1 Boring Old Man

Clinical Trials for Treatment of Borderline Personality Disorder

by S. Charles Schulz M.D. and Donald W. Black, M.D.

American Journal of Psychiatry. 2015 172[8]:793.

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…

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. 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.

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.

Seroquel in the oatmeal at the sex offender facility: Schulz replies

Fear and Loathing in Bioethics

by Carl Elliot

August 1, 2015

If you recall, in April the Times reported yet another mismanaged clinical trial in the U’s Department of Psychiatry. Two sex offenders were recruited into a clinical trial of Seroquel for Borderline Personality Disorder, despite the fact that they did not actually have the disorder. Then one of them slipped his study medication into the oatmeal at the facility where he was housed. According a report from Alpha House, the sex offender facility:

Some residents noticed pink particles in the oatmeal. After eating breakfast the residents and staff reported feeling sedated and some were "knocked out’ for the remainder of the day. Staff asked X if he had put the study medication into the oatmeal and he denied it. After failing a polygraph test X was re-imprisoned…

Under guidelines governing federally funded clinical trials, the men would have been considered prisoners and their participation given special scrutiny, several outside ethics experts said. Although the trial was not federally funded, many universities follow similar rules for research involving human subjects. [The university asserts the men were not prisoners.]

Other concerns about the study were raised even before the oatmeal drugging. The study’s safety officer, Dr. Scott Crow, noted in a memo that not a single patient had failed the screening process for enrollment in the study, even though outside experts said it was unlikely that everyone who applied would meet the criteria. Dr. Schulz said the failures were not recorded because the patients were formally screened only after undergoing initial telephone interviews that eliminated unlikely candidates.

“What a sloppy trial,” said Nancy Dubler, a bioethicist who served for years on the Institutional Review Board, or I.R.B., at Montefiore Medical Center in the Bronx. She is an expert on the inclusion of prisoners in clinical trials and said closer attention should have been paid to the events at Alpha…

Borderline patients come in many sizes and shapes. They are united as a group by certain shared phenomena with varying intensity. They are intolerant of being alone. They tend to simplify other people [good/bad] and any given person can jump from one to the other designation in a heartbeat. They are needy, but confused about what they need, so they end up coercing others into doing things that are ultimately to their own detriment. Rather than having periodic life crises, they often live crisis lives in a pattern where the solution to the last problem/crisis sets the stage for the next problem/crisis. The term "borderline" stuck because they confound every treatment. The basic difficulty is an infantile need for attachment combined with an equally infantile inability to maintain a consistent view of another. As I said in an anachronism… and Academic·Industrial·Complex II…, the notion that any drug will have a lasting benefit is unlikely. They go through drugs just as they go through people [and therapists]. So the clinical trials are more for the sponsors than the afflicted. They are treatable with modified therapies – psychodynamic or behavioral [dialectic behavior therapy] – but in either case, it is "heroic" psychotherapy and success is hardly guaranteed. Antics like the ones reported here [the Seroquel in the oatmeal] or sexual acting out [polymorphous sexual perversion] are not uncommon. While I’ve focused here on the difficulty these patients pose for others, they live difficult and painful lives and successful treatment is well worth the effort if it can be mustered.

So back to my response of sadness to the letter. I don’t get the sense that Dr. Schulz really understands the Borderline patients and where they hurt. He sure didn’t understand Katie Thomas’ article in the NYT [A Drug Trial’s Frayed Promise], what Carl Elliot was getting at, and why some statement from UMn was immaterial. I had the same feeling when I read that oral history interview [Interview with S. Charles Schulz, M.D.]. He was troubled by Carl Elliot’s campaign about Dan Markingson, but seemed clueless about why Carl was so upset and persistent. The place where I felt it most strongly was in his response to a letter from Mary Weiss back in the day, worrying about her son – Dan Markingson’s psychotic state. Instead of going to see Dan to see what she was talking about, he conclaved with co-investigator Dr. Stephen Olson to frame a response letter saying that they were doing nothing wrong.

Patients with First Episode Schizophrenia or Borderline Personality Disorder are in intense emotional tangles. They aren’t orderly. They don’t fit into routines. They’re too busy inside their minds and need a lot of attending to. Even the "sex offender" who flavored the oatmeal with his Seroquel was probably actually "Borderline" and needed to be seen rather than just removed for bad subject behavior. Dan Markingson was definitely in need of being seen at the time his mother wrote her frantic plea, not dealt with by a falsely reassuring letter. Carl Elliot and Leigh Turner of the University’s Bioethics Department deserved to be seen and engaged rather than discounted from afar – treated as nuisances. Reading of Dr. Schulz’s plans to make the UMn a Research Center for Psychiatry when he came to Minnesota and his pride in building his program in the Interview with S. Charles Schulz, M.D. added to the sad feeling, because he didn’t seem to grasp that his remoteness, lack of active engagement, and defensiveness was much of the reason things finally went so badly for him, for Dan, for his program.