Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms in Patients with Treatment-Resistant Depression: A Longitudinal Study
Matteo Leonardi, Alice Frediani, Mauro Angeletti, Monica Biseo, Giada Versaci, Michele Castiglioni, Miriam Olivola, Matteo Vismara, Alberto Varinelli, Monica Bosi, B. Benatti, N. Brondino, Bernardo Maria Dell’osso
Journal of Clinical Medicine December 29, 2025 DOI: 10.3390/jcm15010250 via OpenAlex
Summary
AI-generated from the abstractIntranasal esketamine rapidly reduces suicidal ideation and depressive symptoms in patients with treatment-resistant depression. Suicidal ideation scores dropped from 1.56 at baseline to 0.78 after one week and to 0.12 after six months. Depressive symptoms improved from a mean Montgomery-Åsberg Depression Rating Scale score of 30.9 at baseline to 17.5 after one week and 9.8 after six months. Male gender was a negative predictor of response; no other baseline variable predicted outcomes. The findings suggest intranasal esketamine is effective for rapid reduction and resolution of suicidal ideation in this population, and gender differences should be considered in treatment planning.
Study at a glance
| Characteristics | Longitudinal study Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Patients with treatment-resistant depression |
| Intervention | Intranasal Esketamine |
| Duration | 6-month follow-up |
| Topics | Depression |
| Keywords | Suicidal ideation Depression economics Rating scale Longitudinal study Depressive symptoms |
| Key finding | Intranasal esketamine rapidly reduces suicidal ideation and depressive symptoms in patients with treatment-resistant depression, with male gender as a negative predictor of response. |
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.