: Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. Conclusion: The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression. [ABSTRACT FROM AUTHOR]