Profiling intranasal esketamine for adults with major depressive disorder and acute suicidal ideation or behavior: a phenotype-informed drug profile

Acute suicidal ideation in major depressive disorder (MDD) is a psychiatric emergency requiring rapid risk assessment, containment, and treatment. Conventional monoaminergic antidepressants have delayed onset, leaving an interval during which severe depressive distress persists. Intranasal esketamine, a rapid-acting N-methyl-D-aspartate receptor antagonist, is approved for MDD with acute suicidal ideation or behavior in the United States and for rapid reduction of depressive symptoms constituting a psychiatric emergency in Europe.

This Drug Profile reviews the pharmacology, pharmacokinetics, efficacy, safety, and regulatory positioning of intranasal esketamine, with attention to heterogeneity in suicidal presentations. Literature was identified through targeted PubMed/MEDLINE and Embase searches from inception to February 2026, supplemented by regulatory documents and reference-list hand-searching.

The pivotal ASPIRE trials showed rapid improvement in depressive symptom burden but no significant separation from placebo on the suicidality-specific CGI-SS-r endpoint. Reductions in hopelessness, psychological pain, or cognitive constriction are plausible but unproven as phenotype-specific effects. Esketamine should be used within its regulatory indication as one component of supervised, multimodal emergency care. The phenotype framework proposed here is hypothetical, intended to generate prospective research questions, and not a validated basis for individual treatment selection.