DIVALPROEX SODIUM/PLACEBO IN BPD

Project: Research project

Project Details

Description

Borderline personality disorder (BPD) is a well-characterized
psychiatric disorder with an estimated prevalence of 1-2 percent of the
U.S. population, and high levels of impairment and mortality. BPD
accounts for approximately 10 percent of all psychiatric outpatients and
20 percent of acute inpatient hospitalizations. Core symptoms of BPD
include mood instability, anger, depression, psychoticism/paranoid
ideation, aggression and anxiety. In an open label study, we treated
11 BPD patients with the mood stabilizer divalproex sodium (DS). Of the
8 patients who completed treatment, 50 percent showed significant
improvement. There was a significant decrease in the SCL-90 total score
from 99.1 (q68.4) to 56.6 (q59.5)(t=2.8, p=.03). Global subjective
irritability showed significant decreases as well from 3.4(q0.55) to
1.7(q1.4)(t=3.0, p=.02). Improvement was also seen on clinical measures
of irritability, anger, anxiety and rejection sensitivity. In a pilot
double-blind placebo controlled trial of DS in 16 BPD patients, endpoint
CGI improvement scores were 2.0 (much improved) for DS and 5.0
(minimally worse) for placebo. There was significant improvement on
global functioning by GAS score (F=5.4, df=1,12, p=.04), aggression by
OAS-M (F=19.1, df=1,18, p=.005) and improvement on depression by BDI
from 15.5 to 6.9 on DS vs 14.7 to 12 on placebo. This and other
preliminary studies suggest potential efficacy of mood stabilizers such
as DS in BPD, which would complement existing nonpharmacologic treatment
modalities.
To further assess the efficacy of DS in BPD in the proposed small grant,
25 outpatients will be randomized to 10 week double-blind treatment with
DS vs placebo, preceded by a two-week placebo run in to establish
baseline levels on assessment measures. Clinical assessment of symptoms
and behaviors by a treating psychiatrist will occur on a weekly basis
for the first two weeks following initiation of treatment, then on an
every-other week basis for the following 8 weeks. An independent
evaluator, blind to dosage and side effects, will conduct assessments
every 2 weeks for global severity, psychoticism/paranoid ideation,
anger, anxiety and depression. Plasma valproate levels will be
monitored, and DS raised to a target value of 70-120 mug/ml. This small
grant (R03) will provide systematic information on the efficacy of DS
in the treatment of outpatients with BPD, as well as provide information
on feasibility, power, response rates, and reliability of outcome
measures which will form the basis of a larger RO1 proposal.
StatusFinished
Effective start/end date12/10/9911/30/01

Funding

  • National Institute of Mental Health: $84,367.00

ASJC

  • Psychiatry and Mental health

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