抗癫痫药物对卒中后癫痫患者血清同型半胱氨酸、叶酸、B族维生素水平的影响

目的探讨4种常用抗癫痫药物(AEDs)对卒中后癫痫(PSE)患者血清同型半胱氨酸(Hcy)、叶酸、维生素B_(12)、维生素B_6水平的影响。方法对规则口服AEDs 1年以上的194例PSE患者(AEDs治疗组)及新诊断未服药的40例PSE患者(对照组)进行血清Hcy、叶酸、维生素B_(12)、维生素B_6水平检测。探讨不同AEDs对患者上述指标的影响。结果与对照组相比,AEDs治疗组血清Hcy水平明显增高,血清叶酸、维生素B_(12)水平明显降低(均P0.05)。各组间血清维生素B_6水平的差异无统计学意义。与单药治疗亚组比较,联合用药亚组血清Hcy水平明显升高(P0.05)。与对照组相比,采用丙戊酸钠(VPA)、卡马西平(CBZ)、奥卡西平(OXC)单药治疗的患者血清Hcy水平显著增加,采用VPA、CBZ单药治疗的患者血清叶酸水平明显降低,采用VPA单药治疗的患者血清维生素B_(12)水平明显降低(均P0.05)。与对照组相比,采用VPA+CBZ、VPA+左乙拉西坦(LEV)、VPA+OXC、CBZ+LEV双药联合治疗及≥3种AEDs联合治疗的患者血清Hcy水平显著增加,采用VPA+LEV、VPA+OXC、CBZ+LEV双药联合治疗及≥3种AEDs联合治疗的患者血清叶酸水平明显降低,采用VPA+CBZ、VPA+OXC、CBZ+LEV双药联合治疗及≥3种AEDs联合治疗的患者血清维生素B_(12)水平明显降低(均P0.05)。AEDs治疗组高Hcy血症(HHcy)发生率(36.6%)明显高于对照组(20.0%)(χ~2=4.085,P=0.043)。其中联合用药亚组HHcy发生率(47.6%)与对照组比较差异有统计学意义(χ~2=6.950,P=0.008);单药治疗亚组HHcy发生率(33.6%)与对照组比较差异无统计学意义。VPA、CBZ单药治疗的患者HHcy发生率(40.5%;43.8%)明显高于对照组(χ~2=3.871,P=0.049;χ~2=4.726,P=0.030)。OXC、LEV单药治疗的患者HHcy发生率(29.2%;22.9%)与对照组比较差异无统计学意义。结论AEDs治疗对PSE患者血清维生素B_6水平的影响不大,但对其血清Hcy、叶酸、维生素B_(12)水平影响较大。联合应用AEDs或VPA、CBZ单药治疗可能增加PSE患者HHcy的发生率。     

左乙拉西坦和传统抗癫痫药体外诱导大鼠星形胶质细胞P糖蛋白表达的研究

目的研究左乙拉西坦(LEV)和传统抗癫痫药(AEDs)丙戊酸钠(VPA)、卡马西平(CBZ)对大鼠皮质星形胶质细胞P-糖蛋白(P-gp)的表达的影响。方法不同浓度(1、10、50、100μg·m L-1)的VPA、CBZ及LEV持续作用于培养的正常新生鼠大脑皮质星型胶质细胞,分别在给药后10、20和30d,用免疫细胞化学法检测P-gp的表达率。结果对照组即无药物作用的正常星形胶质细胞P-gp表达率在各时点均小于5%;CBZ组100μg·m L-1在20d,30d较对照组表达增高(P0.05),20d与30d两组间比较,P0.05,其他浓度与对照组比较P0.05;VPA组100μg·m L-1在30d时较对照组表达增高(P0.05),较20d时表达增高(P0.05),其他浓度较各时点对照组比较,P0.05。LEV组在各浓度,不同时点与对照组比较差异无统计学意义(P0.05)。结论高浓度CBZ、VPA可诱导星形胶质细胞P-gp的表达,而LEV不能诱导星形胶质细胞P-gp表达。     

常用抗癫痫药对大鼠胚胎毒性的比较

对临床常用的三种抗癫痫药(AEDs)苯妥英钠(PHT)、丙戊酸内(VPA)和卡马西平(CBZ)进行胚胎毒性的比较,以期找到一种胚胎毒性较低的AEDs。用人类平均治疗量的10倍AEDs给予怀孕母鼠。孕末时,对其胎鼠进行胚胎毒性的鉴定。PHT组除了上枕骨骨化程度低于对照组外,未见其它胚胎毒性。VPA和CBZ组的胚胎毒性高于对照组。VPA组又高于CBZ组。VPA胚胎毒性最强,CBZ次之,PHT最弱。     

CYP2C19基因型对丙戊酸及其与苯妥英联合用药时血药浓度影响

目的探讨细胞色素P450 2C19(CYP2C19)基因对丙戊酸(VPA)血药浓度,以及VPA和苯妥英(PHT)联合应用时对其VPA血药浓度的影响.方法应用变性高效液相(DHPLC)技术对CYP2C19两个常见的等位基因突变进行了分析;应用荧光偏振免疫法(FPIA)测定口服抗癫痫药物患者的血药浓度.结果81例癫痫患者中CYP2C19外显子4(*3)和外显子5(*2)位点均为野生型(*1/*1)的发生率为37.0%,CYP2C19*2和CYP2C19*3的等位基因频率分别为31.5%和3.7%.单一应用VPA时,弱代谢患者较正常代谢患者的VPA血药浓度有所升高(P＜0.05).联合应用PHT和VPA可使VPA血药浓度显著降低(P＜0.01),CYP2C19正常代谢患者VPA血药浓度降低尤为明显(P＜0.01);在VPA与PHT联合用药过程中,约半数CYP2C19正常代谢患者VPA血药浓度不能达到治疗血药浓度.结论CYP2C19基因多态性影响VPA的血药浓度变化,在联合应用PHT时对VPA血药浓度的影响尤为明显,从而影响抗癫痫的临床疗效.     

抗癫药物的皮肤不良反应

癫痫(epilepsy)是中枢神经系统常见病和多发病,流行病学调查显示,其患病率约为0.70%,全球范围内约有5000万例癫痫患者。目前,抗癫痫药物(AEDs)仍是有效控制癫痫发作的主要手段,临床常用抗癫痫药物主要包括丙戊酸(VPA)、苯巴比妥(PB)、地西泮(DZP)、托吡酯(TPM)、拉莫三嗪(LTG)、左乙拉西坦(LEV)、苯妥英(PHT)、卡马西平(CBZ)、加巴喷丁(GBP)、乙琥胺(ESX)、奥卡西平(OXC)、噻加宾(TGB)和普瑞巴林(PGB)等。皮     

丙戊酸钠和卡马西平对癫痫患者血同型半胱氨酸、叶酸、维生素B12水平的影响

目的探讨丙戊酸钠(VPA)和卡马西平(CBZ)对癫痫患者血同型半胱氨酸(Hcy)、叶酸、维生素(Vit)B12水平的影响。方法检测VPA组、CBZ组、未服药组患者和正常对照组血Hcy、叶酸、VitB12浓度,并对结果进行比较。结果与未服药组及正常对照组比较,VPA组和CBZ组的血浆Hcy水平显著升高(均P<0.01),血清叶酸水平显著降低(均P<0.05);且VPA组血清VitB12水平有升高趋势,CBZ组血清VitB12水平有降低趋势,但差异均无统计学意义。结论 VPA和CBZ可引起癫痫患者的血浆Hcy水平升高和血清叶酸水平降低,对血清VitB12水平无显著影响。     

男性癫癎患者服用抗癎药物后血清甲状腺激素水平及临床意义

目的研究接受卡马西平(CBZ)、鲁米那(PB)和丙戊酸钠(VPA)单药治疗的成年男性癫(疒间)患者的甲状腺激素水平及意义.方法应用放免法测定63例男性癫(疒间)患者(22例服用CBZ,18例服用PB,23例服用VPA)及20名健康对照者血清中的总甲状腺素(TT4)、游离甲状腺素(FT4)、总三碘甲状腺原氨酸(TT3)、游离三碘甲状腺原氨酸(FT3)和促甲状腺激素(TSH)水平.结果 CBZ组TT4、FT4和FT3较对照组明显降低(均P＜0.05),TT3和TSH水平无变化;PB组的TT4和FT4较对照组明显降低(均P＜0.05),TT3、FT3和TSH水平无变化;且PB组的TT4、FT4降低程度均较CBZ组轻;VPA组各项指标均无变化.结论 CBZ、PB可通过肝酶诱导等多种途径导致甲状腺激素水平发生改变,二者的作用不完全相同;VPA对甲状腺功能无影响,有必要对服用抗(疒间)药物,尤其是CBZ患者的甲状腺激素水平进行监测.     

抗癫癎药物与大鼠海马CA1区胶质细胞TUNEL阳性表达关系的研究

目的:探讨抗癫癎药物对大鼠海马胶质细胞凋亡的影响。方法:35只60天龄SD大鼠随机分为生理盐水组(NS)、戊四氮(PTZ)组、卡马西平组(CBZ)、丙戊酸钠组(VPA)、苯妥英钠组(PHT)、托吡酯组(TPM)、拉莫三嗪组(LTG)7组,起始体重(200±20)g,戊四氮点燃其中6组制作癫癎模型,再给与抗癫癎药物治疗3周,应用TUNEL法观察大鼠海马胶质细胞的阳性表达率。结果:CA1区胶质细胞TUNEL阳性表达:NS组阳性率4.195%,PTZ组阳性率6.536%,CBZ组阳性率4.321%,VPA组阳性率5.587%,4组之间TUNEL阳性表达率差异无显著性(χ2=1.158,P>0.05);PHT组阳性率24.460%,TPM组阳性率21.605%,LTG组阳性率18.902%,三组之间TUNEL阳性表达率差异无显著性(χ2=1.378,P>0.05)。NS组、PTZ组、CBZ组、VPA组与PHT组、TPM组、LTG组之间TUNEL阳性表达率差异有显著性(χ2=70.227,P<0.005)。结论:大鼠癫癎模型经PTH、TPM、LTG治疗后,海马CA1区存在TUNEL阳性胶质细胞。     

男性癫痫患者服用抗痫药物后血清甲状腺激素水平及临床意义

目的　研究接受卡马西平 (CBZ)、鲁米那 (PB)和丙戊酸钠 (VPA)单药治疗的成年男性癫疒间 患者的甲状腺激素水平及意义。方法　应用放免法测定 6 3例男性癫疒间 患者 (2 2例服用CBZ ,18例服用PB ,2 3例服用VPA)及 2 0名健康对照者血清中的总甲状腺素 (TT4)、游离甲状腺素 (FT4)、总三碘甲状腺原氨酸 (TT3 )、游离三碘甲状腺原氨酸 (FT3 )和促甲状腺激素 (TSH)水平。结果　CBZ组TT4、FT4和FT3 较对照组明显降低 (均P<0 .0 5 ) ,TT3 和TSH水平无变化 ;PB组的TT4和FT4较对照组明显降低 (均P <0 .0 5 ) ,TT3 、FT3 和TSH水平无变化 ;且PB组的TT4、FT4降低程度均较CBZ组轻 ;VPA组各项指标均无变化。结论　CBZ、PB可通过肝酶诱导等多种途径导致甲状腺激素水平发生改变 ,二者的作用不完全相同 ;VPA对甲状腺功能无影响 ,有必要对服用抗疒间 药物 ,尤其是CBZ患者的甲状腺激素水平进行监测     

新型和传统抗癫痫药治疗新诊断癫痫患者的评价

目的评价新型和传统抗癫痫药(AEDs)单药治疗新诊断癫痫患者的疗效及安全性。方法前瞻性收集143例新诊断癫痫患者,分为卡马西平(CBZ)、丙戊酸钠(VPA)、托吡酯(TPM)和拉莫三嗪(LTG)治疗组,其中CBZ用于癫痫部分性发作,VPA用于癫痫全面性发作,而TPM和LTG用于各种类型癫痫发作,至少观察1年。采用生存分析Kaplan-Meier法比较治疗后癫痫初次发作时间、治疗失败时间,同时比较各组患者达"6月、1年无发作"比例和药物不良反应。结果 4组AEDs单药治疗后至癫痫初次发作时间、治疗失败时间的差异均无统计学意义(P0.05);CBZ、VPA、TPM和LTG组"6月无发作"率分别为80%、78%、87.9%、63.3%(均P0.05);"1年无发作"率分别为70%、66%、66.7%、50%(均P0.05)。TPM组不良反应率为63.3%,高于CBZ组(20%)、VPA组(24%)(均P0.01),而LTG组不良反应率为16.7%,与CBZ、VPA组相当(均P0.05)。结论从疗效和安全性综合考虑,新型AEDs治疗癫痫并不优于传统AEDs,其中TPM轻、中度不良反应还明显高于传统AEDs。     

Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy

BACKGROUND: Bone loss and hypovitaminosis D are reported in patients taking antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA). OBJECTIVE: To assess the relationship of VPA to bone mass and calcium metabolism in 40 adults with epilepsy on long-term VPA monotherapy, 40 age- and sex-matched epileptic patients taking phenytoin (PHT), and 40 healthy control subjects. Bone mineral density (BMD) of the second metacarpal was determined as T- and Z-scores. RESULTS: BMD reduction from control values was 14% (12% in men, 16% in women) with VPA and 13% (12% in men, 15% in women) with PHT. Among patients on VPA, nine (23%) had T-scores below -2.5 SD, suggesting osteoporosis; 15 (37%) had T-scores between -1 and -2.5 SD, suggesting osteopenia. Serum concentrations of calcium were significantly higher with VPA than in PHT or control groups. Serum concentrations of bone Gla protein (a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) associated with either drug significantly exceeded control values. Z-scores for BMD in the VPA group correlated negatively with calcium and ICTP. High ICTP correlated positively with ionized calcium, implying that increased bone resorption caused the latter. CONCLUSION: Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD.     

Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.     

Self-reported symptoms in patients on antiepileptic drugs in monotherapy

Wieshmann UC, Tan GM, Baker G. Self‐reported symptoms in patients on antiepileptic drugs in monotherapy.
Acta Neurol Scand: 2011: 124: 355–358.
© 2011 John Wiley & Sons A/S. Objective – To ascertain the frequency of self‐reported symptoms in patients taking antiepileptic drugs (AED). Methods – We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP). Results – The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self‐reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy. Conclusion – Our unblinded observational study of self‐reported symptoms suggested LTG was overall the drug with the least self‐reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies.     

A comparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients

Gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) may not be sensitive indicators of hepatocellular damage in patients taking anticonvulsant drugs as raised levels may only reflect enzyme induction. Aspartate aminotransferase (AST) is a specific, but relatively insensitive marker of liver damage and has a poor correlation with liver histology. Serum F protein is found in high concentration in the liver and levels are not influenced by enzyme induction. We measured serum F protein levels in patients taking carbamazepine (CBZ) and phenytoin (PHT) as monotherapy and in patients receiving multiple drugs. We compared the results with patients taking sodium valproate (VPA). Serum F protein levels were elevated in 6%, 22% and 13% of patients receiving CBZ, PHT and VPA, respectively. Raised GGT levels were reported for both the CBZ (26%) and PHT (78%) groups. Raised ALP levels were observed in 16%, 25% and 4% of the CBZ, PHT and VPA groups, respectively. Raised levels of serum F protein in the VPA group and the absence of any associated increases in either GGT or AST may further support the suggestion that serum F protein is an indicator of hepatocellular dysfunction associated with anticonvulsant therapy. However, further correlation with liver histology is required.     

Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism

PURPOSE: Long-term treatment with antiepileptic drugs (AEDs) is associated with increased risk of fractures. Phenytoin (PHT) and valproate (VPA) have both been suggested to influence bone health, whereas levetiracetam (LEV) is scarcely studied. The present study compares the effect of these AEDs on bone mass, biomechanical strength, and bone turnover in rats. METHODS: Female rats received PHT (50 mg/kg), VPA (300 mg/kg), or LEV (50 and 150 mg/kg) for 90 days. Dissected femurs were analyzed using dual energy x-ray absorptiometry (DXA), three-point cantilever bending, and histomorphological evaluation. Serum levels of biochemical bone turnover markers were monitored using immunoassay quantification. RESULTS: PHT and VPA reduced bone mineral density (BMD) and content (BMC) in one or more bone compartments, whereas LEV did not. VPA induced increased bone turnover, whereas modest changes were observed for PHT. Interestingly, low-dose LEV was associated with reduced biomechanical strength of the femoral neck (mainly trabecular bone). In addition, low-dose LEV treatment resulted in significantly reduced levels of serum osteocalcin, a marker of bone formation. Histomorphological analyses indicated increased retention of cartilage remnants at the growth plate metaphysis of rats treated with low-dose LEV vs. controls. CONCLUSIONS: PHT, VPA, and LEV exert differential effects on bone mass and strength, suggesting different mechanisms of action. The weakening effect of low-dose LEV on the femoral neck, despite a constant BMD, suggests a primary effect on bone quality. These findings warrant further human studies of possible adverse effects of LEV on bone development and growth, particularly in children and adolescents.     

癫痫治疗中丙戊酸钠与苯妥英钠或卡马西平的相互作用

丙戊酸钠与苯妥英钠或卡马西平合用治疗各型癫痫90例,丙戊酸钠使苯妥英钠和卡马西平血浓度下降;丙戊酸钠和卡马西平是强有力的肝酶诱导剂,使丙戊酸钠血浓度降低。抗痫药之间的相互作用错综复杂,临床上选择单一用药,尽量避免联合用药。     

Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): differentiation of levetiracetam from conventional antiepileptic drugs

PURPOSE: Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures. METHODS: The effect of single (40, 80, and 160 mg/kg, i.p.) and 5-day (80 mg/kg/day, i.p.) administration of LEV on tonic convulsions and absence-like seizures in SERs were studied. Tonic convulsions induced by blowing air onto the animal's head at 5-min intervals for 30 min and spontaneous absence-like seizures characterized by 5- to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG were recorded for 30 min. In the single-administration study, observations for seizure activity were performed once before and 3 times (45, 75, and 135 min) after drug administration. In the 5-day administration study, seizure observation was performed 4 times for 30 min (once before and 3 times after drug administration) during the 5-day drug-administration period, and continued once a day until 8 days after the final administration. The antiepileptic effects of 5-day administration of conventional AEDs (PHT, PB, VPA, and CBZ) were examined by using similar methods. RESULTS: Tonic convulsions and absence-like seizures were inhibited by a single administration of LEV at 80 and 160 mg/kg, i.p., but not significantly at 40 mg/kg, i.p. When LEV was repeatedly administered at 80 mg/kg/day, i.p., for 5 days to SERs, the inhibitory effects on seizures increased with administration time. The number of tonic convulsions and absence-like seizures were significantly reduced to 39.1% and 38.4% compared with previous values, respectively, after 5-day LEV administration. Furthermore, significant inhibition of tonic convulsions was detected 相似文献   

Anticonvulsant properties of the novel nootropic agent nefiracetam in seizure models of mice and rats

PURPOSE: Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy. METHODS: The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test. RESULTS: NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models. CONCLUSIONS: These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.     

抗癫痫药物对癫痫患者甲状腺激素水平影响的研究

目的 研究癫痫患者甲状腺激素水平和抗癫痫药物对其影响以及与疗效之间的关系。方法 测定已确诊的45例未服用过抗癫痫药物的癫痫患者血清甲状腺激素水平并与30例健康对照组进行比较。再经卡马西平、苯妥英钠、丙戊酸钠三种抗癫痫药物分组单药治疗3个月、6个月、年后观察甲状腺激素水平的变化及与疗效之间的关系。结果 未服用抗癫痫药物的新诊断癫痫患者游离甲状腺素（FT4）水平显著低于健康对照组,经苯妥英钠、卡马西平分别治疗3个月、6个月、1年后T4、FT4、FT3显著低于治疗前水平,TSH无显著性变化。经丙戊酸钠治疗后的不同时间段各甲状腺激素水平与治疗前比较无显著性差异（P＞0．05）。甲状腺激素水平的变化与化疗效之间似无相关性。结论 癫痫的反复发作虽未经抗癫痫药物治疗已存在FT4水平的降低。苯妥英钠、卡马西平可明显造成癫痫患者的亚临床甲状腺功能降低（T4、FT4、FT3下降）,丙戊酸钠对患者甲状腺激素水平无显著影响。甲状腺激素水平的变化与疗效之间无相关性。