合并用药对9-羟利培酮血清浓度的影响

目的:研究合并使用常见药物对利培酮活性代谢产物9-羟利培酮稳态血药浓度的影响。方法:182例服用利培酮治疗精神分裂症或分裂样精神病患者,单用或合并其他药物,根据用药情况分为6组,在固定相关药物及剂量一周后采用高效液相色谱(HPLC)紫外线吸收法测定各组血清9-羟利培酮浓度,并分析各组年龄和性别差异。结果:与单用利培酮组相比,合并苯海索或三唑仑组其9-羟利培酮血药浓度显著较高,而合并氯硝西泮或艾司唑仑或普萘洛尔等组差异无统计学意义。结论:合并苯海索时9-羟利培酮血药浓度增高可能与患者对利培酮代谢能力存在个体差异有关。     

利培酮的血药浓度与临床效应的关系

目的 观察利培酮治疗精神分裂症时的血药浓度及其与疗效及不良反应之间的关系。方法 共纳入31例精神分裂症患者,其中男性17列,女性14列,平均年龄31.00±8.98岁。在治疗前及治疗后1周,2周、4周.6周及8周评定PANSS、CGI、TESS及ESRS。采用HPLC方法测定治疗后4周及8周时利培酮及其代谢产物9—羟利培酮的血药浓度。结果 利培酮治疗精神分裂症疗效肯定,不良反应较少,部分患者出现轻度的EPS。服用固定剂量利培酮(4mg/d)治疗8周时利培酮的血药浓度为41.46±17.36nmol/L,9-羟利培酮的浓度为60.88±42.73nmol/L。利培酮及代谢产物的总浓度与疗效有关,利培酮浓度与EPS有关。结论 利培酮是一种有效的抗精神病药,服用治疗剂量时,利培酮及其代谢产物的总浓度与疗效有关,而利培酮的血药浓度与EPS有关,故检测利培酮及其代谢产物9-羟利培酮的药物浓度对指导临床用药具有重要意义。     

中、小剂量利培酮治疗首发精神分裂症患者的血药浓度与疗效关系的对照研究

目的探讨中、小剂量利培酮治疗精神分裂症患者的血药浓度、临床疗效及不良反应。方法将82例精神分裂症患者随机分为口服利培酮剂量2mg／d组和4nq·g／d组。采用RP—HPLC和LC—MS方法测定利培酮（RSP）和9-羟利培酮（9-OH—RSP）之和的血浆浓度。用阳性和阴性症状量表（PANSS）评定临床疗效,用不艮反应症状量表（TESS）评定不良反应。结果4mg／d组（RSP4-9-OH—RSP）血浓度均显著高于2mg／d组。2rag,／d组第l周末PANSS平均减分率〈20％,其它各周末PANSS平均减分率〉20％,而4mg／d组各周末PANSS平均减分率〉20％．2mg／d组TESS评分明显低于4mg／d组。结论（RSP＋9-OH—RSP）血浓度能较好地反映其临床效应。2mg／d和4mg／d利培酮治疗精神分裂症患者疗效相当,4mg／d利培酮治疗时起效更快,但易发生不良反应。     

奥氮平与利培酮治疗女性精神分裂症对照研究

目的:比较奥氮平与利培酮治疗女性精神分裂症的疗效及不良反应. 方法:将60例女性精神分裂症患者随机平分为两组.以奥氮平和利培酮治疗,疗程8周.采用阳性与阴性症状量表(PANSS)及治疗中出现的症状量表(TESS)评定疗效及不良反应. 结果:奥氮平和利培酮治疗女性精神分裂症患者疗效相当,2药均无严重不良反应.但奥氮平的锥体外系反应(EPS)、泌乳及月经紊乱发生率低于利培酮. 结论:奥氮平与利培酮治疗女性精神分裂症患者均有效,前者不良反应更少、更安全.     

利培酮、氯氮平与氯丙嗪的疗效和不良反应及相关因素的研究

目的　比较利培酮、氯氮平与氯丙嗪的疗效和不良反应 ,探讨有关的实验室检查和药物浓度相互关系。方法　将符合CCMD 2 R诊断标准的精神分裂症患者 ,根据临床情况和入院顺序 ,分别进入利培酮组、氯氮平组与氯丙嗪组 ,观察 8周。以PANSS、CGI、TESS和ESRS量表评定药物的疗效和不良反应。同时测定血清泌乳素和药物浓度。结果　治疗 8周后 :①利培酮组、氯氮平线和氯丙嗪组的PANSS量表总分、阴性分量表、一般精神病理学分量表和CGI量表病情严重程度评分均下降 ,而利培酮组和氯氮平组减分较氯丙嗪组明显 (分别P <0 0 1,P <0 0 5 ) ,TESS及ESRS量表的评分也与氯丙嗪组有显著性差异 (分别为P <0 0 1,P <0 0 5 )。②利培酮组、氯氮平组与氯丙嗪组肝功能、心电图检查组间差异有非常显著意义 (均P <0 0 1)。③氯氮平的剂量与去甲氯氮平、氯氮平浓度呈显著相关 ,9 羟利培酮浓度与PRL、利培酮有效率呈显著性相关 ,氯丙嗪浓度与PRL呈显著性相关 (rs=0 .2 6 1,P =0 .0 15 )。结论　利培酮、氯氮平具有较强抗精神病作用 ,相对氯丙嗪更为有效和全面。利培酮的安全性相对较好。     

齐拉西酮与利培酮治疗精神分裂症对照分析

目的比较齐拉西酮与利培酮治疗精神分裂症的疗效和不良反应。方法将符合入组条件的76例精神分裂症患者随机分成2组,分别给予齐拉西酮和利培酮治疗,观察8周,用阳性和阴性症状量表(PANSS)和副反应量表(TESS)及有关实验室检查评定疗效和不良反应。结果治疗后2组PANSS总分及各因子分较治疗前均明显下降(P<0.05),2组间同期比较无差别(P>0.05),齐拉西酮组有效率78.95%,与利培酮组(81.58%)比较无差别(P>0.05)。利培酮组不良反应大于齐拉西酮组,在体质量增加、锥体外系反应和泌乳闭经方面差异显著(P<0.05)。结论齐拉西酮治疗精神分裂症疗效与利培酮相当,不良反应更小。     

利福平对氯氮平与利培酮血药浓度及疗效影响的对照研究

目的对照比较利福平对氯氮平(CLOZ)与利增酮(RIS)血药浓度及疗效的影响。方法氯氮平组(CLOZ组)25例和利培酮组(RIS组)15例均为单用CLOZ和RIS治疗的精神分裂症伴肺结核患者,在持续原来CLOZ和RIS剂量治疗两周以上的基础上分别合用利福平(0.45g/日),共治疗6周。分别于研究前与研究后第2、6周末采用高效液相色谱法(HPLC)测定CLOZ和RIS药物血浓度,同期以阳性和阴性症状量表(PANSS)评定精神症状。结果与利福平合用前比较,合用后第2、6周末的氯氮平和利培酮血深度以及去甲基氯氮平和9-羟利培酮血浓度均有显著下降,期间差异经单因素方差分析检验均存在非常显著性意义;CLOZ组患者合用前和第2、6周末的PANSS阳性症状、一般精神病理因子分以及PANSS总分间差异均有非常显著性意义;CLOZ组患者精神症状恶化者为(16人)明显多于RIS组的(4人),差异有显著性意义(χ2=5.23,P<0.05);CLOZ组患者出现精神症状恶化时间为(13.33±5.55)天,明显短于RIS组的(20.25±7.13)天,差异也有显著性意义(t=2.12,P<0.05)。结论精神分裂症伴肺结核患者的药物治疗应该注意药物的相互作用,利培酮比氯氮平更适用于这类患者的治疗。     

齐拉西酮与利培酮治疗精神分裂症对照研究

目的:评价齐拉西酮治疗精神分裂症的疗效. 方法:60例精神分裂症患者,随机分为齐拉西酮组和利培酮组,每组30例.分别给予齐拉西酮和利培酮治疗,疗程均8周.采用阳性与阴性症状量表(PANSS)评定疗效;以治疗中出现的症状量表(TESS)和锥体外系反应量表(RSESE)评定不良反应. 结果:治疗后两组PANSS总分及各因子分均较治疗前显著下降(P<0.05或P<0.01).齐拉西酮组锥体外系反应(EPS)发生率26.3%明显低于利培酮组53.3%(χ2=4.44,P<0.05). 结论:齐拉西酮与利培酮治疗精神分裂症疗效相当,齐拉西酮为安全有效的抗精神病药.     

奥氮平与利培酮治疗脑器质性精神障碍的对照分析

目的 比较奥氮平与利培酮治疗脑器质性精神障碍的临床疗效和安全性.方法 将60例脑器质性精神障碍患者随机分成奥氮平组和利培酮组,疗程均为4周.采用阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)评定疗效及不良反应.结果 奥氮平与利培酮的疗效差异无显著性.奥氮平的主要不良反应是嗜睡、体重增加,利培酮的主要不良反应是锥体外系反应、失眠.结论 奥氮平与利培酮均是治疗脑器质性精神障碍安全有效的非典型抗精神病药物,可根据患者不同的个体需要分别选择.     

利培酮口服液治疗老年期精神分裂症临床观察

目的:研究利培酮口服液治疗老年期精神分裂症的疗效和不良反应.方法:将51例老年期精神分裂症住院患者随机分为两组,分别给予利培酮口服液和氟哌啶醇治疗6周.以阳性与阴性症状量表(PANSS)评定疗效,用副反应量表(TESS)评定不良反应.结果:利培酮口服液与氟哌啶醇的疗效无显著差异.利培酮口服液的不良反应主要为失眠、恶心等,程度轻微,氟哌啶醇的锥体外系反应较严重.结论:利培酮口服液对老年期精神分裂症有效,不良反应轻微.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.