Abstracts

Rationale: Enzyme-inducing antiepileptic drugs (AEDs) have been shown to have effects on many areas of metabolism. A few studies suggest that these drugs might affect serum lipids and homocysteine (HCY), but serial measurements in adults with epilepsy have rarely been performed, and other serologic indices of vascular risk such as C-reactive protein (CRP) and lipid particle concentrations have never been examined in this context.Methods: We measured the serum lipid panel, lipid particle sizes and concentrations, lipoprotein(a) (Lp(a)), folate, vitamins B6 and B12, HCY, and CRP in 31 epilepsy patients on monotherapy with phenytoin (PHT) or carbamazepine (CBZ) who were not treated with a lipid-lowering agent. Each patient was then crossed over to monotherapy with levetiracetam (LEV) or lamotrigine (LTG), and the same variables were measured 6 weeks after discontinuation of the old drug. Lipid measurements, obtained in the fasting state, were performed by a specialty lipid laboratory. CRP was measured using a high-sensitivity assay. Analyses were two-tailed using either paired t-tests or Wilcoxon matched-pairs.Results: After switch to LTG or LEV, patients previously treated with CBZ or PHT showed average declines of 27 mg/dL in total cholesterol (213±40 to 186±32, p<0.0001). Most of this was in the atherogenic, non-high-density lipoprotein (non-HDL) cholesterol fraction (147±37 to 127±28 mg/dL, p=0.0004). HDL declined modestly (65±22 to 58±17 mg/dL, p=0.001). While overall serum low-density lipoprotein cholesterol (LDL) did not change significantly in either group, PHT-treated patients only (n=12) showed a mean decline of nearly one-third in the concentration of small LDL particles, a highly atherogenic subclass, after drug switch (831±650 to 559±450 nmol/L p=0.014). In addition, CBZ-treated patients only (n=19) showed average declines of 30% in Lp(a) (66±47 to 47±34 nmol/L, p<0.006) and almost 50% in CRP (5.3±6.7 to 2.8±5.5 mg/L, p<0.006) on the new AED. Despite elevations in B vitamins (significant only for B12, p<0.01), mean HCY levels remained essentially unchanged (10.8 ±3.6 to 11.3 ±4.2 μmol/L, p>