Potential conflict of interest: S.M., C.T.S., and M.R.S. engage in promotional speaking for UCB Pharma or Glaxo SmithKline, the manufacturers of levetiracetam and lamotrigine, respectively. The total amounts for each person are under $10,000 per year. These same physicians also participate in clinical trials for UCB Pharma through Thomas Jefferson University.
Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein†
Article first published online: 18 MAR 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 65, Issue 4, pages 448–456, April 2009
How to Cite
Mintzer, S., Skidmore, C. T., Abidin, C. J., Morales, M. C., Chervoneva, I., Capuzzi, D. M. and Sperling, M. R. (2009), Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol., 65: 448–456. doi: 10.1002/ana.21615
- Issue published online: 27 APR 2009
- Article first published online: 18 MAR 2009
- Manuscript Accepted: 10 NOV 2008
- Manuscript Revised: 8 NOV 2008
- Manuscript Received: 15 AUG 2008
- Epilepsy Foundation through the Edna Flaig Evans Trust
The widely prescribed anticonvulsants phenytoin and carbamazepine are potent inducers of cytochrome P450 enzymes, which are involved in cholesterol synthesis. We sought to determine whether these drugs have an effect on cholesterol and other serological markers of vascular risk.
We recruited 34 epilepsy patients taking carbamazepine or phenytoin in monotherapy whose physicians had elected to change treatment to one of the noninducing anticonvulsants lamotrigine or levetiracetam. Fasting blood samples were obtained both before and 6 weeks after the switch to measure serum lipid fractions, lipoprotein(a), C-reactive protein, and homocysteine. A comparator group of 16 healthy subjects underwent the same serial studies.
In the epilepsy patients, switch from either phenytoin or carbamazepine produced significant declines in total cholesterol (−24.8mg/dl), atherogenic (non–high-density lipoprotein) cholesterol (−19.9mg/dl), triglycerides (−47.1mg/dl) (all p < 0.0001), and C-reactive protein (−31.4%; p = 0.027). Patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) level (p = 0.0004), whereas those taken off phenytoin had a decrease in homocysteine level (−1.7μmol/L; p = 0.005). All of these changes were significant when compared with those seen in healthy subjects (p < 0.05). Results were similar whether patients were switched to lamotrigine or levetiracetam.
Switching epilepsy patients from the enzyme-inducers carbamazepine or phenytoin to the noninducing drugs levetiracetam or lamotrigine produces rapid and clinically significant amelioration in several serological markers of vascular risk. These findings suggest that phenytoin and carbamazepine may substantially increase the risk for cardiovascular and cerebrovascular disease. Ann Neurol 2009;65:448–456