小剂量拉莫三嗪与丙戊酸合用治疗成人癫痫临床观察

目的 研究小剂量拉莫三嗪与丙戊酸合用治疗成年人各种类型癫痫的有效件和安全性.方法 对100例成年癫痫患者采用逐步增量的方法给予拉莫三嗪至每目100 mg,加约期4周,并继续服用原剂量的丙戊酸治疗,连续观察6月,记录患者发作的情况及不良反应.结果 小剂量拉其三嗪与丙戊酸合用总有效率为77.2%,完全控制50.O%,各种类型发作之间疗效比较差异无显著性(χ2=1.37,P>0.05);各型癫痫在人组4～6个月后较入组前3个月发作频率均减少,差异有显著性(P<0.05).不良反应发生率23.7%,与入组前后小良反应发牛率相比无显著变化(χ2=0.21,P>0.05).结论 小剂量托莫二三嗪与丙戊酸合用治疗成年人各种类犁癫痫均取得良好疗效,不良反应无增加.     

中国成年人拉莫三嗪药代动力学及丙戊酸对其影响

目的研究中国人拉莫三嗪药代动力学特点及丙戊酸的影响。方法4例健康志愿者服拉莫三嗪100 mg后0.5、1、1.5、2、2.5、3、3.5、4、6、8、10、12、15、24、36、48 h分别采血样。连续每天服丙戊酸1.0、0.6、0.3 g 7 d后再进行同样的拉莫三嗪的血液药物代谢动力学实验。用HPLC法测定拉莫三嗪及丙戊酸血药浓度,NDST药物动力学程序包拟合及SPSS 10.1软件统计学处理。结果拉莫三嗪的药物代谢动力学属一级动力学两房室模型。拉莫三嗪血药浓度峰值在2 h以内出现,平均清除率(2.00±0.39)L/h、半衰期(37.5±7.0)h。合并丙戊酸后,拉莫三嗪达峰时间及房室模型无变化;当丙戊酸血药浓度低于(54.55±9.53)μg/ml时,随丙戊酸血药浓的增加,拉莫三嗪的半衰期延长、清除率下降、血药浓度明显增加,呈线性相关。当丙戊酸血药浓度在超过此点,3种参数无进一步改变的趋势。当丙戊酸血药浓度在(98.36±23.59)μg/ml时,拉莫三嗪的半衰期为(89.95±18.19)h,丙戊酸对拉莫三嗪的峰浓度出现的时间及房室模型无影响。结论在丙戊酸的有效治疗浓度范围内,拉莫三嗪药物代谢动力学参数变化无进一步改变的趋势。     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

Adding Lamotrigine to Valproate: Incidence of Rash and Other Adverse Effects

PURPOSE: Valproate (VPA) triples the half-life of lamotrigine (LTG), and combined use may be difficult. The adverse effect (AE) profile of this combination needs clarification. METHODS: We prospectively recorded our experience in adding LTG to VPA-containing regimens in 108 patients. Data collected included medications, seizure types and syndromes, and AEs. Patients were followed up to 27 months, until a stable dose was reached, or until LTG was discontinued. Patient management was not altered by this study. There were 60 patients with partial-onset seizures, 30 with generalized onset, and 12 with the Lennox-Gastaut syndrome. In 37, LTG was added to VPA monotherapy, and in 71, to VPA and other drugs. The median starting dose of LTG in our adult patients was 20.8 mg/day. RESULTS: LTG was added successfully in 86 (80%) patients. It was discontinued in 22 (20%): seven because of rash, seven for other AEs, and nine for other reasons. Rash occurred in 14 (13%) but caused discontinuation of LTG in only seven. We found a rash rate of 14.2% and a discontinuation rate because of rash of 8.7% among 310 patients in whom LTG was added to drug regimens not including VPA. Other AEs included fatigue (12%), gastrointestinal (GI) symptoms (9%), dizziness, headache, and insomnia (3% each). Serious AEs were hallucinations (two patients), hepatic enzyme elevations (two patients), irritability (one patient), and low white blood cell count (one patient). Whether LTG was added to VPA monotherapy or polytherapy made no difference in overall AE rate. CONCLUSIONS: LTG can be added to VPA with an acceptable incidence of side effects. LTG-induced rashes are no more common with VPA than with other drugs when LTG is added at very low initial dosages. Rashes are potentially serious and should be evaluated promptly.     

Lupus anticoagulant induced by the combination of valproate and lamotrigine

A 5-year-old boy with generalized absence seizures was treated with valproate (VPA), 30 mg/kg/day. One month after VPA introduction, routine examination showed moderate reduction in fibrinogen and prolonged partial thromboplastin time (PTT). The search for lupus anticoagulant (LAC) was negative. After 10 months of VPA treatment, seizures persisted, and lamotrigine (LTG), 2 mg/kg/day, was progressively given with VPA. Seizures disappeared, but PTT was more prolonged than before LTG introduction. The search for LAC was positive, and enzyme-linked immunosorbent assays (ELISAs) for immunoglobulin G (IgG) anticardiolipid antibodies were positive. Serum autoantibody screen and rheumatoid factor were negative; serum complement was normal. LAC eventually disappeared with VPA discontinuation. We believe that LTG may have exacerbated an initially mild immune response induced by VPA without clinical evidence of systemic disease. We therefore suggest that careful surveillance for LAC and systemic disease should be instituted when VPA is used with LTG.     

拉莫三嗪治疗成人部分性发作癫癎的临床疗效与安全性研究

目的评价拉莫三嗪治疗成人部分性发作癫癎的临床疗效与安全性。方法收集成人部分性发作癫癎患者89（76）例,分别给予拉莫三嗪单药、替换或添加治疗,进行开放性自身对照研究,随访24周发作情况,登记监测不良反应。结果 89例中76例完成终点试验,总有效率为82.8%,平均起效剂量为（99.7±18.6）mg/d,平均起效时间为（17.8±5.4）d,保留率为85.39%。不良反应发生率为15.8%,皮疹发生率为2.2%。结论拉莫三嗪是一种安全、有效的抗癫癎药物。     

The Efficacy of Valproate-Lamotrigine Comedication in Refractory Complex Partial Seizures: Evidence for a Pharmacodynamic Interaction

PURPOSE: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs). METHODS: After a 3-month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add-on treatments with VPA, LTG, or their combination, according to an open, response-conditional, crossover design. Each period consisted of a 6- to 12-week dose optimization followed by 3-month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next. RESULTS: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62-78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA--LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration. CONCLUSIONS: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects.     

The Efficacy of Lamotrigine in Children and Adolescents with Refractory Generalized Epilepsy: A Randomized, Double-Blind, Crossover Study

Summary: Purpose: We report a double-blind, placebo-controlled crossover study of lamotrigine (LTG) as add-on treatment in therapy-resistant, generalized epilepsy in children and adolescents (n = 30).
Methods: Twenty patients had Lennox-Gastaut syndrome. Each patient acted as his or her own control. LTG and placebo were randomly added to existing antiepileptic medication (AEDs). The LTG dosage was individualized in an open phase preceding the placebo/treatment phase. Patients who responded to LTG in the open phase went on to the double-blind phase. "Responders" were defined as patients with a >50% seizure reduction or less severe seizures or both, or improved behavior or improved motor skills or both. "Nonresponders" were defined as children who showed no positive effects of LTG with plasma levels of 10 μg/ml or children who had adverse events during the open phase.
Results: There was a clear statistically significant reduction of seizure frequency in LTG compared with placebo treatment. None of the children studied showed abnormal biochemical or hematologic findings, or changes in plasma levels of concomitantly administered AEDs.
Conclusions: LTG is a well-tolerated and effective treatment in children with intractable generalized epilepsies, including those with Lennox-Gastaut syndrome. The study design allowed a double-blind placebo-controlled assessment of LTG although the participating children used 19 different AED combinations at entry.     

丙戊酸钠单药治疗新诊断儿童全面性癫痫失败原因分析

目的 探讨丙戊酸钠单药治疗新诊断儿童全面性癫痫失败原因、影响因素。方法 前瞻性、开放性收集新诊断全面性癫痫病例,均接受丙戊酸钠单药治疗,随访到治疗2年以后。根据疗效分为对照组与疗效差2组,收集一般临床资料、脑电图等,采用Logistic回归分析治疗失败原因。结果 231例患儿完成本研究,2年时有62例因疗效差而改用其他药物,169例患儿疗效可,3例依从性差,1例因副作用改药。两组脑电图异常率(疗效差组90.32%vs.对照组61.54%),头颅MRI异常率(疗效差组45.16%vs.对照组23.08%),首次发病年龄{疗效差组0.50(0.42,2.50)岁vs.对照组0.75(1.50,5.16)}岁等比较有统计学意义(P0.05)。单因素分析发现智能是否正常、出生窒息史、头颅MRI异常、首次发作年龄等有统计学意义(P0.05)。进一步多因素回归分析发现首发年龄低(OR=2.124,P=0.004)、智能障碍(OR=10.535,P=0.000),头颅MRI异常(OR=1.603,P=0.020),出生时有窒息(OR=1.913,P=0.027)为丙戊酸钠治疗全面性癫痫疗效差的独立危险因素。结论 丙戊酸钠单药治疗全面性癫痫失败主要原因为疗效差,其次为依从性差、不良反应等。疗效差风险因素有首发年龄低、智能障碍、头颅MRI异常及出生时有窒息等。     

Lamotrigine in Treatment of 120 Children with Epilepsy

Summary: One hundred twenty children aged 10 months to 16 years 9 months were included in three studies with lamotrigine (LTG): a single-blind study (n = 60), a pharmacokinetic study (n = 23), and a compassionate group (n = 37). At 3 months, 11 patients had become seizure-free and 34 had >50% decrease in seizure frequency. The best results involved absence epilepsy, Lennox-Gastaut syndrome (LGS), and other symptomatic generalized epilepsy. Forty-two patients were followed > 1 year, 22 for a mean of 2.2 years, and there was no significant increase in seizure frequency as compared with 3-month follow-up. Fourteen patients became seizure-free for >6 months; all except 1 had generalized epilepsy. For 12 patients, treatment could be reduced to monotherapy, but for those with valproate (VPA) comedication LTG dosage had to be increased; 25% of patients with VPA monotherapy exhibited skin rash, appearing 3–18 days after starting LTG. For 4 patients, LTG could be reintroduced after VPA was withdrawn. Ten patients had ataxia and/or drowsiness and 2 had vomiting. For all other patients, tolerance was excellent.     

Male infertility: possible association with valproate exposure

PURPOSE: To describe a potential association between male infertility and valproate (VPA) exposure. VPA has been implicated in the development of polycystic ovarian disease and subsequent menstrual and infertility problems in women with epilepsy. Infertility has been well described in population-based studies of persons with epilepsy. The low marital rates for men with epilepsy have previously been thought to play a major contributing role. METHODS: We report a case of a 32-year-old man whose wife and he were able to bear a child before the development of his epilepsy. With VPA monotherapy, the family were unable to conceive despite 4 years of unprotected intercourse. An infertility evaluation of the man revealed a very low sperm count of < 50,000/ml, no motile sperm, < 10% viability, and 100% with abnormal structure. Follicle-stimulating hormone, luteinizing hormone, and testosterone levels were normal. RESULTS: Felbamate (FBM) was initiated and VPA discontinued for improved seizure control. Within 4 months, the couple conceived their second child. A seminal analysis revealed a sperm count of > 16 million, 50% motility, 78% viability, and 72% with abnormal structure. CONCLUSIONS: One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of VPA on spermatic structure and function.     

Lamotrigine in Pregnancy and Lactation: A Case Report

Summary: Purpose: We investigated the effect of pregnancy on the kinetics of lamotrigine (LTG), passage of LTG over the placenta and the excretion of the drug in breast milk.
Methods : We used high-performance liquid chromatography to determine concentrations of LTG in plasma and in breast milk in a woman who was treated with LTG monotherapy during pregnancy and lactation.
Results : Plasma levels of LTG decreased as pregancy progressed. The ratio of dose to plasma concentration was 5.8 times higher at delivery and 3.6 times higher in late pregnancy as compared with 5 months postpartum, suggesting enhanced clearance of LTG during pregnancy. The concentration ratio of umbilical cord to mother's plasma was 1.2 indicating extensive passage of LTG over the placenta. The LTG plasma concentration in the newborn was still 48 h after birth similar to the plasma levels of the mother at delivery and in the umbilical cord. The ratio of milk to plasma concentration was 0.6 2 weeks after delivery and the plasma concentration in the breastfed child was 25% of the mother's plasma levels. No adverse effects were observed in the newborn.
Conclusions : The kinetics of LTG may be influenced by pregnancy to such a degree that dose adjustments may be indicated. Due to an extensive passage of LTG into breast milk, and a slow elimination in the newborn, LTG concentrations in the nursed infant may reach levels at which pharmacological effects can be expected.     

The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate

PURPOSE: The aim of this study was to evaluate the effects of short-term oxcarbazepine (OXC) and valproate (VPA) monotherapy on thyroid functions in children. METHODS: Fifty-five newly diagnosed epileptic children with normal thyroid functions (confirmed with the thyrotropin releasing hormone stimulation test) participated in this study. VPA treatment was started in 30 patients and OXC in 25 patients. Serum thyroxine (T(4)), free thyroxine (fT(4)), triiodothyronine (T(3)), free triiodothyronine (fT(3)), reverse T3 (rT(3)), thyroid peroxidase antibodies (TPO-ab), and urine iodine levels were evaluated at baseline and at the third and sixth months of therapy. RESULTS: In the OXC group, serum T(4), fT(4), T(3), fT(3), and rT(3) levels were found to be decreased at the third and sixth months, the differences were significant compared to the baseline values except for fT(3) levels at the third month and fT(4) and rT(3) levels at the sixth month (p < 0.05). At the sixth month, serum T(4) level dropped below the normal reference value in 8 (32%), fT(4) in 5 (20%), T(3) in 4 (16%), and fT(3) in 3 (12%) patients. In the VPA group, mean T(4), fT(4), T(3), fT(3), and rT(3) levels at 3 and 6 months remained similar compared to the baseline values (p > 0.05). Mean serum thyroid stimulating hormone levels increased significantly at the sixth month compared to the baseline values in the VPA group (p < 0.05) while it remained unchanged in the OXC group (p > 0.05). There was no effect of either drug on urinary iodine excretion and serum TPO-ab levels remained in normal ranges throughout the study. CONCLUSIONS: In this prospective study, it is documented that children under short-term OXC or VPA therapy showed altered thyroid functions similar to the changes observed after long-term treatment. Although, the clinical significance of these results need to be evaluated with future studies, this observation of altered thyroid functions points out that thyroid functions may need to be monitored closely in children receiving antiepileptic treatment, even in the short-time interval.     

Lamotrigine Therapy in Juvenile Neuronal Ceroid Lipofuscinosis

PURPOSE: To evaluate the effects of lamotrigine (LTG) therapy on epileptic seizures and general well-being in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: LTG was initiated in 28 patients with JNCL. The mean age of the patients at the initiation of LTG was 13.7 years (range, 6.7-28.2 years). LTG was started at a dosage of 0.1-0.5 mg/kg/day and increased every 2 weeks until a maintenance dose of 1.25-15 mg/kg/day was reached. On the basis of the indication for LTG therapy, the patients could be divided into four groups. In the first group, LTG was initiated on an add-on basis; in the second group, LTG was started as the first antiepileptic drug (AED) because of seizures, and in the third group, despite no preceding seizures, because of epileptiform activity in the whole-night polysomnography; in the fourth group, LTG replaced valproate (VPA), which was discontinued because of adverse side effects. The efficacy was assessed after 1 year on LTG. The mean follow-up time was 2.8 years (range, 1.3-5.8). RESULTS: LTG had a favorable effect in 23 of 28 patients. A decrease in frequency of seizures of > or =50% was observed in 10 and a decrease in severity of seizures in nine of the 22 patients who had preceding seizures. Increases in well-being were found in 18 of 28. During the follow-up, LTG was continued as monotherapy in 13 of 19 patients. CONCLUSIONS: In light of our experiences, LTG seems to be a valuable drug in JNCL.     

Concentration-Effect and Concentration-Toxicity Relations with Lamotrigine: A Prospective Study

Summary: This prospective study was designed to ascertain whether measurement of lamotrigine (LTG) concentrations in the epilepsy clinic could be used to predict the onset of complete seizure control or the emergence of adverse effects. LTG was initiated in doses of 25 or 50 mg daily in 69 patients with newly diagnosed or poorly controlled epilepsy and was increased monthly in 50–mg increments until the patient became seizure-free for at least 6 months or developed adverse effects that abated after a reduction in dosage. LTG and other antiepileptic drug (AED) concentrations were measured at each clinic visit but were not supplied to the investigator examining the patients. Overall, 19 patients either withdrew due to lack of efficacy or defaulted from the clinic. Of the remaining 50 patients, 32 (19 monotherapy, 13 polytherapy) became seizure-free at widely varying daily LTG doses (median 200 mg, range 25–850 mg) and concentrations (median 3.8 mg/L, range 1.4–18.7 mg/L). Likewise, the 18 patients (5 monotherapy, 13 polytherapy) who experienced intolerable side effects showed substantial variations in daily LTG doses (median 300 mg, range 100–900 mg) and concentrations (median 4.0 mg/L, range 0.4–18.5 mg/L). No useful concentration-effect or concentration-toxicity relation with LTG could be demonstrated in this study; therefore, we believe that routine therapeutic drug monitoring with this new AED is not currently indicated.     

Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication

Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty‐one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age‐matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow‐up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T₄), 70.2; SD, 10.9 nM; and free thyroxine (FT₄), 11.5; SD, 1.8 pM] or OXC (T₄, 74.9; SD, 16.4 nM; and FT₄, 11.3; SD, 1.8 pM) than in the control girls (T₄, 96.6; SD, 15.1 nM, and FT₄, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty‐three% of the girls taking CBZ and 67% of the girls taking OXC had serum T₄ and/or FT₄ levels below the lower limit of the reference range. The VPA‐treated girls with epilepsy had normal serum T₄ and FT₄ concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication.     

拉莫三嗪治疗儿童癫痫合并注意障碍伴多动的自身对照研究

目的探讨拉莫三嗪对儿童癫痫合并注意障碍伴多动的治疗效果。方法对拉莫三嗪(LTG)治疗癫痫合并注意障碍伴多动(ADHD)的患儿进行开放性自身对照临床试验,治疗期为1~2年。结果ADHD症状好转者9例,有效率为75%;癫痫发作频度减少≥50%,10例(83%),EEG好转率为75%。结论LTG治疗儿童癫痫合并ADHD是有效的。     

Adverse effects of carbamazepine,phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients

Objective

Antiepileptic drugs (AEDs) have been widely used in patients with epilepsy but the adverse effects in adult Chinese patients have not been investigated. This study evaluated the adverse effects of four commonly prescribed AED monotherapies with carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) in adult Chinese patients with epilepsy.

Methods

The prospective open-label clinical trial was conducted at the Chongqing Epilepsy Center. The study enrolled 505 adults with newly diagnosed epilepsy, including generalized tonic–clonic (n = 110), partial and partial secondarily generalized (n = 395) seizures. Patients were evaluated by two clinicians at the Center and were prescribed one type of AED monotherapy with CBZ, PHT, VPA or LTG for a 24-month period. An adverse effect profile, as well as efficacy of monotherapy, was obtained through a face-to-face interview with the patient at each visit. A physical examination and routine laboratory tests were performed during a clinical screening.

Results

A total of 62.6% (316/505) patients successfully completed the AED monotherapy study: 64.3% of those receiving CBZ, 55.9%—PHT, 61.5%—VPA, and 66.2%—LTG. However, 34.7% of the patients discontinued the AED monotherapy because of unsatisfactory seizure control. Overall, 18% of patients experienced adverse effects: for CBZ (25/168; 14.9%), PHT (18/59; 30.5%), VPA (32/192; 16.7%) and LTG (16/86; 18.6%). The most common drug-related adverse events included gastrointestinal disturbances, loss of appetite and nausea, weight gain and fatigue/tiredness. Tremor and nystagmus occurred in some patients receiving PHT and VPA. Two CBZ, one PHT and four LTG patients (n = 7) discontinued the study due to rash.

Conclusion

Adult Chinese patients with epilepsy accepted and tolerated monotherapy with CBZ, PHT, VPA, and LTG. No fatal adverse events occurred. Unsatisfactory seizure control was a primary reason for withdrawal from the AED monotherapy study.     

Randomized double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers

PURPOSE: This study aimed at investigating the cognitive and mood effects of lamotrigine (LTG) versus valproate (VPA) and placebo (PBO). METHODS: By studying the effects in healthy volunteers, it is possible to separate the genuine effects of LTG from the cognitive improvements, caused by better seizure control. The study used a pretest-posttest comparison of 50 mg LTG, 900 mg VPA, or PBO in a double-blind single-dummy parallel-group design with 30 healthy volunteers. Study duration was 12 days (with a last control on day 13). Outcome measures included cognitive tests (FePsy neuropsychological test battery), mood scales (ASL; mood-rating scale), and a scale for subjective complaints (ABNAS Neurotoxicity scale). Total sleep time was controlled with actigraphic recordings. The results were analyzed by comparing the change over time (pretest with posttest) for the three treatments with Student's t tests. RESULTS: COGNITIVE TESTS: significant differences between the treatments were found for measurements of cognitive activation (i.e., three of the four simple reaction-time measurements showed statistically significant differences in change between PBO and LTG in favor of LTG (p=0.03; 0.03; 0.04); two of four tests showed statistically significant differences in change between LTG and VPA, both in favor of LTG (p=0.03; 0.05). SUBJECTIVE COMPLAINTS: the ABNAS-neurotoxicity scale reveals a significant reduction of drug-related cognitive complaints for the subjects taking LTG, relative to VPA (p=0.02). MOOD RATING: significant changes were found on the scale assessing "tiredness," showing increased tiredness/sedation for VPA relative to PBO (p=0.02) and on the "timid scale" for LTG reporting "being more at ease" compared with both PBO and VPA (p=0.02; 0.02). The general direction of change for the mood scales was toward "activation" for LTG (five of six scales improved), whereas for VPA, the reverse effect was found (four of six scales showed a change in the direction of "tiredness/sedation"). CONCLUSIONS: Short-term treatment in normal volunteers with a low dose of LTG resulted in improved cognitive activation on simple reaction-time measurements, a more positive subjective report about the impact of drug treatment relative to VPA, and mood changes concurring with the activating effect demonstrated by the cognitive tests.     

高效液相色谱法测定血浆中拉莫三嗪浓度

本文报告一种用高效液相色谱快速分析抗癫痫新药拉莫三嗪的方法。３，５－二胺－６－（２甲氧苯）－ｌ，２，４一三嗪作为内标，标本经乙酸乙酯萃取，蒸干后用５０μｌ乙醇重溶，取１０μｌ进样。色谱条件是以Ａｌｔｅｘ正相色谱柱（４．６ｍｍＩＤ×７．５ｃｍ，ｄｐ３μｍ）作为分析柱，乙烷：乙醇：胺水为８０：２０：０．２５作为流动相，检测器波长置３１３ｍｍ处。结果表明本法具有快速、灵敏、选择性高等特点，完全适用于拉莫三嗪的血浓度监测。