Clinical Trials for Treatment of Borderline Personality Disorder

To the Editor: There are currently no standard treatments for borderline personality disorder. Several psychotherapies have been developed, and a few are now considered evidence-based. Medications have also been explored, yet randomized controlled trials are few in number, leading to a lack of consensus regarding the best approach.

Despite the lack of Food and Drug Administration (FDA)–approved medications for the treatment of borderline personality disorder, most patients cared for in academic and community settings are prescribed medication in addition to psychotherapy—often more than one from different classes, leading to concerns regarding polypharmacy. Meta-analyses have concluded that there is evidence that some medications are effective, but more controlled clinical trials are needed to confirm and extend these observational findings.

To address the potential benefit of quetiapine (approved by the FDA for schizophrenia and bipolar disorder), we conducted a double-blind, placebo-controlled study, which was investigator initiated and sponsored by AstraZeneca. The results showed positive effects of the lower dose tested (150 mg/day), with more than half responding as defined by a 50% decrease in symptom ratings (1). There were fewer such effects at the higher dose, and there were more side effects and patient attrition. The report was accompanied by an editorial appropriately noting the strengths and limitations of the study, including its 8-week duration for an illness that often lasts many years (2).

Two subjects initially enrolled at the University of Minnesota site were immediately dropped from the study when their misuse of the study medication was discovered. The University Internal Review Board reviewed what occurred and concluded that we had acted appropriately. Nonetheless, a member of the Ethics Center alleged to the New York Times that the investigators had acted irresponsibly. The newspaper reported this allegation in a recent issue and did not include a statement to the newspaper from the University of Minnesota that no investigator misconduct had occurred.

Many large clinical trials have had issues with behavioral problems and protocol violations by some subjects, and for these reasons all such studies have procedures to dismiss subjects. Such problems are part of both clinical and research care with seriously ill patients. Despite this subject misconduct, the results of the study provide clinicians and patients with new evidence-based guidance on dose, effectiveness, and side effects of quetiapine in borderline personality disorder. The next step is to examine the effect of quetiapine in borderline personality disorder patients in combination with an evidence-based psychotherapy. Our patients deserve no less than the continued investigation of our options for their treatment.