A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.
Sarah K. Fineberg, Esther Y Choi, Rosa Shapiro-Thompson, Khushwant Dhaliwal, Eli Neustadter, Madison Sakheim, Kaylee Null, Daniel Trujillo-Diaz, Jocelyne Rondeau, Giana F Pittaro, Jessica R. Peters, Philip R. Corlett, John H. Krystal
Neuropsychopharmacology June 2023 DOI: 10.1038/s41386-023-01540-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Pilot study Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Adults with borderline personality disorder |
| Interventions | Ketamine Midazolam |
| Dose | ketamine 0.5 mg/kg; midazolam 0.04 mg/kg |
| Duration | Single infusion; follow-up to Day 14 |
| Topics | Esketamine Ketamine |
| Key findings | A single ketamine infusion (0.5 mg/kg) was well tolerated but did not significantly reduce suicidal ideation, depression, anxiety, or BPD symptoms compared with midazolam. Ketamine produced greater improvement in socio-occupational functioning at Day 14, and this improvement correlated with depression improvement in the ketamine group but not the midazolam group. The authors argue these pilot results support further study of antidepressant-dosed ketamine in BPD. |
Abstract
This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 22
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Psychiatric risks for worsened mental health after psychedelic use. Journal of Psychopharmacology March 4, 2024
- Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder. Psychiatry Research March 5, 2023
- Anti-Suicidal Effects of Lithium, Ketamine, and Clozapine-A 10-Year Systematic Review. Pharmaceuticals May 18, 2025
- Efficacy of single and repeated ketamine administration for suicidal ideation in adults with psychiatric disorders: A meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
and 17 more in the library
Cites 14
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
and 9 more in the library