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Several psychotherapeutic methods have randomized clinical trial evidence for benefit in borderline personality disorder. These include dialectical behavior therapy, mentalization, and a program called STEPPS (Systematic Training for Emotional Predictability and Problem Solving). With respect to pharmacotherapy for borderline personality disorder, a team which reviewed the literature in 2010 concluded that “the findings tend to suggest benefit from using second-generation antipsychotics, mood stabilizers, and omega-3 fatty acids and marginal effects for first-generation antipsychotics and antidepressants.” What’s new since 2010?
Hi! Jim Phelps here for the Psychopharmacology Institute. Let’s look at an update from Dr. Jutta Stoffers-Winterling and colleagues, beginning with antidepressants. First, 80[%] to 90% of people with a diagnosis of borderline personality disorder are taking an antidepressant. Since the 2010 review which found almost no support for the use of antidepressants, we have no new randomized trial data to change that picture.
An interesting randomized trial from the updated review comparing fluoxetine and dialectical behavior therapy (DBT) found that the suicide attempt rate was higher in the fluoxetine group. Reducing suicide attempts is one of DBT’s greatest strengths, so to pin the higher rate on fluoxetine itself would require comparing fluoxetine with DBT vs DBT alone. That was not the structure of this randomized trial, so what we see again is that DBT has the capacity to lower suicide attempts. As far as antidepressants, then, the authors of this 2020 update conclude, “given the high rates of antidepressant use in borderline personality disorder, the lack of relevant evidence is startling.”
Next, we’ll look at antipsychotics. What percentage of people with a diagnosis of borderline personality disorder are taking an antipsychotic? Again, the numbers are high, with rates ranging between 70[%] to 80% in inpatients and 35[%] to 60% for outpatients. Is this evidence supported? The authors’ previous Cochrane review emphasized that the evidence was slim, although not nonexistent. A 2014 randomized trial of quetiapine found that, after 8 weeks of treatment, scores on the Zanarini Scale—which is basically a measure of borderline symptoms and behaviors—were significantly lower on quetiapine than placebo. However, AstraZeneca, the manufacturer of quetiapine, contributed financially to that study and is listed as a collaborator on a recent extension. In addition, Dr. Stoffers-Winterling and colleagues note that there were 2 other trials of quetiapine listed at clinicaltrials.gov that were not published. So, perhaps these new 2014 results warrant at least our usual skepticism.
Nevertheless, here’s one interesting takeaway from this quetiapine study. The 300 mg was not clearly better than 150 mg daily and had more side effects. During the study duration of 10 weeks, the placebo and 150 mg groups gained an average of 1 pound, while the 300 mg group gained 3 pounds. This suggested that weight gain on quetiapine is potentially dose-related, which, if true, would strongly influence how we use it. A quick literature search on this question led me to a 2010 review of antipsychotic metabolic effects, and the evidence there was mixed regarding the dose–relatedness of adverse effects. I think that question may still be open.
For mood stabilizers, this update looks specifically at lamotrigine and valproate. In the authors’ 2010 review, they saw possible benefit from these medications, although it was tentative. A large randomized trial of lamotrigine published in 2018 in the American Journal of Psychiatry found that lamotrigine was no better than placebo, using that Zanarini scale that was used in the quetiapine study. This study was run through the period of 52 weeks, which is impressive, with a sample size of 137 in each group, which is also impressive. So, Dr. Stoffers-Winterling and colleagues conclude that lamotrigine is not a treatment option for borderline personality disorder.
What about lithium? Well, it’s not mentioned specifically in this update, so I took a quick look elsewhere. I discovered a 2010 review of medications for borderline personality disorder, in which lithium got 1 line, with 2 studies from 1972 and 1990. The latter was a comparison of desipramine with lithium, with an apparent sample size of 10. So, we might conclude that lithium is effectively unstudied in borderline personality disorder, which is remarkable given the accumulating data suggesting a protective effect against suicide. Of course, many clinicians will be hesitant to use a medication like lithium that is potentially fatal in overdose in this context.
One last update is that the authors’ 2010 Cochrane review concluded, “notably, avoidance of abandonment, chronic feelings of emptiness, identity disturbance, and dissociation were not found to be affected significantly by any drug.” However, the Zanarini Scale, which we’ve seen used in these more recent studies, includes items that specifically assessed these domains. In the 2014 quetiapine study, the 150 mg dose lowered participants’ Zanarini scores by 12 points—5 more than placebo. So, perhaps this 2010 conclusion about lack of impact on these symptoms warrants revision.
So, the authors’ 2020 conclusion is that “the prevalent use of medications in borderline personality disorder is still not reflected or supported by the current evidence.” For more on all this, the 2014 quetiapine study—lead author Donald Black—is worth critical examination.
Abstract
Pharmacotherapy for Borderline Personality Disorder: An Update of Published, Unpublished and Ongoing Studies
Jutta Stoffers-Winterling, Ole Jakob Storebø, Klaus Lieb
Purpose of the Review: We aim to identify the most recent evidence of randomized controlled trials evaluating continued drug treatments in people with a diagnosis of BPD, review the most recent findings, highlight trends in terms of currently ongoing studies and comment on the overall body of evidence.
Recent Findings: We identified seven new RCTs, plus newly available data for an older RCT. Only three of these RCTs have been published in full text, while we found study data posted at trial registry platforms for the others.
Summary: The new findings do not support fluoxetine as a treatment option for suicide and self-harm prevention. A large effectiveness study did not detect beneficial effects of lamotrigine in routine care. The prevalent use of medications in BPD is still not reflected or supported by the current evidence. More research is needed regarding the most commonly used substances and substance classes, i.e. SSRIs, and quetiapine, but also with respect to people presenting with distinct comorbid conditions.
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Reference
Stoffers-Winterling, J., Storebø, O. J., & Lieb, K. (2020). Pharmacotherapy for borderline personality disorder: An update of published, unpublished and ongoing studies. Current Psychiatry Reports, 22(8).
Related References
- Black, D. W., Zanarini, M. C., Romine, A., Shaw, M., Allen, J., & Schulz, S. C. (2014). Comparison of low and moderate dosages of extended-release Quetiapine in borderline personality disorder: A randomized, double-blind, placebo-controlled trial. American Journal of Psychiatry, 171(11), 1174-1182.
- Lieb, K., Völlm, B., Rücker, G., Timmer, A., & Stoffers, J. M. (2010). Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials. British Journal of Psychiatry, 196(1), 4-12.
