# Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms in Patients with Treatment-Resistant Depression: A Longitudinal Study

## TL;DR

Intranasal Esketamine rapidly reduces suicidal thoughts and depressive symptoms in patients with treatment-resistant depression, with male gender predicting slower response.

## Contribution

This study provides real-world evidence on the effectiveness of intranasal Esketamine and identifies male sex as a potential predictor of slower response.

## Key findings

- Suicidal ideation decreased significantly from baseline to six months after treatment with intranasal Esketamine.
- Depressive symptoms, as measured by MADRS, showed a substantial reduction over the six-month period.
- Male patients had lower odds of early response to Esketamine, indicating gender differences in treatment outcomes.

## 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 < 0.001). MADRS fell from 31.81 ± 7.94 to 23.62 ± 9.08 and 10.19 ± 7.33 at the same time points (all p < 0.001). By T1, 68.4% achieved an SI response on the C-SSRS. The MADRS response rate increased from 16.7% at T1 to an overall response of 62.5% at T5. Male sex predicted lower odds of early response on the C-SSRS (OR = 0.21, 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.