2026 ECNP Congress

PS02-2112

Deliberate self-harm and impulsivity trajectories during intranasal esketamine in borderline personality disorder comorbid with treatment-resistant depression

Fabiola Raffone — F. Mazzoni, A. De Ciechi, N. Girone, M. Macellaro, G. Martinotti, B. Dell'Osso, M. Olivola, V. Martiadis · University of Study L. Vanvitelli- Asl Napoli 1 Centro, Department of Psychiatry- Department of Mental Health, Naples, Italy

2026 ECNP Congress

Introduction

Borderline personality disorder (BPD) is a significant factor in chronic self-harm and suicide-related risk. The co-occurrence of BPD and treatment-resistant depression (TRD) is associated with an increased risk of suicide and a reduced response to standard antidepressants [1, 2]. Patients with BPD have been underrepresented in pivotal esketamine trials, and longitudinal data on self-harm and trait impulsivity during esketamine treatment in this subgroup are scarce [3, 4].

Aims

This study aims to characterise six-month trajectories of deliberate self-harm, suicidal ideation, suicidal behaviour and trait impulsivity in patients with TRD and comorbid BPD receiving intranasal esketamine. The study also aims to assess whether the BPD subgroup shows a distinct pattern.

Methods

This was a prospective observational study across four Italian community mental health services. Ninety outpatients (aged 18–65) with a current major depressive episode and TRD (non-response to at least two antidepressant trials) were enrolled between September 2024 and September 2025: 45 with comorbid BPD and 45 without any personality disorder. Intranasal esketamine (56/84 mg) was administered with oral antidepressants maintained. Assessments were conducted at baseline (T0), after two weeks (T1), one month (T2), three months (T3) and six months (T4). The following scales were used: the Columbia-Suicide Severity Rating Scale (C-SSRS), the Deliberate Self-Harm Inventory (DSHI) and the Barratt Impulsiveness Scale-11 (BIS-11). Change was tested using a Friedman ANOVA and Bonferroni-adjusted Wilcoxon post hoc tests. Spearman correlations were used to link impulsivity to risk indices. Cumulative exposure was reconstructed under label-concordant lower- and upper-bound scenarios.

Results

Patients with BPD were younger (mean age: 38.8 vs. 50.7 years), more often female (75.6% vs. 48.9%), and had made more suicide attempts in their lifetime (mean: 0.73 vs. 0.07). Baseline BIS-11 scores were higher (attentional: 23.5 vs. 17.6; motor: 31.2 vs. 19.5; non-planning: 33.7 vs. 24.8; all p < 0.001). In the BPD subgroup, the mean frequency of DSHI episodes fell from 30.8 to 34.1 (T1), 25.2 (T2), 16.4 (T3) and 2.4 (T4) (Friedman chi-square (4) = 171.98, p < 0.001; Kendall’s W = 0.51; baseline-to-T4 r = 0.82). The comparator group showed consistently low values. In the full cohort, suicidal ideation and behaviour (C-SSRS) also declined (χ²(4) = 116.20 and 43.46, both p < 0.001), with significant reductions from the first month onwards. Baseline BIS-11 subscales correlated moderately to strongly with DSHI indices (rho = 0.60–0.70). These correlations weakened considerably by T4, consistent with the idea that impulsivity and self-injurious behaviour are becoming less closely linked. Reconstructed cumulative dose did not differ by BPD status and was not associated with change in any outcome. Adverse events occurred in 24.4% of patients (nausea in 7.8% and dizziness in 4.4%), but there were no serious events, discontinuations or suicide attempts.

Conclusions

In routine care, patients with TRD and comorbid BPD showed sustained reductions in deliberate self-harm over six months of intranasal esketamine. There was attenuation of the impulsivity-self-harm association and no iatrogenic worsening. These findings support the cautious inclusion of BPD patients in esketamine treatment programmes as an adjunct to integrated care. However, the observational design and heterogeneous background treatments limit generalizability.

References

References

  1. Hawton K, Casañas i Comabella C, Haw C, Saunders K, 2013. Risk factors for suicide in individuals with depression: a systematic review. J Affect Disord 147(1–3), 17–28.
  2. Yen S, Peters JR, Nishar S, et al., 2021. Association of borderline personality disorder criteria with prospectively observed suicide attempts. JAMA Psychiatry 78(2), 187–194.
  3. Martinotti G, d’Andrea G, Di Nicola M, et al., 2022. Real-world experience of esketamine use to manage treatment-resistant depression: a multicentric study on safety and effectiveness (REAL-ESK study). J Affect Disord 319, 646–654.
  4. Fiorillo A, Demyttenaere K, Martiadis V, Martinotti G, 2025. Treatment-resistant depression: from clinical burden to precision therapeutics. Front Psychiatry 16, 1588902.