Reduction of epileptiform activity in response to low-dose clonazepam in children with epilepsy: a randomized double-blind study

PURPOSE: To evaluate the effect of low-dose clonazepam (CZP) on the amount of epileptiform activity in children with focal and generalized epilepsy. METHODS: In a single-blind pilot study, followed by a double-blind, placebo-controlled, randomized, crossover study, 15 children with epilepsy were evaluated by using 24-h long-term EEG recordings during baseline days and days after injections of placebo and CZP. The drug was given as a single i.m. injection of 0.02 mg/kg BW. Blood samples were obtained regularly for analysis of plasma concentrations of CZP. The number of epileptiform discharges was determined during corresponding periods with the individual child in the same state of alertness, the same real time of day, and with concomitant antiepileptic drugs (AEDs) unchanged. RESULTS: In the double-blind study, low-dose CZP produced a highly significant (p = 0.0015) decrease in the amount of epileptiform activity (mean, -69% vs. placebo, -2%) obtained during periods when median plasma concentrations ranged from 18 to <14 nM. The maximal plasma level (median, 24 nM) was reached before the start of the analysis periods. The pilot study showed reductions of epileptiform discharges within the same range as the double-blind study. In the children with daily seizures, a parallel decrease in seizures and the number of epileptiform discharges was seen after the administration of CZP. CONCLUSIONS: Our data demonstrate a significant reduction of epileptiform discharges on long-term EEGs after a single low dose of CZP with concomitant low plasma levels, which were considerably lower than the doses and plasma levels usually recommended. A concomitant reduction of seizures also was seen.     

高效液相色谱法同时测定人血浆中地西泮、硝西泮、氯硝西泮

目的:建立同时测定人血浆中地西泮、硝西泮、氯硝西泮浓度的高效液相色谱方法.方法:采用Shim-pack CLC-CN色谱柱,以正己烷-无水乙醇-甲醇(90:9:1)为流动相,柱温为40℃,紫外检测波长为240 nm,血浆样品经乙醚提取后进样.结果:地西泮、硝西泮、氯硝西泮分别在0.1～10.0,0.01～0.50,0.01～0.50 mg·L-1范围内线性关系良好(r≥0.999 6),方法平均回收率分别为99.4%,99.0%,101.1%.日内和日间RSD≤5.3%(n=6).结论:本方法灵敏准确、简便易行,适用于治疗药物监测及中毒药物快速分析测定.     

高效液相色谱法同时测定四种抗癫痫药物的血药浓度

目的：建立用HPLC同时测定血清中多种抗癫痫药物卡马西平( carbamazepine,CBZ)、苯巴比妥( phenobarbital, PB)、硝西泮( nitrazepam,NTZ)、氯硝西泮( clonazepam,CNZ)等的方法。方法用一定方法处理血清样本,色谱柱为Nova-pak C18柱(150 mm ×3.9 mm,4μm);流动相为0.01 mol/L磷酸二氢钾缓冲液(pH 2.15)-乙腈(29∶71,V/V),监测波长223 nm;流速1 ml/min,柱温30℃。结果样品血清经处理,所留杂质不干扰被检测药品。在该色谱条件下以上药物能良好分离,在0.01-10 mg/L范围浓度与峰面积呈良好的线性关系(r>0.9990),方法回收率均大于90%,日内、日间RSD均小于10%。结论该方法快速、准确、简便、实用,适用于以上治疗药物的治疗监测。     

胶束电动毛细管色谱法快速分析人血浆中的抗癫痫药物

目的建立胶束电动毛细管色谱(MECC)法分析人血浆中的多种抗癫痫药物的方法。方法运行缓冲液为50 mmol·L^-1 SDS-8 mmol·L^-1 Na₂HPO₄-3 mmol·L^-1 Na₂B₄O₇ (pH 8.0)-乙腈(18%)。毛细管总长50 cm，有效长度45.5 cm，内径50 μm。操作电压25 kV，运行温度30 ℃。检测波长210 nm。考察了各种因素对MECC分离的影响。结果线性范围：扑米酮1.0～40.0 μg·mL^-1，苯巴比妥1.0～60.0 μg·mL^-1，苯妥英1.0～60.0 μg·mL^-1，卡马西平1.0～40.0 μg·mL^-1，氯硝西泮0.2～8.0 μg·mL^-1，线性良好，相关系数均大于0.999 1；精密度良好，日内、日间RSD均小于15.0%；提取回收率80.0%～100.0%，RSD均小于10.0%。结论胶束电动毛细管色谱法可同时检测人血浆内多种抗癫痫药物的含量，方法成本低、操作简便、快速准确、干扰因素少。     

A Case of Tardive Tourette-Like Syndrome

Abstract: We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromseine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.     

Blood choline and response to clonazepam and haloperidol in Tourette's syndrome

This paper reports the results of a single blind clinical study of drug treatment response of 20 patients with Tourette's syndrome to haloperidol and clonazepam. Because patients with Tourette's syndrome have been reported to have increased red blood cell choline levels, choline levels were examined in relation to treatment response. Differential drug treatment response was found among patients with high versus low red blood cell-to-plasma choline ratios. Patients with high red blood cell-to-plasma choline ratios responded better to clonazepam than to haloperidol. This suggests that there may be two distinct subtypes of patients with Tourette's syndrome.     

Aminoglutethimide but not spironolactone enhances the anticonvulsant effect of some antiepileptics against amygdala-kindled seizures in rats

Summary. Aminoglutethimide (AGLD, an inhibitor of adrenal steroid synthesis) up to 5mg/kg and spironolactone (SPIR, a mineralocorticosteroid antagonist and a weak antiandrogen) up to 50mg/kg did not affect any seizure parameter in amygdala-kindled rats. AGLD (10mg/kg) significantly reduced seizure activity in rats of both gender. The combination of AGLD (5mg/kg) with phenobarbital (PB, applied at its subeffective dose of 15mg/kg) significantly shortened motor seizure and afterdischarge duration in amygdala-kindled seizures. The combined treatment of AGLD (5mg/kg) and clonazepam (CLO) at its subeffective dose of 0.01mg/kg caused significant reduction of the seizure severity, seizure duration and afterdischarge duration. Finally, AGLD (5mg/kg) proved ineffective upon the action of valproate (VPA) in this model of epilepsy. In contrast to AGLD, SPIR (50mg/kg) did not affect the action of PB, CLO or VPA against kindled seizures in rats. AGLD did not alter the free plasma levels and brain concentration of PB or CLO, so a pharmacokinetic interaction does not seem probable. Among a variety of chemoconvulsants, bicuculline and N-methyl-D-aspartic acid reversed the effects of AGLD/PB and AGLD/CLO combinations. Aminophylline, kainic acid, strychnine and the glucocorticosteroid (hydrocortisone) were ineffective in this respect. Our data confirm the hypothesis that AGLD-mediated events may play a role in seizure activity and can affect the anticonvulsant activity of some conventional antiepileptic drugs against kindled seizures. Moreover, extrapolation of obtained results to clinical practice may indicate that patients with complex partial seizures may be safely co-medicated with AGLD or SPIR without the risk of worsening of seizure control.     

Psychopharmacological and electroconvulsive treatment of anxiety and depression in the elderly

The pharmacotherapeutics of antianxiety and antidepressant medication in the elderly is reviewed, and the benefits and risks of electroconvulsive therapy (ECT) are discussed. Physiological changes in normal ageing are described, and the pharmacodynamic and pharmacokinetic implications are addressed. Finally, the role of the advanced practice nurse (mental health/psychiatry) is discussed in terms of accountability, collaboration, and the development of empirical knowledge to enhance quality patient care.     

Systematic Reviews Published in the July 2012 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The July 2012 issue (3rd DVD for 2012) contains 5131 complete reviews, 2235 protocols for reviews in production, and 18,306 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 674,000 randomized controlled trials, and 15,700 cited papers in the Cochrane methodology register. The health technology assessment database contains just over 11,000 citations. Eighty-six new reviews have been published in the last 3 months, of which six have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 5.715. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided.