Intranasal Esketamine for Rapid Reduction of Suicidal Ideation in Treatment-Resistant Depression: A Narrative Review

Abstract

Background: Treatment-resistant depression is associated with persistent symptoms, impaired functioning, recurrent illness, and an increased burden of suicidal ideation. Conventional oral antidepressants may require several weeks to produce clinically meaningful improvement, creating a therapeutic challenge when severe depressive symptoms and suicidal thoughts require rapid stabilization. Intranasal esketamine has emerged as a supervised, rapidly acting intervention that modulates glutamatergic neurotransmission and is generally administered alongside an oral antidepressant and comprehensive psychiatric care. Objective: This narrative review examined the clinical role of intranasal esketamine in the early reduction of depressive symptoms and suicidal ideation, with particular attention to treatment-resistant depression, acute suicidal depressive episodes, sustainability of response, safety, and implementation. Methods: Relevant literature concerning intranasal esketamine, ketamine-related antidepressant mechanisms, treatment-resistant depression, and suicidality was reviewed and synthesized thematically. Evidence was organized around clinical populations, mechanisms of action, speed of response, suicidal-ideation outcomes, maintenance treatment, safety, and clinical implementation. Results: Available evidence indicates that intranasal esketamine can produce earlier improvement in depressive symptoms than conventional oral antidepressant treatment alone, particularly during the initial hours and days of supervised treatment. Reductions in selected suicidal-ideation measures have also been reported; however, improvement in suicidal thoughts does not establish prevention of suicide attempts or mortality. Interpretation is influenced by differences in populations, outcome instruments, comparator conditions, concomitant treatments, and follow-up durations. Dissociation, sedation, dizziness, nausea, perceptual disturbances, and transient elevations in blood pressure require structured monitoring. Conclusion: Intranasal esketamine represents a clinically relevant adjunctive option for selected adults with treatment-resistant depression or severe depressive episodes requiring rapid symptom reduction. Its use should remain integrated within comprehensive psychiatric management, while further research clarifies its specific effects on suicidal behaviour, long-term maintenance, comparative effectiveness, and accessibility