Ketamine for suicidality: an umbrella review

Introduction

Suicide remains a major public‑health problem despite global declines in rates; it was the tenth leading cause of death overall and the second leading cause among people in their second and third decades of life. Multiple biological and psychosocial mechanisms have been proposed to underlie suicidal ideation and behaviours, including monoamine dysregulation, altered cortisol and stress responses, neurotrophic and glutamatergic dysfunction, inflammation and other systemic factors. Ketamine, a glutamate receptor modulator, has attracted attention because preclinical and clinical studies report rapid antidepressant and putative antisuicidal effects, and several mechanistic hypotheses (effects on glutamate neurotransmission, inflammation, neurotrophic signalling, sleep and reward systems) have been advanced to explain its actions. Shamabadi and colleagues set out to perform an umbrella review: a systematic identification, collation and methodological appraisal of existing systematic reviews and meta‑analyses that investigated ketamine (including racemic ketamine and the S‑enantiomer esketamine) for suicidal ideation and suicidal behaviours in humans. The authors searched multiple bibliographic databases (Scopus, ISI, Embase, PubMed, CINAHL, PsycINFO, Cochrane Library), Google Scholar, two review registries (PROSPERO and the Research Registry), and additional sources including expert contact and web searches, with no language restriction, aiming to capture reviews that explicitly used ketamine and suicid* in title/abstract/keywords and that included at least two human core studies addressing suicidality.