Esketamine nasal spray in hard-to-treat depression, with and without borderline personality disorder

The question

Does having borderline personality disorder alongside treatment-resistant depression change how well intranasal esketamine works in routine clinical care?

What they did

Researchers followed 90 outpatients with treatment-resistant depression who began intranasal esketamine at four Italian centres between 1 September 2024 and 30 September 2025. Half (45) also had borderline personality disorder and half (45) had no personality disorder. Depression was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) at the start and again at 2 weeks, 1 month, 3 months and 6 months. Anxiety, impulsivity and a brief cognitive test (MoCA) were tracked as secondary measures.

What they found

Depression scores fell significantly over time across the whole group (p < 0.001). At six months, 53.3% of patients were in remission (a MADRS score of 10 or less), with no significant difference between those with and without borderline personality disorder (48.9% vs 57.8%, p = 0.398). Response (at least a 50% drop in MADRS) was more common in the borderline group from one month onward (odds ratio 12.57 at six months, p = 0.004). Anxiety and impulsivity scores decreased across the sample, cognitive test scores did not worsen, no serious adverse events were reported and no patients dropped out.

The fine print

This was an observational study without a placebo or comparison treatment, so improvement over time cannot be separated from natural recovery, other care or expectation effects. The sample was small (90 people at four centres in one country) and participants were not randomly assigned to groups. Follow-up stopped at six months, secondary outcomes were labelled exploratory by the authors, and this summary is based on the abstract only.

What it means

In routine care, people with treatment-resistant depression improved over six months on intranasal esketamine, and having a co-occurring borderline personality diagnosis was not linked to worse remission rates — but without a control group these results cannot show that esketamine caused the improvement.

Evidence grade: Low. A real-world observational study with no control or placebo group and non-random assignment, so improvement cannot be attributed to the drug alone.

This summary is based on the study’s published abstract.