SAN FRANCISCO – Trials of drug therapy for borderline personality disorder have produced conflicting results and controversy, but a new trend is emerging: targeting medications to syndromes within the diagnosis.
Two or three recent meta-analyses of studies provide some support for this strategy, Dr. S. Charles Schulz said at the annual meeting of the American College of Psychiatrists, where he led an interest group discussion on drug therapy for borderline personality disorder.
Dr. S. Charles Schulz
"For the impulsive-aggressive borderline patients, the mood-stabilizing anticonvulsants have a very significant effect. For anger and cognitive or perceptual disturbance, the atypical antipsychotics are pretty good. For some depressed patients" with borderline personality disorder, the selective serotonin reuptake inhibitors (SSRIs) "can be useful," though they have a small effect in these patients, said Dr. Schulz, chair of psychiatry at the University of Minnesota, Minneapolis.
As a result, in the last 4 years or so, clinicians are thinking more in terms of targeting medications to subsets of patients rather than drug therapy for borderline personality disorder as a whole, he said. "That’s emerging" and is a strategy worth testing in prospective trials, Dr. Schulz said. The scant data in the meta-analyses are "nowhere near enough to fully support what these meta-analyses" suggest, he added.
No medications have been approved by the Food and Drug Administration to treat borderline personality disorder.
Research also is needed to build on preliminary studies of combining drug therapy with psychosocial therapy for borderline personality disorder, he said. One preliminary study found that people with borderline personality disorder who were randomized to dialectical behavior therapy (DBT) plus the atypical antipsychotic olanzapine showed significantly more improvement than did patients who got DBT plus placebo. "The strongest impact was on decreased danger," he said.
Studies of combining medications and psychosocial therapies are much more common for other psychiatric diagnoses than for borderline personality disorder, Dr. Schulz noted. "I would really like for us to step it up and mirror some of the other studies done for schizophrenia and bipolar disorder," he said.
He believes the National Institute of Mental Health should better fund large studies of drug therapy for borderline personality disorder, as it has for other diagnoses.
"I feel pretty passionately about this," Dr. Schulz said in an interview after the group discussion. "I’m pleased with the investment in the larger studies for bipolar disorder and schizophrenia. Borderline personality disorder is common, severe, and functionally impairing, and I believe we really need to understand it from a neurobiologic and psychologic vantage point."
Another problem is researchers’ preference in the past decade for enrolling "symptomatic volunteers" in studies of treatment for borderline personality disorder instead of enrolling diagnosed patients, he added. Soliciting symptomatic volunteers from newspaper advertisements or other methods can make a trial easier for researchers because they don’t have to withdraw patients from medications in order to participate, but it’s unclear whether results from such trials can be generalized to treatment of patients in clinics and hospitals.
"We have to look at some new methodology" to have confidence in results, he said.
Initial trials of drug therapy for borderline personality disorder in the 1980s suggested that some low-dose neuroleptic medications helped, the tricyclic antidepressant amitriptyline made approximately a quarter of patients worse, and the benzodiazepine alprazolam proved to be dangerously disinhibiting, he said. When SSRIs were introduced, a double-blind, placebo-controlled trial found that fluoxetine was helpful for impulsive and aggressive patients with borderline personality disorder.
Various studies of atypical antipsychotic medications since the 1990s produced conflicting results, claiming they do or do not help patients with borderline personality disorder when compared with placebo. Several placebo-controlled trials report that anticonvulsant mood-stabilizing drugs can be helpful, particularly for patients with borderline personality disorder and impulsive-aggressive behavior, he said.
With any medication, he advised physicians to titrate the dose slowly. "Start low, go slow, and be very careful of the exquisite sensitivity that some borderlines have to some medications, which in my opinion cannot be detected in a clinical interview," he said. At his institution, weekly case consultations bring psychiatrists and psychologists together to discuss the potential ramifications of drug therapy in a patient with borderline personality disorder.
Dr. Schulz has been an adviser to Biovail, Bristol-Myers Squibb, and Eli Lilly and has received grant support from AstraZeneca.