Abstracts

RATIONALE: Epidemiological and clinical studies have demonstrated that serum lipids are closely related to the development of coronary artery disease and every 1% increase in total cholesterol results in 2% increase in the risk of developing coronary artery disease (CAD). A number of studies have reported the evidence that long-term antiepileptic drug therapy influences total cholesterol. The effect of Divalproex Sodium (DVPX) dosing on total cholesterol has not been systematically studied in epilepsy.
At the end of this activity the participants should be able to discuss the effect of two DVPX dosing regimens on total cholesterol in patients with complex partial seizures.
METHODS: A retrospective analysis of a randomized, double-blind, parallel-group, monotherapy trial comparing two dosing regimens of DVPX in adult patients with complex partial seizures was conducted. Subjects were randomized to two groups: high dose DVPX with target serum concentration of 80-150 mcg/ml, and low dose DVPX with target serum concentration of 25-50 mcg/ml. A variety of metabolic parameters were analyzed. Concomitant AEDs were withdrawn after target concentrations were attained.
RESULTS: Data from all 265 subjects who received randomized study drug were included in this analysis. 134 of those subjects were treated with high dose DVPX and 131 subjects were treated with low dose DVPX. The average daily dose of DVPX in the high dose group was 3370 (+/-1053.0) mg/day. The average daily dose of DVPX in the low dose group was 1294 (+/- 434.4) mg/day. The entry characteristics of the two groups, the history of antiepileptic medications use and the use of concomitant medication with metabolic properties taken during the study were similar. Mean serum cholesterol levels decreased by 34.4 mg/dL in the high dose group and by 19.7 mg/dL in the low dose group (p[lt]0.001). Mean change in glucose levels was not significantly different between the two groups (p=0.122). Changes from baseline to final evaluation in total protein, albumin, and SGOT were significantly different between the two treatment groups. Total protein was decreased by 0.49 mg/dL in high dose DVPX group and by 0.21 mg/dL in low dose DVPX group (p[lt]0.001). Albumin was decreased by 0.61 mg/dL in high dose DVPX group and by 0.27 mg/dL in low dose DVPX group (p[lt]0.001). SGOT was increased by 19.9 mg/dL in high dose DVPX group and by 6.5 mg/dL in low dose DVPX group (p[lt]0.001). None of these changes were clinically significant. Mean weight increased by 1.3 (+/- 6.4) Kg in the high dose DVPX group and by 2.0 (+/-5.0) Kg in the low dose DVPX group (p=0.380).
CONCLUSIONS: DVPX significantly decreased total cholesterol and this decrease was dose related. This reduction in cholesterol was observed despite an increase in weight. Cholesterol lowering effects of DVPX has also been reported from preliminary data in patients with bipolar disorder.
[Supported by: This study was funded by Abbott Laboratories.]; (Disclosure: Salary - Abbott Laboratories, Grant - Abbott Laboratories, Stock - Abbott Laboratories)