Mäkinen Jussi, Rainesalo Sirpa, Raitanen Jani, Saarinen Jukka, Sandell Satu, Peltola Jukka
Department of Neurology Tampere University Hospital Tampere Finland.
Faculty of Social Sciences University of Tampere Tampere Finland.
Epilepsia Open. 2018 Jun 8;3(3):340-347. doi: 10.1002/epi4.12227. eCollection 2018 Sep.
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.
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.
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.
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.
已知强效酶诱导剂卡马西平(CBZ)治疗会影响血脂、类固醇和维生素D代谢。因此,有人推测服用CBZ的患者应改用非诱导性抗癫痫药物(AEDs)。然而,对于无癫痫发作的患者停用CBZ后的癫痫发作结局知之甚少。我们旨在通过一项对照观察性研究设计来解决这一问题。
对58例因担心长期不良反应而服用CBZ治疗局灶性癫痫的患者进行评估,以确定是否停用CBZ治疗;34例停止治疗,24例继续服用CBZ。六个月无癫痫发作是主要终点。此外,从所有患者中获取停药或继续用药前及停药或继续用药至少3个月后的血清样本(总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯、性激素结合球蛋白(SHBG)、游离睾酮和25-羟基维生素D水平)。
如果停用CBZ,无癫痫发作的患者癫痫复发几率升高5倍(95%置信区间[CI 0.51 - 49.3;p = 0.17])。与继续服用CBZ的患者相比,停药组患者的血清TC、LDL、HDL和SHBG水平显著降低,游离睾酮水平显著升高。甘油三酯和维生素D水平检测无显著变化。
无癫痫发作的患者停用CBZ似乎有中度但合理的复发风险。相反,我们的结果表明CBZ可能对血清TC、LDL、HDL、SHBG和游离睾酮水平有不利影响。