Background
There is an upward trend seen globally of more and more people acting upon suicidal thoughts and behaviours over the last 45 years (World Atlas, 2017). The latest World Health Organization (WHO) findings report that approximately 800,000 people die due to suicide every year, which is one person every 40 seconds and there are many more people who attempt a suicide (World Health Organization, 2017). Suicidal ideations (SI) or suicidal thoughts are prevalent among those that suffer from depression, mental illness or stressed-related trauma (Liu and Miller, 2014; Patelaros et al., 2015; Conejero et al., 2018). In general, these thoughts are temporary and can be treated, however they place the individual at risk of committing suicide (Burr et al., 2018). Therefore, they need to be taken seriously as a warning sign of possibly imminent death. The pharmacological and non-pharmacological treatments for SI, which have been used up to date, have demonstrated successful results by the literature in a long term (Griffiths et al. 2014). However, there is almost no treatment that can assist in providing an immediate relief for those patients (Mathew and Zarate, 2016). For the last 5 years, the dissociative anesthetic medication, Ketamine, has been studied as a potential short acting treatment for SI. Ketamine is currently used off-label as a treatment for refractory depression in ketamine infusion clinics worldwide (Kirby, 2015). However, the Food and Drug Administration, US (FDA) and the National Health Services, UK (NHS) have not yet approved its use as an anti-depressive and anti-suicidal agent (Zhang et al., 2016; Mathew and Zarate, 2016). If Ketamine demonstrates effectiveness for the treatment of SI, it can be considered as an easily available, cost-effective and fast-acting treatment of choice for these patients worldwide.
Objective
This systematic review aims to provide a complete and exhaustive summary of the available literature by identifying controlled trials that explore the efficacy of IV ketamine vs. no medication/ placebo in a short and long-term treatment option in adults who present with suicidal ideations.
Study Design
Systematic review
Methods
A comprehensive literature search was conducted to include all the available full-text controlled studies (published and non-published) written upon the subject. Databases like MedLine/PubMed, CINAHL, GHL WHO (Global Health Library by World Health Organisation), Google Scholar, National Institute of Health (NIH) Clinical Trials and WHO Trial registry were searched with no year of publication restriction. A MeSH structure and simple keywording were used in a variety of combinations to find relevant studies. The retrieved controlled studies, which were randomised-controlled studies only, meeting the inclusion criteria were included and their data were extracted to be critically appraised. The Cochrane RoB 2.0 Tool (The Risk of Bias Tool) for RCTs was used to assess the risk of bias of the included studies.
Results
The search strategy identified six published and one unpublished RCTs that were eligible for inclusion in this systematic review. Four of those studies compared ketamine to midazolam and three of them compared ketamine to saline administration intravenously. Although, the studies have used different SI scales in analyzing the risk of the population pre- and post-intervention and they have used different doses for the ketamine and for the controlled medication, all of them demonstrated a superior efficacy of ketamine to the controlled agent at a different follow-up period. This effect however subsided within the end of the follow-up period for each study. From the recruited studies, there is a number of methodological limitations, which given the serious flaws identified, the appropriateness of this conclusion should be considered with caution.
Conclusions
This systematic review has identified that there are no established guidelines in the treatment of suicidal ideations. This makes it difficult to analyse the efficacy of any SI intervention, including the intravenous ketamine administration. Ketamine suggests a potential benefit for treating emergent and chronic suicidality in a short-term, however even though the evidence-based research is growing, it is still not conclusive. Ketamine deserves consideration for use with certain patients as a temporizing measure until alternative methods or a multidisciplinary approach are implemented for SI treatment in adults.
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