Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm.

Abstract

<h4>Background</h4>Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited.<h4>Methods</h4>In this multicentre prospective observational study, 90 outpatients with TRD received intranasal esketamine and were followed for 6 months across five timepoints (baseline, 2 weeks, 1 month, 3 months, 6 months). Forty-five participants had comorbid BPD and 45 had no personality disorder. Suicidal ideation and behavior were assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS; yes/no), self-harm with the Deliberate Self-Harm Inventory (DSHI; types and episode frequency), and trait impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11). Longitudinal changes were tested using Friedman analyses and Bonferroni-adjusted Wilcoxon post hoc tests, while associations were examined using Spearman correlations. Exploratory post hoc analyses also summarized recorded esketamine dose at scheduled follow-up visits and reconstructed lower- and upper-bound cumulative 6-month exposure under label-concordant assumptions.<h4>Results</h4>Suicidal ideation, suicidal behavior, and deliberate self-harm (types and episode frequency) decreased over time (all p < 0.001), with significant reductions from baseline evident from month 1 onwards. Self-harm episode frequency showed a marked decrease in the BPD group (mean 30.8 at baseline to 2.4 at six months). Baseline impulsivity was correlated with self-harm and suicidal indices, but these associations were less pronounced at six months. Recorded dose at T1-T4 and reconstructed cumulative 6-month exposure did not differ by BPD status; under both lower- and upper-bound exposure scenarios, cumulative dose was not significantly associated with change in C-SSRS or DSHI outcomes. No serious adverse events, treatment discontinuations, or increases in suicidality were observed.<h4>Conclusions</h4>In routine clinical care, intranasal esketamine was associated with sustained reductions, with significant improvement evident from month 1 onwards in suicidal ideation, suicidal behavior, and self-harm in TRD, including patients with comorbid BPD. Controlled studies are needed to confirm the durability of these findings, particularly in patients with comorbid BPD.

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