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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.