Intranasal esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A multicenter real-world longitudinal study.
Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi, Nicolaja Girone, Monica Macellaro, Giovanni Martinotti, Bernardo Dell'osso, Vassilis Martiadis, Miriam Olivola
Psychiatry research June 16, 2026 Peer reviewed DOI: 10.1016/j.psychres.2026.117288 via PubMed
Summary
In patients with treatment-resistant depression, those with comorbid borderline personality disorder experienced faster early improvement when treated with intranasal esketamine. Over six months, 53.3% achieved remission, with no significant difference between groups. However, response rates were higher in the borderline group starting from one month onwards. Overall, anxiety and impulsivity decreased, and cognitive function remained stable, indicating cognitive safety during treatment.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 90 |
| Population | treatment-resistant depression outpatients with and without borderline personality disorder |
| Key finding | Comorbid borderline personality disorder did not affect remission outcomes in treatment-resistant depression patients receiving intranasal esketamine. |
Abstract
Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without any personality disorder. The primary outcome was the trajectory of depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline (T0) to 2 weeks (T1), 1 month (T2), 3 months (T3) and 6 months (T4). A response was defined as a ≥ 50% reduction in MADRS score, and remission as a MADRS score of ≤10 at T4. Secondary outcomes (exploratory) included anxiety (HAM-A), impulsivity (BIS-11) and cognitive function (MoCA). MADRS scores decreased over time (F(2.45, 215.50)=365.10, p < 0.001, ηp²=0.81), with a significant time × BPD interaction (F(2.45, 215.50)=17.31, p < 0.001), indicating faster early improvement in the BPD group. Remission at six months was 53.3%, with no difference by BPD status (48.9%vs. 57.8%, p = 0.398). However, response rates were higher in the BPD group from month one onwards (T4 OR=12.57, p = 0.004). Sensitivity analyses adjusting for baseline psychotherapy/medications and excluding patients with a history of hypomanic episodes yielded consistent results. Across the whole sample, anxiety and impulsivity decreased, and there was no evidence of worsening of the MoCA score over six months, supporting cognitive safety. No serious adverse events occurred and no patients dropped out. In routine care, intranasal esketamine was associated with sustained improvement in TRD over six months, and comorbid BPD did not affect remission outcomes.