Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms in Patients with Treatment-Resistant Depression: A Longitudinal Study
Journal of Clinical Medicine – December 29, 2025
Source: OpenAlex
Summary
Intranasal Esketamine significantly reduces suicidal ideation (SI) in patients with treatment-resistant depression (TRD). In a study of 80 participants, SI scores dropped from an average of 1.56 to 0.12 within six months, and depressive symptoms decreased from 31.81 to 10.19. By one week, 68.4% of patients showed a response in SI, while overall MADRS response rates improved from 16.7% to 62.5% by six months. Notably, male gender negatively influenced early response rates, highlighting the need for tailored treatment approaches.
Abstract
Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatment-resistant depression (TRD), and the management of this condition should be as rapid and effective as possible. Intranasal Esketamine has shown promise in patients with TRD due to its rapid onset of action on both SI and depressive symptoms. Since this medication has been recently approved, real-world data on its efficacy remain scarce, and little is known about which patients are most likely to benefit from this approach. Aims: This study aimed (1) to evaluate the efficacy of intranasal Esketamine on SI and depressive symptoms and (2) to find potential predictors of clinical response. Methods: Patients with TRD who received intranasal Esketamine were included in this study. Clinical evaluations and psychometric assessments were made at baseline (T0) and at five subsequent time points (one week [T1], one month [T2], two months [T3], three months [T4], and six months [T5]). SI was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Furthermore, sociodemographic, clinical, and pharmacological data were collected. Results: Eighty patients diagnosed with TRD were enrolled. Suicidal ideation (C-SSRS items 1-5) decreased from 1.56 ± 1.65 at baseline to 0.78 ± 1.28 at T1 and 0.12 ± 0.52 at T5 (all p p p = 0.031); no other baseline variable was significant as a predictor. Conclusions: Intranasal Esketamine has been shown to be effective in the rapid reduction and lysis of SI in patients with TRD. Male gender was found as a negative predictor of response, suggesting the importance of considering gender differences during treatment planning.