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Here’s a new article—a randomized trial regarding treatment of borderline personality disorder. Is there a new option? Perhaps, but you’ll want to see the details.
Hi! Jim Phelps here for the Psychopharmacology Institute. Let’s begin by reminding ourselves of the treatments that have recognized efficacy for people with borderlinity, my preferred term instead of the still somewhat pejorative and dangerously categorical “yes or no” borderline personality disorder. You may remember the 2006 randomized trial of dialectic behavior therapy led by Marsha Linehan that was a watershed moment. Finally, there was a reason to invoke the label of borderline personality disorder. It became a required ticket to receive the only treatment with randomized trial evidence for efficacy. And by now, there are actually at least 3 psychotherapies with such evidence, but there aren’t enough therapists with specialty training and even fewer who are willing to make borderlinity their main practice focus.
In an important review, the experienced borderline researcher John Gunderson demonstrated that therapists who have no specific training in these techniques can achieve results not far short of the specialized therapies. He concludes that mental health professionals, especially psychiatrists, should “embrace the challenges that these patients undeniably pose. Only by doing this can the mental health profession begin to address the public health needs of these patients.” According to his review, the mental health professional establishes a treatment relationship just as they do for other patients but adds support from colleagues and increased attention to safety planning and clear treatment goals. Now, if we had a medication that was clearly superior to placebo, we could enter that treatment relationship with even more to offer.
So, here’s a new randomized trial of brexpiprazole for borderline personality disorder. The first step in evaluating a new randomized trial, is there a pharmaceutical company behind this? Only somewhat. The investigators initiated this study, not a pharmaceutical company, and they don’t seem to have major financial or other connections to the company other than research grants to the lead author. Next, is the study large enough? Well, recruiting a group of 80 patients with this diagnosis and getting 70% of them all the way through an 8-week trial is an achievement onto itself.
The results are a bit odd, as the authors are first to point out. There was no separation between brexpiprazole and placebo until the last week. In the first 2 weeks, there was a huge drop in borderlinity rating scores using the well-established Zanarini scale, but that drop was almost identical in the placebo group. So, one reason why brexpiprazole did not demonstrate superiority is because placebo worked so well until the last week, when a 5-point difference emerges. That’s one-third of the patients’ starting scores on the Zanarini scale.
The authors offer several thoughtful explanations for this last-week difference but overall seemed to be suggesting that it’s more likely to be an artifact of the trial design than a brexpiprazole effect suddenly emerging at Week 8. An interesting speculation was that perhaps brexpiprazole helped diminish rejection sensitivity right there at the end of the trial, when participants knew it was their last visit.
Notably, side effects were the reverse of what you might expect. Fifty percent of the placebo group reported a presumably medication-related problem, like nausea, fatigue, or restlessness, vs only 25% of the brexpiprazole group. The p-value for that difference is 0.03. Something’s going on there, although we’re not clear what it is though.
The authors suggest further study with a larger sample and a longer trial. But importantly, for more on this subject, if you have access to the American Journal of Psychiatry Archives, and if you haven’t seen that Gunderson review, it’s a very important position statement for our field. The review is linked here at the Psychopharmacology Institute.
Abstract
Background: Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals.
Aims: To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms.
Method: Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models.
Results: There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo.
Conclusions: Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.
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Reference
Grant, J. E., Valle, S., Chesivoir, E., Ehsan, D., & Chamberlain, S. R. (2022). A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder. The British Journal of Psychiatry, 220(2), 58-63.
Related References
Gunderson, J. G. (2016). The emergence of a generalist model to meet public health needs for patients with borderline personality disorder. American Journal of Psychiatry, 173(5), 452-458.
