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Seroquel XR Helps in Borderline Personality Disorder

Last Updated May 7, 2014
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NEW YORK CITY -- Patients with borderline personality disorder showed significant improvements when treated with long-acting antipsychotic agent quetiapine fumarate (Seroquel XR) in a placebo-controlled trial, a researcher said here.

Scores on the Zanarini Rating Scale for borderline personality disorder declined significantly more in the 8-week trial among those taking 150 mg/day of extended release quetiapine than did those in the placebo group, reported , of the University of Iowa in Iowa City.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • A randomized, double-blind, placebo-controlled, study of the use of quetiapine fumarate in the treatment of adults with borderline personality disorder found a significant reduction in the severity of symptoms of compared with those receiving placebo.

Although a dose of 300 mg/day failed to show a significant advantage over placebo in Zanarini score -- the study's primary endpoint -- both doses improved patients' symptoms on a host of other measures, Black told attendees at the .

Pharmacotherapy, usually with antipsychotic drugs, is commonly used to treat borderline personality, but rigorous double-blind trials have been few and far between. No drug currently carries an approved indication for the condition, so all prescribing is off-label.

, of the University of Pittsburgh, who was not involved with the study, told app that drug companies have generally shied away from sponsoring studies or seeking FDA approval for a borderline personality indication for their products.

Borderline personality disorder -- a condition marked by extreme emotional lability and impulsivity -- has a high rate of suicide, said Soloff, who is a prominent figure in borderline personality research. As a result, drug firms may have been worried that suicides in a clinical trial would have negative repercussions for their products.

The current study was funded by quetiapine's maker, AstraZeneca.

Study Details

Black and colleagues randomized 95 patients who were recruited by advertisements and referrals to the two doses of quetiapine or placebo. All patients were started at a dose of 50 mg on the first day and then raised to 150 mg on day two; those assigned to the 300-mg dose were raised to that level after 4 weeks.

Patients had to be ages 18-45, meet DSM-IV criteria for borderline personality, and show a Zanarini score of at least 9 at screening.

Those who had a variety of other psychiatric and nonpsychiatric conditions -- ranging from pregnancy to recent suicidality -- were excluded. So were patients who had previously failed to respond to an atypical antipsychotic drug.

In addition to the primary endpoint of relative change in Zanarini score, secondary outcomes included the so-called BEST index of borderline personality symptoms as well as seven measures of depression, aggression, mania, impulsivity, and global functioning.

At the final evaluation, patients in the three study arms showed the following declines in Zanarini score (reflecting symptom improvement):

  • Placebo: -6.3 points
  • 150 mg quetiapine: -10.6 points (P=0.03 versus placebo)
  • 300 mg quetiapine: -9.7 points (P=0.27 versus placebo)

The same pattern was seen in a responder analysis. Proportions of the three groups showing declines of at least 50% in Zanarini scores from baseline were 82% with 150 mg of quetiapine, 67% with 300 mg, and 62% with placebo. Again, only the 150-mg group showed a significant difference from placebo.

Black noted that a complicating factor in the statistical analysis was that patients randomized to quetiapine, and especially the 300-mg group, had significantly more severe symptoms at enrollment almost across the board relative to those assigned to placebo. Statistical results were adjusted for baseline severity.

On all the secondary measures, the 300-mg group showed significantly greater improvement than did the placebo group. This was also true for the 150-mg group, except that the difference from placebo in Young Mania Rating Scale scores just missed significance (P=0.06).

About one-third of participants discontinued prematurely. There was not a statistically significant difference in rates among the three study arms, but a dose-dependent trend was apparent. At week eight, about 42% of those in the 300-mg group had quit, compared with 33% of the 150-mg group and 20% of those assigned to placebo.

Symptom severity did not appear to predict discontinuation, but reports of sedation did. Black and colleagues found that sedation was associated with discontinuation with a hazard ratio of 1.77 (95% CI not reported) compared with participants not reporting sedation.

This factor was especially apparent with the higher quetiapine dose. Patients in this group were twice as likely to show sedation relative to the placebo group.

Other adverse effects that were more common with high-dose quetiapine were change in appetite and dry mouth. Weight gain did not appear to be an issue, although the trial was only 2 months long.

Black said that the high-dose group might have shown better efficacy and adverse event results if dose reductions had been permitted in the study protocol, but these were not allowed. In practice, he suggested, dose reductions would be normal in patients with side effects that make them want to stop the drug.

He recommended another trial with larger patient numbers and with active comparators to provide better understanding of the effectiveness and safety of atypical antipsychotics for borderline personality.

Role of Drug Treatment

Soloff told app that the choice of drug treatment in this condition is heavily dependent on individual patient presentations. Psychotherapy is always the mainstay of treatment, he said, with pharmacotherapy added on either right away or if psychotherapy alone is not controlling symptoms.

He said patients have to participate actively in psychotherapy for it to work, and some are too unstable for this to be possible.

"If your patient is having so much difficulty with impulsivity, with affective instability -- their moods go up, down, up, down -- with anger management issues, in order to engage them in psychotherapy, you have to put out the fire first," he said. "You have to have a patient who will come to your office and sit and tolerate what you're doing."

He added that drug effects are generally modest, "reducing the severity of symptoms" rather than completely normalizing them, and with different drug types mainly targeting parts of the symptom spectrum. Antipsychotics, for example, are most effective in diminishing anger and, to a lesser extent, impulsivity and paranoid ideation, whereas mood stabilizers reduce affective swings.

Soloff had no opinion on whether quetiapine would or could be preferred over other atypicals. However, he said that a formal FDA approval for a borderline personality indication would probably tilt the balance in its favor for many clinicians.

Black also suggested that there was no particular reason to think that quetiapine would outperform other agents in its class. He said it was the focus of the current study because the manufacturer instigated it.

AstraZeneca hasn't indicated whether it plans to conduct more trials or to pursue an FDA approval for the indication.

Other drugs now being tested in placebo-controlled trials for borderline personality disorder include the antidepressant , the dopamine agonist , and the stimulant , among currently approved drugs. None of these appear to be sponsored by their manufacturers.

In the antipsychotic class, a small placebo-controlled trial of low-dose risperidone (Risperdal) to be conducted in Israel was announced in 2004, with completion slated for 2009. Its outcome remains unclear as no results were posted on Clinicaltrials.gov.

The site list several other small studies as underway with agents such as and an .

Disclosures

The study was funded by AstraZeneca.

Study authors reported relationships with AstraZeneca, Otsuka, Myriad RBM, Eli Lilly, Genentech, and several publishing firms.

Soloff declared he had no relevant financial interests.

Primary Source

American Psychiatric Association

Source Reference: Black D, et al "A randomized controlled trial of extended-release quetiapine in the treatment of borderline personality disorder" APA 2014; Abstract SCR08-2.