Borderline Personality Disorder Medication Information - From the National Institute of Mental Health (NIMH)

Jim Breiling, Ph.D.
National Institute of Mental Health
6101 Executive Blvd., Room 6-179
Bethesda, MD 20892-9651
(Express or Courier Service: Rockville, MD 20852)
E-mail: jbreilin@mail.nih.gov 
Voice: 301-443-3527
Fax: 301-443-4611

Borderline Personality Disorder Medication

June 1, 2004

Kudos to Dr. Antonia New and her collaborators in Larry Siever's program on a very nice step (see citation and abstract below) toward opening the black box between treatment and outcome with knowledge about the likely mechanism of change in the brain; in this case, the illumination of the mechanism of change is for a pharmacological treatment that reduces impulsive aggression in patients with borderline personality disorder.

As with any research, questions come to mind:
Since placebo seems to have many of the same effects as fluoxetine, does this medication have effects on the brain and on impulsive aggression beyond what would be obtained with a placebo?

When, if ever, do the pharmacologically effected changes in the brain and in impulsive aggression become enduring so that continued use of medication is no longer necessary? If enduring effects are obtained from a limited duration of pharmacological treatment, do the brain changes associated with enduring effects differ from those initially associated with changes?

Can psychotherapy produce similar brain and behavior changes, and if so, what therapy methods do so most quickly and powerfully, and are such changes enduring? Does psychotherapy obtain reductions in impulsive aggression, but through different mechanisms (different changes in the brain)? If so, what are the implications?
.
What is the optimal relation between pharmacological and psychosocial treatment for impulsive aggression in borderline personality disorder?
-- Jim Breiling

Psychopharmacology (Berl). 2004 May 25
Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression.

New AS, Buchsbaum MS, Hazlett EA, Goodman M, Koenigsberg HW, Lo J, Iskander
L, Newmark R, Brand J, O'Flynn K, Siever LJ.

Psychiatry Service-Mount Sinai School of Medicine and the Bronx VA Medical
Center, 130 West Kingsbridge Road, PO Box 1168, 10468, Bronx, NY, USA.

RATIONALE. Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. OBJECTIVES. The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET. METHODS. Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks.
Anatomical MRIs were coregistered to PET and relative metabolic rates were
obtained in 39 Brodmann areas. RESULTS. Brodmann areas 11 and 12 in the
orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified. CONCLUSIONS. These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.

May 19, 2004

There have been great responses to the issue of how to handle medications in Borderline Personality Disorder research. Unfortunately, in cutting and pasting to put them together in a single, organized posting, I did something that seems to have sent the compilation in to electronic never never land, and I have not been able to locate much less recover the item from that world of the lost. With that frustrating experience as a spur, I am posting below input that I received this morning on the medication issue from Don Black. (The STEPPS trial that he mentions is a NIMH treatment evaluation for BPD; I have pasted the CRISP abstract for it at the end of this note.) Your reactions? -- Jim Breiling

Hi Jim - I apologize for the late response to this email, but think the issue of how medication is handled is very important. In our STEPPS trial, we decided that BECAUSE medication use is so widespread, it was something we could not control well. Further, any psychosocial trial that ignores medication usage simply will NOT reflect the real world, and in my view the findings will be suspect. We opted to record during the trial what medications were used, dosages, etc., and to (at the time of data analyis) control statistically for them. I believe that because patients are randomly
assigned to STEPPS or treatment as usual (TAU) that the medication comparison will be a non-issue, and that the amount of meds used - at least initially - will be the same. By tracking medication use, one of our outcome variables will be overall usage at the end of the trial. Bateman and Fonagy looked at medication use and found that as their trial progressed, those receiving the psychosocial treatment actually used LESS medication. Because borderline patients are so unstable and have so many target symptoms, that to freeze the medication at the time of study entry and not permit changes, will not be workable, and that treating doctors will make changes anyway.
Control of medication makes no sense to me unless the study is a medication
trial. Does this help??? DWB

April 27, 2004

Last month the NIMH special review group meet for the 25 applications that were submitted under the reissued RFA for exploratory/developmental translational research for borderline personality. Two issues arose so frequently then in the discussion of scored application that a review group member recommended that NIMH program (i.e., me) work with the community of borderline personality disorder researchers to, if possible, arrive at agreement on guidelines for handling these issues. Such an agreement might well enable significant improvements in the priority score ratings of
applications and thereby increase the likelihood of funding.

The two issues are (1) how medications will be handled and (2) the appropriate control or comparison group(s).

To anticipate a likely question: Was there an approach or several approaches that reviewers felt were better. I have been going through the written critiques, and find that we're on our own for coming up with better (or at least acceptable) ways.

I'm not sure what the best way to proceed is for facilitating the discussion of these two issues. Your suggestions, now or later, will be welcome,

To start this journey I thought I would present the essence of the various plans for handling medication and for the comparison or control groups.

Below is the essence of one plan for handling medications:

Maintain current medications, ascertain what they are, and examine statistically for possible effects.

Is this acceptable? Is it statistically viable? If not acceptable, why not? What would be better?

I look forward to your comments.


Jim Breiling, Ph.D.
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Grant Number: 5R01MH063746-02
PI Name: BLACK, DONALD W.
PI Email: donald-black@uiowa.edu
PI Title: PROFESSOR
Project Title: A Cognitive Group Treatment for Borderline Outpatients

Abstract: The goal of this project is to test the efficacy of a new cognitive-behavioral systems-based group treatment for persons with borderline personality disorder (BPD) and to compare it to "treatment as usual" (TAU). We elected to modify a program originally developed by Bartels and Crotty. This led us to develop STEPPS, an acronym that stands for Systems Training for Emotional Predictability and Problem Solving. Briefly, the program involves both cognitive-behavioral techniques and skills training combined with a systems component; the latter involves the patients with BPD and those in their system, including family members, friends, and health care professionals. STEPPS involves twenty 2-hour group meetings with two facilitators; the therapy is manual-based and each week specific goals are set. We propose to recruit approximately 160 adults with DSM-IV BPD during the first 2 1/2 years of the project. Subjects will be recruited through referral from area psychologists, psychiatrists, mental health clinics, and hospitals. Subjects will be screened using the Revised
Diagnostic Interview for Borderlines (DIB-R) and relevant sections of the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). Appropriate subjects meeting specified inclusion/exclusion criteria will be randomized to STEPPS or TAU. Subjects in both groups will be allowed to continue to see their psychiatrist, take psychotropic medication, and continue with other therapy. Baseline assessments will include the Structured Clinical Interview for DSM-IV, the SIDP- IV, the Hollingshead Scale, the Social Adjustment Scale, the Beck Depression Inventory, the Positive and Negative Affectivity Scale, the Symptom Checklist-90-R, the Barrett Impulsivity Scale, and the
Medical Outcomes Study Short Form Health Survey. A new self-rated scale, the
Borderline Evaluation of Severity Over Time (BEST), will also be used to rate BPD symptoms. Subjects will be assessed at baseline, and at weeks 4, 8, 12, 16, and 20. Lay and professional support system members (informants) will be asked to rate the subjects progress at specified intervals. Satisfaction with STEPPS and TAU will be assessed in informants and subjects at the conclusion of the trial. Therapy fidelity will be maintained through regular supervision, and blind ratings of videotaped sessions. Subjects randomized to STEPPS will be followed up at months 1, 3, 6, 9, and 12
post-study completion. We hypothesize that subjects participating in STEPPS will have better symptomatic improvement than subjects receiving TAU; improvement will include greater mood stability, less deliberate self-harm, less anger/impulsivity, and lower rates of health care utilization. We hypothesize that the gains of STEPPS will be maintained over 1 year. These findings should add to our understanding of the appropriate clinical management of BPD. If the efficacy of STEPPS is confirmed, future studies will include larger samples to help test whether specific subgroups will
preferentially respond, and comparisons of STEPPS to other programs,
including Dialectical Behavior Therapy.

May 19, 2004

Seth Mandel agrees with Don Black on medications in treatment studies, but note that the prescribing psychiatrists should be equivalent across groups, that he is holding medication constant for a medication trial, with adverse impact on recruiting, and that a decrease in number of medications could be an outcome measure of success for psychotherapy. -- Jim Breiling

I agree that this is the best way to handle the issue of medication while making the results gerneralizable. I have found great variability in appropriate use of medication in borderline patients, but as long as both groups are seeing the same type of psychiatrist, i.e. one group isn't seeing psychiatrists who specialize in the pharmacologic management of BPD, then the medication issue can be handled appropriately. I am doing a medication trial and I have found the need to freeze other medications during the trial to be somewhat of a barrier to recruitment. It has also been my finding that pts require less medication over time with good psychotherapeutic
interventions (DBT at my hospital) and I often try and streamline regimens as pts become more stable. Decrease in medication, at least the number of drugs a pt is on at the end of the study could be a valuable outcome measure of a successful psychotherapeutic intervention.

Seth Mandel
The Zucker Hillside Hospital

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