氯氮平合并丙戊酸钠治疗难治性精神分裂症疗效及相关因素观察

目的 探讨氯氮平合并丙戊酸钠治疗难治性精神分裂症的疗效及其它相关因素。方法 抽取64例难治性精神分裂症患者给予氯氮平≥400mg/日,合并丙戊酸钠≥800mg/日治疗3个月,用简明精神病量表(BPRS)及药物副反应量表(TESS)评定疗效及副作用,并对其它相关因素进行分析。结果 发现氯氮平合并丙戊酸钠治疗难治性精神分裂症阳性、阴性症状均有效,总有效率为56.25％,尤其对女性及<22岁的患者疗效好,对激活因子及敌对猜疑因子疗效较佳,副作用轻。结论 氯氮平合并丙戊酸钠可作为治疗难治性精神分裂症,尤其是女性及<22岁患者较理想的方法。     

丙戊酸钠辅助治疗难治性精神分裂症的作用

目的：评价氯氮平合并丙戊酸钠治疗难治性精神分裂症的疗效和安全性。方法：62例难治性精神分裂症患者随机分为合用组和单用组，分别给予氯氮平合并丙戊酸钠和氯氮平治疗，疗程12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）评定疗效和不良反应结果：单用组显效率为16．7％，有效率为50．0％；合用组显效率43．3％，有效率73．3％，以合用组疗效显著较好（P〈0．05），两组不良反应差异无显著性（P〉0．05）。结论：氯氮平合用丙戊酸钠治疗难治性精神分裂症疗效优于单用氯氮平，不良反应少。     

丙戊酸钠与氯氮平治疗精神分裂症的对照研究

作者报告了丙戊酸钠与氟氮平及丙戊酸钠合并氯氮平治疗１５０例精神分裂症的对照研究，采用简明精神病量表、临床疗效总评量表和治疗药物副反应量表进行评定。结果表明丙戊酸钠起效时间较慢，对精神分裂症各症状群的治疗效果不如氯氮平。     

氯氮平合并利培酮治疗难治性精神分裂症观察

目的：观察氯氮平合并利培酮治疗难治性精神分裂症的疗效和安全性。方法：对30例难治性精神分裂症患者给予氯氮平合并利培酮治疗，疗效8周，治疗前和治疗后进行阳性与阴性症状量表（PANSS）评定疗效和不良反应量表（TESS）评定副作用。结果：治疗8周后总有效率为66.7％，治疗前后PANSS总分及各分量表分均有显著差异。常见副作用是锥体外系症状（EPS），但程度较轻。结论：两药合并治疗难治性精神分裂症是一种有效的治疗方法，安全性高，耐受性及依从性好。     

丙戊酸钠对精神分裂症幻听症状的辅助疗效

目的：探讨丙戊酸钠对精神分裂症患者的幻听症状有无辅助治疗作用。方法：将病人随机分为两组，一组氯丙嗉合合并丙戊酸钠治疗8周，另一组不合并丙戊酸钠治疗。用简明精神病评定量表（BPRS）、阳性症状评定量表（SAPS）、临床疗效总评量表（CGI）及副反应量表（TFSS）综合评定。结果：氯丙嗪合并丙戊酸钠治疗组疗后BP民分、单项幻觉分，以及SAPS总分、幻觉分、幻听分均低于不合并治疗组，尤以1、2周末明显。结论：丙戊酸钠可加快精神分裂症病人幻听症状的消除，且对幻听伴随的焦虑、激越、怪异行为、敌对猜疑等症状亦有一定的疗效。     

氯氮平合并安度利可治疗难治性精神分裂症36例分析

目的：了解氯氮平合并安度利可治疗难治性精神分裂症的疗效和安全性。方法：36例符合CCMD－2－R精神分裂症诊断标准且临床判断属于难治性病人，予以氯氮平合并安度利可治疗，疗程12周，分别于治疗前及治疗后进行阳性和阴性症状量表（PANSS）和不良反应症状量表（TESS）评定，结果：合并治疗12周后总有效率为67．8％，PANSS阳性，阴性及一般精神病理评分治疗前后均有显著性差异（P＜0．01），副作用主要为肌张力增高，结论：对于氯氮平治疗反应不佳的难治性精神分裂症病人合并安度利可治疗仍可取得较好的临床效果，安全性高，耐受性及依从性良好，可作为临床治疗难治性病人的方法之一。     

丙戊酸钠对精神分裂症攻击行为的辅助治疗作用

目的：观察丙戊酸钠合用利培酮治疗精神分裂症攻击行为的疗效与不良反应。方法：63例伴有攻击行为的精神分裂症住院患者分为丙戊酸钠合用利培酮组（研究组）32例和单用利培酮组（对照组）31例,治疗12周。应用阳性和阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）评定疗效及不良反应。结果：研究组PANSS评分（包括兴奋症状分及攻击因子分）改善明显优于对照组（P〈0.05）。研究组较对照组不良反应少且程度轻（P〈0.05）。结论：丙戊酸钠合并利培酮治疗精神分裂症攻击行为的疗效肯定,安全性与耐受性较好。     

丙戊酸钠对氯氮平血药浓度和疗效的影响

目的:探讨合用丙戊酸钠对氯氮平治疗精神分裂症时的血药浓度和疗效的影响。方法:将80例男性精神分裂症患者随机分为两组,单用组40例患者单服氯氮平,合用组40例患者同时服用氯氮平及丙戊酸钠,分别于治疗前、治疗1周和4周末测定氯氮平的血药浓度,同时评定阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)。结果:合用组治疗1周和4周末有部分患者氯氮平血药浓度升高,部分患者降低,与基线期相比,治疗4周末有显著降低。结论:合用丙戊酸钠后氯氮平血药浓度治疗4周末显著降低;丙戊酸钠可以提高氯氮平对阳性症状的疗效。     

奎硫平合并丙戊酸镁缓释片治疗精神分裂症兴奋激越研究

目的：比较奎硫平合并丙戊酸镁缓释片与氟哌啶醇治疗精神分裂症患者伴有兴奋、激越症状的疗效及不良反应.方法：对精神分裂症住院患者采用随机对照、开放性研究治疗2周.以阳性与阴性症状量表（PANSS）及临床疗效总评量表（CGI）评估疗效,以治疗中出现的症状量表（TESS）评估不良反应.结果：合用组与对照组的总体疗效相当,兴奋、激越症状的控制前者优于后者（P＜0.05）;不良反应方面,氟哌啶醇引起的锥体外系不良反应较奎硫平合并丙戊酸镁缓释片高.结论：奎硫平合并丙戊酸镁缓释片对精神分裂症兴奋、激越症状的疗效优于氟哌啶醇,且不良反应较小.     

氯氮平合并利培酮与氯氮平合并舒必利治疗难治性精神分裂症的对照研究

目的：研究对比氯氮平合并利培酮与氯氮平合并舒必利治疗难治性精神分裂症的疗效和安全性。方法：把住院的60例难治性精神分裂症患者，随机分为A，B两组，A组应用氯 平合并利培酮治疗，B组应用氯氮平合并舒必利治疗，观察8周，分别在治疗前与治疗后用阳性与阴性症状量表（PANSS）和不良反应症状量表（TESS）评定。结果：A组治疗8周后总有效率为70％，B组治疗8周后总有效率为63．3％，两组间疗效无显著差异（P＞0．05），TESS总分两组间有显著差异（P＜0．05），B组副反应大。结论：对难治性精神分裂症病人，氯氮平合并利培酮与氯氮平合并舒必利治疗均取得了较好的效果，A组副反应轻。     

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.     

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.