Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction

Abstract

Objective: Treatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure-free patients. We aimed to address this issue using a controlled observational study design. Methods: Fifty-eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long-term adverse-effects; 34 discontinued its therapy and 24 continued with CBZ. Six-month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, sex hormone–binding globulin (SHBG), free testosterone, and 25-hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients. Results: Seizure-free patients had a 5-fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51–49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected. Significance: Discontinuation of CBZ in seizure-free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.