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。     

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     

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.     

奥氮平对甲状腺激素水平的影响

目的：了解奥氮平对精神分裂症患者甲状腺素水平的影响。方法：随机抽取正在服用奥氮平的住院精神分裂症患者20例,分别于入组时、入组后1个月查FT3、FT4、TSH并进行比较。结果：入组时与常模比较FT3显著下降（P〈0．01）;1个月后与常模比较FT3、FT4显著下降（P〈0．01）;入组时与1个月后比较FT4显著下降（P〈0．01）;TSH与年龄、剂量、服用时间正相关（r〉0．3）;FIB、FT4、TSH与性别无相关性。结论：奥氮平可致甲状腺激素水平下降,TSH有反馈性升高趋势,但尚在正常范围内。临床或许可以通过干预甲状腺激素水平来调整精神分裂症患者的情绪障碍。     

齐拉西酮对首发与慢性女性精神分裂症甲状腺激素水平的影响

目的探讨齐拉西酮对女性精神分裂症住院患者甲状腺激素的影响及首发与慢性患者（病程≥5年）的差异。方法随机抽取女性精神分裂症患者64例（首发组30例,慢性组34例）,均用齐拉西酮治疗,于治疗前和治疗8周末测定甲状腺激素。对照组为30例正常健康女性。结果治疗前慢性组T3、TSH低于对照组,有显著性差异（P〈0.05）。齐拉西酮治疗后慢性组T4水平明显下降,而TSH水平则明显升高,且有显著性差异（P〈0.05）;首发组治疗前后无显著性差异。结论慢性精神分裂症患者存在甲状腺功能异常。齐拉西酮治疗可降低慢性精神分裂症患者血清甲状腺素T4水平,升高促甲状腺素（TSH）水平;对三碘甲腺原氨酸T3、游离三碘甲腺原氨酸FT3、游离甲状腺素FT4无明显影响;首发与慢性患者无显著性差异。     

托吡酯长期治疗对成年癫疒间患者血清甲状腺激素水平的影响

目的 探讨托吡酯(TPM)长期治疗对成年癫疒间患者血清甲状腺激素水平的影响.方法 用化学发光分析法测定成年癫疒间组患者(32例)TPM治疗前、后的血清甲状腺激素水平,并与健康对照组(40人)进行比较. 结果治疗前成年癫疒间组患者甲状腺激素水平与健康对照组比较无统计学意义(均P>0.05);TPM治疗后3个月、6个月、12个月及24个月的甲状腺激素水平与治疗前及健康对照组比较差异亦无统计学意义(均P>0.05).结论 TPM短期与长期治疗对成年癫疒间患者的甲状腺激素水平没有影响.     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

哌罗匹隆与奋乃静治疗精神分裂症患者60例对照研究

目的：总结分析哌罗匹隆与奋乃静在精神分裂症患者治疗中的疗效差异。方法选择2010-06-2012-11我院收治的60例精神分裂症患者为研究对象,随机分为观察组和对照组各30例,观察组患者给予哌罗匹隆治疗,对照组给予奋乃静治疗,比较2组疗效,同时监测2组患者PRL（血清催乳素）、TSH（促甲状腺激素）、T3（三碘甲状腺原氨酸）、FT3（游离T3）、T4（甲状腺素）、FT4（游离T4）。结果观察组有效率80·00％高于对照组76·67％,差异无统计学意义（P＞0·05）;2组患者PANSS总分和各因子评分都明显优于治疗前（P＜0·05）;治疗后2组TESS评分差异无统计学意义（P＞0·05）。结论哌罗匹隆与奋乃静对精神分裂症患者治疗疗效相当,但哌罗匹隆对患者PRL和T4影响较小,且用药依从性较好。     

女性抑郁症患者血清甲状腺激素水平研究

目的:探讨女性血清甲状腺激素水平与抑郁症的关系.方法:采用免疫化学发光法对58例女性抑郁症患者及对照组40例健康女性的血清游离三碘甲状腺原氨酸(FT3),游离甲状腺素(FT4),促甲状腺素(75H)进行了检测.结果:女性抑郁症患者治疗前血清FP4,TSH较对照组低(P均<0.01),而FT3与对照组差异无显著性(P>0...     

西比灵辅助治疗癫痫的疗效及其对脑脊液钙含量的影响

目的 观察西比灵辅助治疗癫痫的疗效，及对脑脊液钙含量的影响。方法 将64例癫痫病人随机分为西比灵组及对照组32例。两组按不 发作类型分别应用抗癫痫药物治疗。西比灵组加西比灵每晚5mg，2周内加至每晚10mg，连服3个月。观察治疗前，后癫痫发作频率及癫痫发作后3小时，72小时脑脊液Ca^2 含量。结果 西比灵组总有效率有75％，对照组为50％，两组有显著差异（P＜0．05）。癫痫发作后3小时脑脊液Ca^2 含量明显低于健康组（P＜0．01），发作后72小时西比灵组已恢复到健康组水平（P＞0．05），而对照组仍低于健康组（P＜0．01）。结论 西比灵配合抗癫痫药物治疗，能减少癫痫患者的发作频率，并能迅速恢复癫痫病人脑脊液Ca^2 浓度。     

Serum Steroid Hormones and Pituitary Function in Female Epileptic Patients During Carbamazepine Therapy

Ten regularly menstruating women with epilepsy were studied in a 12-month prospective follow-up study to evaluate the short-term effects of carbamazepine (CBZ) on serum sex hormone balance and pituitary function. Thirteen female epilepsy patients receiving long-term CBZ monotherapy (mean medication duration 5.3 years) were also studied. Controls were 17 regularly menstruating healthy volunteers. Untreated patients had higher free testosterone (FT) and luteinizing hormone (LH) serum concentrations than control subjects, whereas the other parameters did not differ between these two groups. However, serum sex hormone binding globulin (SHBG) levels increased and dehydroepiandrosterone sulfate (DHEAS) levels decreased during CBZ treatment. Although calculated free androgen index (FAI) decreased during CBZ therapy, the directly measured FT levels remained unaltered. These changes were found after 2 months and continued after 12 months of CBZ treatment. Moreover, patients with long-term CBZ also had high SHBG levels, low serum DHEAS levels, and low FAI values. Basal LH serum levels decreased during the first year of CBZ treatment and luteinizing hormone-releasing hormone (LH-RH)-stimulated LH concentrations were lower after 2 months of CBZ treatment. Although the serum basal follicle-stimulating hormone (FSH) and prolactin (PRL) levels were unaffected during the first year of CBZ therapy, the LH-RH-stimulated FSH concentrations and metoclopramide (MC)-stimulated PRL concentrations were lower after 12 months of CBZ treatment than before CBZ. Both basal and stimulated gonadotropin and PRL serum levels of long-term CBZ patients were unaffected. No changes were found in estradiol (E2), testosterone (T), or cortisol (C) serum concentrations during short or long-term CBZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

拉莫三嗪对癫(癎)患者血清甲状腺激素水平的影响

目的 观察拉莫三嗪对癫(癎)患者血清甲状腺激素水平的影响.方法 用化学发光分析法检测51例癫(癎)患者(癫(癎)组)拉莫三嗪治疗前及治疗后3个月、6个月、12个月的血清甲状腺激素水平,并与43名正常对照者进行比较.结果 癫(癎)组患者治疗前血清甲状腺激素水平与正常对照组比较,差异均无统计学意义;拉莫三嗪治疗后3个月、6个月、12个月的甲状腺激素水平与治疗前及正常对照组比较,差异亦均无统计学意义.结论 拉莫三嗪对癫(癎)患者的甲状腺激素水平没有明显影响,安全性好.     

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.     

Metabolic and hormonal disturbances in women with epilepsy on antiepileptic drug monotherapy

PURPOSE: Women with epilepsy (WWE) tend to have hormonal and metabolic abnormalities, raising concerns about an increased risk of cardiovascular disorders. This study was performed to determine whether epilepsy itself and/or antiepileptic drug (AED) medication cause metabolic abnormalities. METHODS: WWE in premenopausal state aged 18 to 45 years old, currently on AED monotherapy for more than six months, were recruited for this study. The subjects checked their oral temperature each morning, and tested serum levels for lipid profiles, insulin, glucose, and leptin. A HOMA-index was used as a marker for insulin resistance. RESULTS: Of the 54 total patients, 18 women were diagnosed with primary generalized epilepsy (PGE) and the other 36 were diagnosed with localization-related epilepsy (LRE). Among the subjects, 19 women were on carbamazepine (CBZ), 12 on valproate (VPA), 12 on lamotrigine (LTG), and 11 on topiramate (TPM). Body mass index increased and HDL-cholesterol decreased in patients on VPA monotherapy compared with CBZ, LTG, or TPM (p=0.046 and 0.002). Metabolic syndrome was more frequently associated with VPA-treated patients (41.7%) than CBZ (5.3%), LTG (0%), or TPM group (0%) (p=0.005). There were no differences in hormonal and metabolic indices between PGE and LRE groups. CONCLUSIONS: WWE on VPA monotherapy are more obese and more frequently suffer from metabolic syndrome. LTG or TPM may be safer when prescribed to the patients with high risk of cardiovascular disease.     

Steady-State Pharmacokinetics of Topiramate and Carbamazepine in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Summary: Purpose: We studied the steady-state pharmacokinetic profile of topiramate (TPM) as a function of dose and the effects of comedication with carbamazepine (CBZ). Methods: We enrolled 12 patients with partial epilepsy receiving chronic stable doses of CBZ 300–800 mg every 8 h. In a 6-week period, TPM was added and doses were increased at -2-week intervals from 100 to 200 to 400 mg every 12 h and stabilized at the highest tolerated dose to as high as 400 mg every 12 h. CBZ was tapered in the next 4 weeks when possible, and TPM was maintained as monotherapy at the highest stabilized dose for 2 more weeks. Plasma and urine samples were collected before TPM dosing, after each TPM dose increase, and during TPM monotherapy. Results: Dose-normalized results (n = 10) for TPM area under the curve from 0 to 12 h (AUC_(0–12)), C_min(0), and C_avg indicated that TPM exhibits linear plasma pharmacokinetics over the dose range of 100- to 400-mg every 12 h when administered with CBZ. Mean TPM AUC_(0–12)) C_max, C_min(0), and C_avg values were -40% lower during CBZ treatment as compared with those during TPM monotherapy (n = 3). TPM oral and nonrenal clearance rates were approximately two- to threefold higher, whereas TPM renal clearance was unchanged during concomitant CBZ treatment (n = 3). There were no significant changes in total and unbound CBZ and CBZ-epoxide (CBZ-E) pharmacokinetics during TPM administration (n = 10). TPM pharmacokinetics during concomitant CBZ treatment were significantly different from those during TPM monotherapy, suggesting that metabolic clearance of TPM increases when CBZ is coadministered. Conclusions: When CBZ is reduced or discontinued, TPM doses may need to be lowered to maintain equivalent plasma concentrations. Adjusting the CBZ dose for pharmacokinetic reasons when TPM is administered as adjunctive treatment does not appear to be necessary.     

Conversion from carbamazepine or oxcarbazepine to topiramate in adolescents and adults with epilepsy

Objective – To explore effectiveness, tolerability and changes in quality of life in patients with epilepsy converting to topiramate (TPM) from carbamazepine (CBZ) or oxcarbazepine (OXC) due to insufficient effectiveness and/or tolerability. Methods – A multicenter, open‐label, non‐interventional trial was used to examine patients (≥ 12 years) with epilepsy, changing to TPM monotherapy from baseline mono‐ or combination therapy with CBZ or OXC. TPM was added to the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1–2 weeks, until a final dose between 50 and 200 mg/day was reached. On the basis of clinical judgment, the treating physician decided whether or not the existing AED treatment with CBZ or OXC could then be withdrawn. Type and number of seizures, preferred TPM dose, quality of life (QOLIE‐10 questionnaire), subjective perception of improvement and adverse events (AE) were documented. Results – 140 patients (53.5% women, mean age 47 years) decided to switch to TPM due to insufficient effectiveness (75% of patients) and/or poor tolerability (80%) of the CBZ/OXC treatment. Average duration of follow‐up was 24 weeks with an overall discontinuation rate of 19.3%, mainly due to AEs (12.1%). At study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/day. A seizure reduction of ≥ 50% was achieved in 91% of patients in the last scheduled period (weeks 12–26); 62% of patients entering that period remained seizure free. Quality of life at endpoint improved significantly when compared with baseline for all domains of QOLIE‐10 (P < 0.001). Most frequent AEs (reported by ≥ 5% of patients) were paresthesia (9.3%), weight loss (7.9%), convulsions (5.7%) and memory disorders (5.0%). Conclusion – In patients with epilepsy, previously not satisfactorily treated with CBZ or OXC, conversion to TPM may result in an improvement in seizure control as well as in quality of life.     

Thyroid and Myocardial Function After Replacement of Carbamazepine by Oxcarbazepine

Summary: We determined changes in serum concentrations of thyroid hormones during carbamazepine (CBZ) therapy during a 5-year prospective follow-up study of 20 patients with newly diagnosed epilepsy. In addition, we evaluated the effects of replacing CBZ with oxcarbazepine (OCBZ) in 12 male patients with epilepsy in a 6-month prospective follow-up study. Circulating thyroxine and free thyroxine levels decreased after 2-month CBZ treatment and remained at a low level during the 5-year follow-up. There were no associated changes in serum thyrotropin (TSH) concentrations. When CBZ was replaced by OCBZ, the function of the liver's P450 enzyme system normalized, as shown by an increase in antipyrine_T1/2, and a decrease in antipyrine_CL. Serum total and free thyroxine levels increased, and thereafter serum TSH levels decreased. Indexes of diastolic heart function improved concomitantly, which may reflect subclinical hypothyroidism at the cellular level during CBZ treatment. We conclude that normal thyroid function can be restored in patients with epilepsy by replacing CBZ with OCBZ.     

Carbamazepine, Phenytoin, Sex Hormones, and Sexual Function in Men with Epilepsy

Summary We evaluated the effects of carbamazepine (CBZ) on serum androgen levels and sexual function prospectively for 5 years in 11 men with epilepsy and in 25 patients receiving either CBZ (14 patients) or phenytoin (PHT) (11) monotherapy for >5 years. Serum sex hormone binding globulin (SHBG) levels increased and free androgen index (FAI) decreased during CBZ treatment, and these changes correlated with duration of CBZ therapy. Similarly, serum SHBG levels increased and FA1 values decreased in patients receiving PHT for >5 years. CBZ and PHT increase serum SHBG levels, leading to decreased FAI. These drugrelated hormonal changes may be the primary cause of hyposexuality common in men with epilepsy.