Exciting early results in borderline personality disorder (BPD) research! A pilot randomized trial that its authors described as the first of ketamine in BPD reported that infusions were well tolerated and that social and work functioning improved more than with a comparison drug; a psilocybin pilot reported depression scores falling from 28.56 to 17.22 (Cohen's d = 1.41); a study of 100 people with treatment-resistant depression found ketamine recipients with comorbid BPD had significant reductions in depression, borderline symptoms, suicidality and anxiety; and a six-month esketamine study reported mean self-harm episodes in the BPD group falling from 30.8 to 2.4. Encouraging to see careful research bringing such promising results for people living with BPD.
Key studies
Study 1. Ketamine in 22 adults with borderline personality disorder (Fineberg, 2023)
A pilot randomized trial that its authors called the first of ketamine in BPD found greater social and work functioning gains than the comparison drug at day 14!
In a double-blind randomized pilot trial of 22 adults with BPD, which the authors described as the first randomized controlled trial of ketamine in BPD, researchers reported that social and work (socio-occupational) functioning improved more with ketamine (10 people) than with the active comparison drug midazolam (12 people) at day 14 (p = 0.03). Infusions were well tolerated in both groups, and the authors saw reason for optimism that ketamine will be well tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments!
“This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD.”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Fineberg SK, Choi EY, Shapiro-Thompson R, et al. A pilot randomized controlled trial of ketamine in Borderline Personality Disorder. Neuropsychopharmacology. 2023;48(7):991-999. https://doi.org/10.1038/s41386-023-01540-4
Study 2. Psilocybin in 9 adults with borderline personality disorder and depression (Grant, 2026)
Depression scores fell from 28.56 to 17.22 after a single psilocybin session in people with BPD (Cohen's d = 1.41)!
In an open-label pilot study of nine adults with both BPD and major depressive disorder (MDD), researchers reported statistically significant improvement in depression symptom scores after a single psilocybin session (mean score 28.56 at baseline to 17.22 at the final visit; Cohen's d = 1.41, P = 0.003). Assessments took place before dosing, on the dosing day and at 1, 2 and 4 weeks afterward, and the researchers concluded that BPD does not appear to interfere with response to depressive symptoms!
“This small open-label study resulted in statistically significant improvement in MDD symptoms”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Grant JE, Boutouis S, O'Brien M, et al. An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder. Clin Neuropharmacol. 2026;49(4):163-169. https://doi.org/10.1097/wnf.0000000000000683
Study 3. Repeated ketamine infusions in 100 people with treatment-resistant depression, half with borderline personality disorder (Danayan, 2023)
Ketamine brought significant reductions in depression, borderline symptoms, suicidality and anxiety in people with treatment-resistant depression and BPD, with large effect sizes!
In a retrospective analysis of real-world care at the Canadian Rapid Treatment Centre of Excellence, researchers compared 100 people with treatment-resistant depression, 50 with comorbid BPD and 50 without, who received repeated intravenous ketamine infusions over two weeks, and reported that both groups improved significantly on depression, suicide ideation, anxiety and functionality scales with large effect sizes, and the benefit was similar in both groups. The BPD group had a significant 5.95-point reduction in depression (QIDS-SR 16) scores and a significant 0.64 reduction in borderline symptom (BSL-23) scores, and the authors concluded that ketamine recipients with comorbid BPD exhibited a significant reduction in symptoms of depression, borderline personality, suicidality and anxiety!
“Patients with TRD and comorbid BPD receiving ketamine exhibited a significant reduction in symptoms of depression, borderline personality, suicidality, and anxiety.”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Danayan K, Chisamore N, Rodrigues NB, et al. Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder. Psychiatry Res. 2023;323:115133. https://doi.org/10.1016/j.psychres.2023.115133
Study 4. Esketamine in 90 adults with hard-to-treat depression, half with borderline personality disorder (Raffone, 2026)
Self-harm episodes in people with BPD fell from 30.8 to 2.4 at six months with esketamine, with significant reductions from month 1!
In a six-month multicentre observational study of 90 outpatients with treatment-resistant depression receiving intranasal esketamine (45 with comorbid BPD, 45 with no personality disorder), researchers reported that suicidal ideation, suicidal behavior and deliberate self-harm all decreased over time (p < 0.001), with significant reductions evident from month 1 onwards. In the BPD group, mean self-harm episodes fell from 30.8 at baseline to 2.4 at six months, and no increases in suicidality were observed!
“Self-harm episode frequency showed a marked decrease in the BPD group (mean 30.8 at baseline to 2.4 at six months).”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Raffone F, Mazzoni F, De Ciechi A, et al. Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm. Asian J Psychiatr. 2026;120:104983. https://doi.org/10.1016/j.ajp.2026.104983
Related reading
- Artna E, Sandhu G, Chisamore N, et al. Psychedelics as a potential treatment for borderline personality disorder: A narrative review. Psychiatry Res. 2026;361:117152. https://doi.org/10.1016/j.psychres.2026.117152 — A narrative review of 22 studies (ketamine, esketamine and psilocybin) reporting preliminary evidence that these treatments may improve core BPD symptoms and socio-occupational functioning.
- Scott E, Thekkuden DT, Kerr K, et al. Ketamine/esketamine in the treatment of depression with comorbid borderline personality disorder or traits: A systematic review of effectiveness. Aust N Z J Psychiatry. 2025;59(12):1046-1058. https://doi.org/10.1177/00048674251374472 — A systematic review of nine studies (n = 281) finding that patients with depression and comorbid BPD were equally likely to respond to ketamine/esketamine as those without BPD.
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This page summarizes published research for education only. It is not medical advice. Any change to a medication remains the decision of that person’s own prescriber.
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