Esketamine and suicidal thoughts in treatment-resistant depression, with and without borderline PD

The question

Does nasal spray esketamine, used in routine clinical care, go along with fewer suicidal thoughts and less self-harm in people with hard-to-treat depression, including those who also have borderline personality disorder?

What they did

Researchers followed 90 outpatients with treatment-resistant depression (depression that has not responded to standard treatments) at several clinics. Forty-five also had borderline personality disorder, and 45 had no personality disorder. All received intranasal esketamine and were assessed five times over six months: at the start, 2 weeks, 1 month, 3 months and 6 months. Suicidal thoughts and behaviour, self-harm and impulsivity were measured with standard rating scales, and esketamine doses recorded at visits were also examined.

What they found

Suicidal thoughts, suicidal behaviour and self-harm all declined over the six months (all p < 0.001), with significant drops from the one-month mark onward. In the borderline personality disorder group, the average number of self-harm episodes fell from 30.8 at the start to 2.4 at six months. Impulsivity at the start was linked to self-harm and suicide-related measures, but these links were weaker by six months. Recorded doses and estimated total six-month exposure did not differ between the two groups, and total dose was not significantly linked to how much the suicide or self-harm scores changed. No serious adverse events, treatment discontinuations, or increases in suicidality were reported.

The fine print

There was no control group or placebo, so the improvements cannot be separated from the natural course of illness, other care people were receiving, or expectation effects. The sample was modest (90 people) and drawn from those already prescribed esketamine in clinical practice, which may not represent everyone with treatment-resistant depression. Suicidal ideation was recorded as yes/no and self-harm counts were self-reported, and part of the dose analysis relied on reconstructed estimates rather than complete records. This summary is based on the abstract only.

What it means

In routine care, people with hard-to-treat depression, including those with borderline personality disorder, reported fewer suicidal thoughts and less self-harm over six months of esketamine treatment, but without a comparison group it is not possible to say the drug caused the change.

Evidence grade: Low. A prospective observational study with no control or comparison group receiving another treatment, so improvement over time cannot be attributed to esketamine itself.

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