氯氮平治疗精神分裂症临床疗效与血浓度研究

目的 探讨氯氮平治疗精神分裂症的临床效应与剂量、血药浓度、的关系。方法 用不同剂量氯氮平治疗精神分裂症64例(A组200mg／日，22例，B组400mg／日，24例；C组600mg／日，18例)，用简明精神症状评定量表(BPRS)和临床总体印象量表(CGI)及副反应量表(TESS)评定疗效及副反应，并测定治疗第2、4、8周末晨服药前的稳态血浓度，共观察8周。结果 (1)三组比较总有效率，BPRS总减分率，TESS增分值均有显差异(P＜0．05)；(2)氯氮平血浓度与剂量呈正相关；(3)血浓度与结束时BPRS评分之间呈负相关(P＜0．05)；(4)高剂量组副反应明显大于低剂量组(P＜0．05)；(5)血浓度与TESS评分之间的关系尚不能确定(P＞0．05)。结论 推荐单用氯氮平治疗精神分裂症的稳态血药浓度为400μg／L左右。     

氯丙嗪对氯氮平血浓度的影响

目的：探索氯丙嗪对氯氟平血浓度的影响。方法在12例精神分裂症病人固定氯氮平剂量1周后,查氯氮平血浓度作为基础浓度,然后用1周时间加用氯丙嗪,再固定剂量1周后,查氯氮平血浓度作为处理后浓度。结果处理后浓度（527±300μg／L）比基础浓度（302±125μg／L）显著为高（P＜0．02）。结论氯丙嗪能升高氯氮平血浓度。     

利培酮治疗复发精神分裂症1633例临床观察

目的：了解利培酮治疗复发精神分裂症患者的疗效与安全性。方法;在全国各大区近40家医疗机构收集复发精神分裂症病人1633例,以可变剂量利培酮治疗,以简明精神病评定量表（BPRS）、临床疗效评定、看护者疗效评定等评定疗效,以不良反应症状量表、合并用药情况,实验室监测评价安全性。结果：根据BPRS总分减分率评定疗效达显著好转或基本痊愈者为87．1％;临床评定疗效达痊愈或显好者为78．1％,看护者评定为很有效者为53．0％。结论：对于不同年龄的复发精神分裂症病人,利培酮是一个安全、有效的新型抗精神病药,一般剂量≤4mg/d即有明显疗效,主要不良反应为锥体外系症状,病人的服药依从性良好。     

精神分裂症病人维持治疗中的依从性研究

为了研究门诊精神分裂症病人在维持治疗中的依从性，对３９７例门诊精神分裂症病人在维持治疗中的服药依从性采用直接面询法进行了研究。结果显示，完全依从的有２９９例，占７５．３％，部分依从和不依从的有９８例，占２４．７％。＞３０岁组的依从性较≤３０岁组的好（Ｐ＜０．０１），家庭人际关系好的病人依从性优于家庭人际关系差的病人（Ｐ＜０．０１），目前精神症状严重的病人、维持治疗药物剂量（折合氯丙嗪剂量）＞３００ｍｇ／ｄ的病人、ＭｏｒｎｉｎｇＳｉｄｅ康复状态量表评分高的病人依从性差。经逐步多元回归分析，影响服药依从性的主要因素为：家庭人际关系、维持治疗药物剂量、维持治疗时间、慢性精神病病人标准化精神症状量表评分。认为提高病人的依从性能减少疾病的复发。     

94例氯氮平换用维思通治疗精神分裂症临床研究

为探讨氯氮平换用维思通治疗精神分裂症的可行性、有效性及安全性，找出能在临床中推广的规律，选择符合CCMD－Ⅱ－R精神分裂症诊断标准、既往采用氯氮平治疗的患共94例，系统换用维思通治疗16周进行观察。在治疗中及治疗前后以BPRS和TESS量表评定疗效和副作用。结果，有效率86％、显效率66％、恶化4％，BPRS总分及因子分治疗前后均有极显性差异（P＜0．001）。常见的副作用为EPS（23％）及失眠（15％），以安坦及苯二氮Zhuo类药处理有效，其它副作用不多见，副作用与维思通剂量有关。提示，氯氮平换用维思通治疗精神分裂症可行、有效且较安全。     

工娱疗法合并氯氮平治疗慢性精神分裂症的对照研究

目的探讨工娱疗法合并氯氮平治疗慢性精神分裂症的效果。方法将112例服用氯氮平治疗的慢性精神分裂症患者随机分为工娱治疗组和对照组。工娱治疗组进行为期16周的训练。采用简明精神症状量表（BPRS）、阴性症状量表（SANS）、临床疗效总评量表（CGI）进行临床效果评定，日常生活能力量表（ADL）来评定患者的日常生活能力。用药物依从性量表来判断患者的服药情况。结果治疗16周末，治疗组患者的服药依从性。慢性精神分裂症阴性症状的缓解，患者的日常生活能力的提高都优于对照组P〈0．05）。结论工娱疗法有助于慢性精神分裂症的治疗和康复。     

阿立哌唑与氯氮平维持性治疗精神分裂症的疗效比较

目的了解阿立哌唑对精神分裂症病人维持治疗的疗效、安全性及社会功能。方法77例精神分裂症出院病人，分为阿立哌唑组（20mg／d）和氯氮平组（300mg／d），采用简明精神病评定量表评定疗效，以不良反应量表评定不良反应，以社会缺陷量表评定社会功能。结果一年内阿立哌唑组病情恶化率22．9％，氯氮平组恶化率16．7％，组问有显著差异。阿立哌唑组要求换药率8．8％，氯氮平组要求换药率42．3％，组问无显著性差异（P〈0101）。观察结束时，阿立哌唑组社会功能缺陷总分（1．50±0．13），氯氮平组（4．39±0.78），组间有显著性差异（P〈0．01）。不良反应评定，氯氮平组高于阿立哌唑组（P〈0．01）。结论精神分裂症病人的维持治疗，阿立哌唑优于氯氮平。     

哌泊噻嗪合并治疗难治性精神分裂症的研究

目的：了解哌泊噻嗪与氯氮平治疗慢性难治性精神分裂症的疗效、副反应和血药浓度。方法：对84例慢性难治性精神分裂症患者随机分为联合组和单用组，在治疗前、治疗后1、2、3、6月进行简明精神病评定量表（BPRS）和不良反应症状量表（TESS）评定，并监测氯氮平血浓度。结果：总疗效联合组明显高于单用组。BRPS总分和各因子分（除焦虑抑郁分外）在治疗后2月即已有明显下降，两组副反应均较轻，氯氮平显效血浓度均高于350μg/L。结论：氯氮平合并哌泊噻嗪治疗慢性难治性精神分裂症具有较好疗效，副作用轻而少。哌泊噻嗪对氯氮平血浓度影响不明显。     

氯氮平血药浓度与临床效应关系探讨

对50例经氯氮平治疗的精神分裂症患者作血药浓度测定,并以BPRS、CGI、TESS量表评定作临床效应分析。结果表明:氯氮平口服剂量与血浓度间里正相关;治疗结束时,血药浓度与BPRS评分间里负相关;治疗有效血浓度阈值为400ng/ml(敏感度75％;特异度80％);血浓度与TESS评分间关系不明显;脑电图异常率与口服剂量、血浓度间呈正相关,且与后者的关系更明显;氯氮平所致白细胞计数异常现象与血药浓度高低无关。     

低剂量氯氮平维持治疗稳定期精神分裂症5年的随访对照研究

目的探讨伊剖量氯氮平对稳定期精神分裂症维持治疗的临床疗效及安全性。方法对1141例稳定期精神分裂症患者随访5年（氯氮平组351例,剂量上限为250mg／d,对照组分别为氯丙嗪组260例、奥氮平组170例和利培酮组360例）：用阳性与阴性综合征量表（PANSS）、临床疗效总评量表病情严重程度项目（CCI—SI）、WHO／残疾评价量表一简化版（DAS—S）、副反应量表（TESS）、心电图、生化检验等评估疗效和不良反应。维持治疗期间要求单一用药,如出现脱落、换药、合并其他抗精神病药物者,作为中断治疗。随访时间5年。结果依据CGI—SI评分,氯氮平组症状恶化例次最低（7．4％）,低于氯丙嗪组（16．9％）、奥氮平组（8．8％）以及利培酮组（14．2％）。研究终点中断率由高到低的单药治疗依次为：奥氮平、氯丙嗪、利培酮、氯氮平。根据Cox模型回归分析的回归系数和相对危险度的估计值判断,影响氯氮平维持时间由短到长的因素依次为：PANSS中的兴奋、概念紊乱,TESS中的困倦、流涎以及心电图异常。结论低剂量氯氮平对稳定期精神分裂症长期维持治疗具有良好的疗效。     

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.     

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.     

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.