Ketamine and Esketamine in Acute Suicidal Presentations: Evidence, Limits, and a Conceptual Recovery-Enabling Downstaging Framework.

Abstract

Objective: To synthesize evidence for intravenous racemic ketamine and regulated intranasal esketamine in adults with acute suicidal presentations; distinguish the outcomes these interventions have and have not been shown to change; and place any rapid response within a complete emergency suicide-care pathway.

Methods: A narrative review of PubMed/MEDLINE-indexed literature was updated through July 16, 2026. Searches and study selection were performed by Wiesław Jerzy Cubała and Anita Słupska. Priority was given to randomized trials, systematic reviews and meta-analyses, pivotal ASPIRE publications, current US and European product information, and studies of emergency-department safety planning, lethal-means counseling, and post-discharge care. No formal risk-of-bias assessment or pooled reanalysis was undertaken.

Results: Intravenous racemic ketamine has randomized and meta-analytic evidence for rapid, short-term reduction of suicidal ideation in selected adults, with important variation by population, comparator, measure, and follow-up. The evidence does not establish prevention of suicide attempts or deaths. In ASPIRE I and II, regulated intranasal esketamine added to hospitalization, a newly initiated or optimized oral antidepressant, and comprehensive standard care accelerated improvement in depressive symptoms; clinician-rated suicidality improved markedly in both groups and did not consistently separate from placebo plus standard care. Across both evidence streams, a post-dose score cannot substitute for dynamic risk formulation, level-of-care decisions, safety planning, lethal-means restriction, or a confirmed transition of care.

Conclusions: Intravenous racemic ketamine may produce a rapid, short-term reduction in suicidal ideation in selected adults, whereas regulated intranasal esketamine has demonstrated accelerated improvement in depressive symptoms in hospitalized patients with major depressive disorder and acute suicidal ideation with intent, without a consistent treatment-specific effect on suicidality. Neither intervention has been shown to prevent suicide attempts or deaths. We propose a conceptual, non-validated recovery-enabling downstaging framework to describe a time-limited movement from high acuity toward a state in which collaboration and definitive treatment become more feasible. The framework is intended to complement, not replace, dynamic risk formulation, safety planning, and disposition assessment.