Abstract
The antiepileptic topiramate is also used to treat pain [1], bulimia [2], acute mania [3], and aggression [4]. Only a few controlled trials have tested topiramate in the treatment of pathological aggression associated with borderline personality disorder (BPD) [5–7].
One such double-blind, placebo-controlled study was conducted in 2004. Men with BPD were treated with up to 250 mg topiramate daily (TG: n = 22) or with placebo (PG: n = 22) for 8 weeks [6]. Significant changes on the State–Trait Anger Expression Inventory (STAXI) were documented.
We conducted an 18 month open-label follow up to that study, ending in January 2006, in order to assess the long-term influence of topiramate on the subjects’ aggression. The subjects (TG: n = 22; former placebo group (Ex-PG): n = 22) were examined biannually with STAXI. Intermediate results were not analysed during the trial. We tested and physically examined both groups for the last time after 18 months. Twelve patients dropped out.
A two-factor repeated measures analysis of variance was performed. The treatment condition was defined as the between-subject factor and the measurements in time as the within-subject factor. When the assumptions for the repeated measures analysis were not given, the results were adjusted with the Greenhouse–Geisser epsilon. To assess the differences at the initial and final points, multiple comparisons were performed with contrasts for each treatment condition. The significance levels were corrected with the Bonferroni correction.
After 18 months, according to the intent-to-treat principle, the repeated measures analysis showed a significant interaction for the group×time effect for all STAXI scales (State–Anger, Trait–Anger, Anger In, Anger Out and Anger Control, all p < 0.01). The group effect was likewise significant for all scales (all p < 0.01).
The TG also experienced a more significant reduction of the bodyweight than the former placebo group (TG: initial weight mean value (MV) = 87.5±3.8 kg, follow-up final weight MV = 76.9±3.8 kg; Ex-PG: initial weight MV = 86.8±5.8 kg, follow-up final weight MV = 83.8±3.3 kg; p(IE) = 0.65, p(FE) = 0.01, p(group×time effect) <0.01, p(group effect) <0.01). Fatigue, dizziness, headache and paresthesia were occasionally reported. No psychotic symptoms or severe cognitive impairment were observed. Four subjects engaged in self-mutilation (one in TG) or suicidal acts (none in TG) during the study.
Throughout the observation period, the TG experienced a significantly greater change than the PG/Ex-PG on all STAXI scales. Topiramate showed greater efficacy in treating subjects’ aggression, which confirms the original trial [1]. The intra-psychological processing of aggression, as well as control of anger, may have been influenced, because TG subjects sensed a reduction in both the intensity of anger and the threshold for perceiving it. Topiramate was relatively well tolerated.
Following lengthy treatment, topiramate appears to be a safe agent with sustained efficacy for reducing aggression in men with BPD.