Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm.
Fabiola Raffone, Filippo Mazzoni, Arianna De Ciechi, Nicolaja Girone, Monica Macellaro, Giovanni Martinotti, Bernardo Dell'Osso, Miriam Olivola, Vassilis Martiadis
Asian Journal of Psychiatry June 1, 2026 DOI: 10.1016/j.ajp.2026.104983 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Multicentre prospective observational study Longitudinal Peer reviewed |
|---|---|
| Sample size | 90 |
| Population | Outpatients with treatment-resistant depression, 45 with comorbid borderline personality disorder and 45 without personality disorder |
| Intervention | intranasal esketamine |
| Duration | 6-month follow-up with assessments at baseline, 2 weeks, 1 month, 3 months, and 6 months |
| Topics | Depression Esketamine |
| Keywords | Borderline personality disorder Self-harm Suicidal ideation Suicide |
| Citations | 3 |
| Key findings | Intranasal esketamine was associated with sustained reductions in suicidal ideation, suicidal behavior, and self-harm in treatment-resistant depression, including patients with comorbid borderline personality disorder. |
Abstract
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. 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. 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. 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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 5
- Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study Frontiers in Psychiatry July 9, 2026
- Beyond symptom reduction: Intranasal esketamine is associated with improved quality of life in treatment-resistant depression. Journal of Psychiatric Research September 7, 2026
- Esketamine Use and Attempted Suicide or Intentional Self-Harm Among Individuals with Treatment-Resistant Depression: A Retrospective Cohort Study. Drug safety September 2, 2026
- Esketamine-based treatment, depression-specific metacognitive training, and their combination in treatment-resistant depression: 6-month trajectories of depressive symptoms and rumination in a multicenter observational study. European Archives of Psychiatry and Clinical Neuroscience August 29, 2026
- Suicidal ideation covaries with depressive severity during six-month real-world esketamine treatment in a cohort enriched for borderline personality disorder. Journal of Affective Disorders August 20, 2026
Cites 20
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
and 15 more in the library