New research provides evidence that ketamine therapy might be a suitable option for adults with borderline personality disorder and treatment-resistant depression. The new findings have been published in Psychiatry Research.
Ketamine therapy is a type of treatment for depression that involves the use of ketamine, an anesthetic drug that has been found to have antidepressant properties. The therapy typically involves a series of intravenous (IV) infusions of ketamine in a clinical setting, under the supervision of a trained healthcare provider.
Ketamine works differently than traditional antidepressant medications, which usually target serotonin or other neurotransmitters in the brain. Instead, ketamine acts on a different neurotransmitter called glutamate, which is involved in communication between brain cells.
Borderline personality disorder (BPD) is a mental health condition that affects how a person thinks, feels, and behaves. People with BPD often have difficulty regulating their emotions and experience intense mood swings, which can lead to impulsive behavior and strained relationships.
BPD often coexists with major depressive disorder. When BPD and depression are present together, the depression tends to be more severe and resistant to treatment. Even with available treatments like antidepressants and psychotherapy, people with BPD often have poorer outcomes than those without BPD. Unfortunately, there is currently no FDA-approved treatment specifically for depressed individuals with comorbid BPD.
“This analysis was directly inspired by my experience treating patients with depression with comorbid borderline personality,” said study author Joshua D. Rosenblat, a psychiatrist and the medical director of Braxia Health and an assistant professor at the University of Toronto.
“I have seen this population stigmatized and often people undertreat depression, assuming that all symptoms are being driven by the personality disorder. As I personally saw some incredibly positive results with IV ketamine in this group, I wanted to do a quantitative analysis to see if benefits and safety were comparable to those without personality disorders.”
“Of note, comorbid BPD is often an exclusion criterion in clinical trials which also was a reason why I think this question was particularly important as previous trials may or may not generalize to the group of treatment-resistant depression with comorbid BPD.”
The researchers studied 100 people who had received four doses of ketamine over two weeks at an outpatient clinic. Half of the people had both depression and BPD, and the other half only had depression.
The study looked at two main things: how the symptoms of borderline personality disorder changed, and if there was a difference in how depression symptoms changed between the group with borderline personality disorder and the group without it. The researchers also investigated thoughts of suicide, how anxious people felt, and how well they were able to function in daily life. Lastly, they checked how much people dissociated (felt disconnected from reality) after each dose of ketamine using a scale called the Clinician Administered Dissociative Symptom Scale.
The study found that patients who had depression and BPD experienced a significant improvement in their depression symptoms after receiving ketamine. The improvement was similar to that seen in patients with depression but without BPD. The severity of depression symptoms went from being classified as severe at the start of the study to moderate at the end of the treatment.
The study also found that patients who had borderline personality disorder experienced a significant improvement in their symptoms after receiving ketamine treatment. Symptoms went from being classified as high severity at the start of the study to moderate severity after the ketamine infusions.
“The most surprising part of the analysis was the reduction in symptoms of BPD,” Rosenblat said. “I was expecting depressive symptoms to improve, but I did not expect BPD symptoms to improve. BPD symptoms improved rapidly and robustly. This needs to be tested further but was pretty encouraging to see.”
The researchers also observed reductions in anxiety and suicidal ideation in both depressed patients with BPD and depressed patients without BPD, along with increases in functionality. The study found that both groups experienced only mild levels of dissociation during the treatment, and that by the final treatment, both groups had less dissociation than they did at the start.
Rosenblat told PsyPost that the “key point is that while depression with comorbid BPD is generally difficult to treat, IV ketamine was equally safe and effective for patients with or without BPD.”
“As such, I do not believe that the presence of comorbid BPD should be an exclusion criterion for treatment-resistant depression patients to receive IV ketamine. Of note, however, I am not suggesting that ketamine is a treatment for BPD, but that for patients with depression and BPD, it may still be a suitable treatment option if other options have failed.”
While the results are promising, randomized placebo-controlled studies are needed to verify the efficacy of ketamine treatment for those with depression and BPD. Ketamine therapy is not yet approved by the U.S. Food and Drug Administration for the treatment of depression, and it is considered an off-label use of the drug.
“Major caveat/limitation is that this was an uncontrolled open label observational study,” Rosenblat explained. “As such, we really need RCTs to determine the safety and efficacy of ketamine in this group. The long-term effects are also very important to evaluate. I also wonder about if we can combine ketamine with dialectical behavior therapy in this group and hope to study this question.”
The study, “Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder“, was authored by Kevork Danayan, Noah Chisamore, Nelson B. Rodrigues, Joshua D. Di Vincenzo, Shakila Meshkat, Zoe Doyle, Rodrigo Mansur, Lee Phan, Farhan Fancy, Edmond Chau, Aniqa Tabassum, Kevin Kratiuk, Anil Arekapudi, Kayla M. Teopiz, Roger S. McIntyre, and Joshua D. Rosenblat.