Women with borderline personality disorder who took the anticonvulsant
topiramate displayed less anger compared with those on placebo, said German
researchers. They also lost weight, an important consideration for a class of
drugs that often provokes weight gain.
The research extends evidence of the use of anticonvulsant medications like
valproate and carbamazepine in the treatment of pathologic aggression, said
lead author Marius K. Nickel, M.D., of the Clinic for Psychosomatic Medicine
in Simbach/Inn, Germany. Earlier trials had tested topiramate's effects on
aggression, but this is the first such placebo-controlled study, he said.
"Anger and aggression are big problems in borderline personality
disorder, so even a small trial like this is welcome," said Frances
Frankenburg, M.D., a psychiatrist at the Veterans Affairs Medical Center in
Bedford, Mass., and an associate professor of psychiatry at the Boston
University School of Medicine. "It's always nice to have studies from
Europe to gain a different perspective."
Through general practitioners, the German researchers recruited volunteers
who expressed feelings of constantly increasing anger in screening interviews.
They were randomized in a 2:1 ratio to topiramate (n=19) or matching placebo
(n=10). Eight weeks of topiramate treatment began at 50 mg a day and was
titrated up to 250 mg a day at the end of six weeks. Subjects were seen weekly
in the clinic and tested using the German-language version of the State-Trait
Anger Expression Inventory (STAXI), a 57-item inventory that measures the
intensity of anger as an emotional state and the disposition to experience
angry feelings as a personality trait, according to its distributor.
Topiramate resulted in statistically significant improvements on four out
of five subscales of the STAXI, reported Nickel in the November 2004
Journal of Clinical Psychiatry. The women taking topiramate improved
their scores on the STAXI stateanger subscale score (measuring their
subjective state of anger) by 21 percent. Trait-anger, the readiness to react
with anger, improved by 24 percent, while the tendency to direct anger
outward, anger-out, improved by 23 percent compared with placebo.
Anger-control, the socially desirable ability to keep anger under control,
strengthened by 13 percent.
There was a positive, but not significant, 8.5 percent change favoring
topiramate on the scores for anger-in, the tendency to repress anger.
Since the women were tested with the STAXI protocol every week, it was
possible to see that the beneficial effect of the drug began modestly but
produced a rapid improvement after approximately the fifth week, said
"No psychotic symptoms or other serious side effects were observed,
nor did subjects in either treatment group engage in self-mutilation or
suicidal acts during the study," he said. Isolated cases of fatigue,
dizziness, headache, and paresthesia were reported as side effects.
However, the relative brevity of the trial may have also contributed to its
apparent safety, cautioned Frankenburg.
"Topiramate may be hard to tolerate over the long haul because it
induces cognitive decline," she said. She also expressed concern about
the drug's safety in pregnancy, since anticonvulsants may cause birth defects.
Women in this trial averaged 25 years old but were excluded if pregnant or
contemplating having a baby.
Other anticonvulsant mood stabilizers, like valproate or carbamazepine, can
cause patients to gain weight. The patients in this trial lost an average of
2.3 kg during the course of the study, somewhat less than in previous tests of
topiramate, said Nickel. "Reduced appetites and weight loss were
observed and usually seen as beneficial."
Losing weight may seem like good news for patients and an incentive for
compliance, but other drugs that cause weight loss early in clinical trials
have evidenced problems later, said Frankenburg. "I'm a bit of a
puritan," she said. "The secret of weight loss is to eat
The researchers say their work now needs to be replicated among larger
numbers of patients, among men, among more severely ill patients, and for
longer periods of time. The brief, eight-week duration of this trial reduced
the dropout rate, a problem that often undermines the validity of longer
trials, they said.FIG1
The authors reported no financial affiliation or other relevant conflicts
An abstract of "Topiramate Treatment of Aggression in Female
Borderline Personality Disorder Patients: A Double-Blind, Placebo-Controlled
Study" is posted online at<www.psychiatrist.com/abstracts/200411/110410.htm>.▪