Conversion from enzyme-inducing antiepileptic drugs to topiramate: effects on lipids and C-reactive protein

We previously demonstrated that converting patients from the enzyme-inducers phenytoin or carbamazepine to the non-inducers levetiracetam or lamotrigine reduces serum lipids and C-reactive protein (CRP). We sought to determine if the same changes would occur when patients were switched to topiramate, which has shown some evidence of enzyme induction at high doses. We also examined the effects of drug switch on low-density lipoprotein (LDL) particle concentration.

We converted 13 patients from phenytoin or carbamazepine monotherapy to topiramate monotherapy (most at doses of 100-150 mg/day). Fasting lipids, including LDL particle concentration, and CRP were obtained before and ≥6 weeks after the switch. A group of normal subjects had the same serial serologic measurements to serve as controls.

Conversion from inducers to topiramate resulted in a -35 mg/dL decline in total cholesterol (p=0.033), with significant decreases in all cholesterol fractions, triglycerides, and LDL particle concentration (p≤0.03 for all), as well as a decrease of over 50% in serum CRP (p<0.001). Alterations in cholesterol fractions and CRP remained significant when compared to those seen in normal controls.

Changes seen when inducer-treated patients are converted to TPM closely mimic those seen when inducer-treated patients are converted to lamotrigine or levetiracetam. These findings provide evidence that CYP450 induction elevates CRP and serum lipids, including LDL particles, and that these effects are reversible upon deinduction. Low-dose TPM appears not to induce the enzymes involved in cholesterol synthesis.