阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响

目的:探讨阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响.方法:63例抗精神病药所致高催乳素血症的老年精神分裂症患者随机分为研究组(33例)和对照组(30例).两组沿用原有抗精神病药物,研究组加用阿立哌唑5 mg/d持续12周.分别于入组前、入组4、8、12周末检测血清催乳素水平,同时采用简明精神病评定量表(BPRS)和治疗中出现的症状量表(TESS)评定精神病性症状及药物不良反应. 结果:入组4、8、12周末研究组血清催乳素水平较入组前及对照组显著降低(P均＜0.05);对照组入组前后血清催乳素水平差异无统计学意义(P均＞0.05).两组人组前后BPRS、TESS评分差异无统计学意义(P均＞0.05). 结论:阿立哌唑可有效降低抗精神病药物所致老年精神分裂症患者血清催乳素水平增高,且并未增加药物不良反应.     

二、精神分裂症药物治疗对照研究（四）：奎硫平与利培酮治疗精神分裂症对照研究

目的：探讨奎硫平治疗精神分裂症的疗效及安全性.方法：将90例精神分裂症患者随机分两组,分别给予奎硫平与利培酮治疗8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,于治疗前及治疗8周末各测血清催乳素.结果：两组之间疗效及不良反应差异均无显著性,但奎硫平组锥体外系反应（EPS）少,且对血清催乳素水平基本无影响.结论：奎硫平是一种有效且更安全的抗精神病药.     

抗精神病药对血清细胞因子的影响

目的：探讨抗精神病药对精神分裂症患者血清细胞因子的影响。方法：对４６例精神分裂症患者给予抗精神病药治疗６周,在治疗前后检测血清ＩＬ－６和ＴＮＦ－α水平,并采用阳性与阴性症状量表（ＰＡＮＳＳ）、副反应量表（ＴＥＳＳ）评估临床症状变化及药物副反应。结果：抗精神病药治疗后,血清ＩＬ－６水平显著下降,血清ＴＮＦ－α水平变化不显著。治疗前血清ＩＬ－６水平与ＰＡＮＳＳ阳性因子分显血清ＩＬ－６水平显著下降,血清     

阿立哌唑治疗舒必利所致男性高催乳素血症

目的：探讨阿立哌唑治疗舒必利所致男性高催乳素血症的疗效。方法：将60例舒必利所致的高催乳素血症的男性精神分裂症患者随机分为两组,分别用阿立哌唑（30例）及安慰剂（30例）治疗,疗程8周。分别于治疗前、治疗8周检测血清催乳素（PRL）水平,以简明精神病评定量表（BPRS）评定疗效,以治疗中出现的症状量表（TESS）评定不良反应。结果：治疗8周后,阿立哌唑组PRL较治疗前显著下降（t=24.65,P〈0.01）,男性乳房女性化消失率73.3%,自发泌乳消失率85.0%,对照组PRL治疗前后差异性无显著性（t=1.40,P〉0.05）。结论：阿立哌唑可有效治疗舒必利所致的男性高催乳素血症。     

阿立哌唑与利培酮治疗精神分裂症随机双盲对照研究

目的：评价阿立哌唑治疗精神分裂症的有效性和安全性。方法：将52例精神分裂症患者,随机分配到阿立哌唑组26例和利培酮组26例,进行为期6周的随机双盲对照研究。采用阳性和阴性症状量表（PANSS）、临床疗效总评量表（CGI）、治疗中出现的症状量表（TESS）及有关实验室检查评定疗效和安全性。结果：治疗6周两组PANSS评分较治疗前均显著降低（P均〈0．05）,各时点PANSS评分两组间减分差异无统计学意义。治疗6周末,阿立哌唑组有效率58．3％,利培酮有效率75％,两组比较差异无统计学意义（χ^2=1．50,P=0．221）。两组均未发生严重相关不良事件。阿立哌唑组对血清催乳素的影响较利培酮组小。结论：阿立哌唑治疗精神分裂症的疗效与利培酮相当,对催乳素无影响,是一种安全而有效的抗精神病药物。     

抗精神病药合并帕罗西汀治疗慢性精神分裂症

目的：探讨抗精神病药合并帕罗西汀治疗慢性精神分裂症阴性症状的疗效。方法：对68例以阴性症状为主的慢性精神分裂症患者，在原用抗精神病药基础上，随机分为合用组和对照组，分别给予帕罗西汀和安慰剂，疗程12周。疗效和药物不良反应评定采用阳性与阴性症状量表（PANSS）和治疗中出现的症状量表（TESS），于治疗前及治疗4、8、12周各评定一次。结果：治疗第8周起合用组PANSS总分及阴性因子分均比治疗前显著降低。结论：以阴性症状为主的慢性精神分裂症患者，在使用抗精神病药同时联用帕罗西汀可改善阴性症状，两组不良反应无明显差异。     

阿立哌唑与齐拉西酮治疗抗精神病药物所致高催乳素血症精神分裂症的临床对照研究

目的观察阿立哌唑与齐拉西酮治疗抗精神病药物所致高催乳素血症精神分裂症的效果。方法将46例就诊于重庆市精神卫生中心符合《国际疾病分类(第10版)》(ICD-10)诊断标准、单一服用抗精神病药治疗后出现血清催乳素(PRL)水平升高的精神分裂症患者,按照随机数字表法分为阿立哌唑组和齐拉西酮组各23例。入组前两组患者服用药物为利培酮、奥氮平、氨磺必利和舒必利。采用重叠交叉法对两组分别换用阿立哌唑与齐拉西酮治疗,观察8周。于治疗前和治疗4、8周末采用放射免疫法检测血清PRL水平,采用阳性和阴性症状量表(PANSS)和副反应量表(TESS)评定疗效和不良反应。结果治疗8周末,阿立哌唑组与齐拉西酮组血清PRL水平均较治疗前低,差异均有统计学意义(F=266.113、157.376,P均0.01);且同期阿立哌唑组血清PRL水平较齐拉西酮组低,差异有统计学意义(F=11.692,P0.01);两组PANSS总评分治疗前后比较差异均无统计学意义(F=2.166、0.386,P均0.05)。两组均无严重不良反应,不良反应发生率差异无统计学意义(χ~2=4.00,P0.05)。结论阿立哌唑与齐拉西酮均能在控制精神分裂症症状的基础上缓解抗精神病药物所致的高催乳素血症,且阿立哌唑降低血清PRL水平的效果可能优于齐拉西酮,均无严重不良反应。     

抗精神病药对老年精神分裂症患者血清催乳素的影响

目的：探讨几种抗精神病药对老年精神分裂症患者血清催乳素（PRL）的影响。方法：随机选取抗精神病药治疗老年精神分裂症患者121例,分别在治疗前后测定血清PRL水平。结果：患者经舒必利、奋乃静、氟哌啶醇和利培酮治疗后血清PRL明显升高,各药物之间以及治疗前后比较差异均有显著性（F=15．95,P〈0．01）。PRL水平的升高与药物剂量呈正相关。氯氮平对PRL水平影响不明显。结论：典型和非典型抗精神病药对老年精神分裂症患者血清PRL水平的影响同样明显,强弱的顺序依次是舒必利、奋乃静、氟哌啶醇和利培酮。     

脑苷激肽合并抗精神病药物治疗精神分裂症临床疗效观察

目的 观察脑苷激肽合并抗精神病药物治疗精神分裂症的临床疗效观察。方法 将80例精神分裂症患者随机分为两组，分别给予抗精神病药物合并脑苷激肽联合治疗（观察组），和单用抗精神病药物（对照组），治疗为8周。采用简表精神科量表（BPRS），阴性症状量表（SANS）定期进行评定。结果 观察组总有效率为85％，对照组为70％，差异显著（x^2=3.66，P＜0.05），两组（BPRS），（SANS）评分在第2周、第4周、第8周、差异均有显著性（P＜0.01）。结论 用脑苷激肽合并抗精神病药物治疗精神分裂症比单纯应用抗精神病药物疗效显著。     

拉莫三嗪对精神分裂症阴性症状的辅助治疗作用

目的：探讨拉莫三嗪合并抗精神病药，治疗精神分裂症阴性症状的疗效与安全性。方法：对以阴性症状为主的精神分裂症患者50例，按入院顺序随机分为抗精神病药物合并拉莫三嗪组，（合用组）和单用抗精神病药物组（单用组），疗程12用。采用阳性与阴性症状量表（PANSS）评定疗效．用治疗中出现的症状量表（TESS）评定不良反应，于治疗前及治疗4、8、12周各评定一次。结果：合用组显效率64％，单用组硅效率40％。从治疗4周起，合用组PANSS总分及阴性症状分均显著低于单用组。结论：以阴性症状为主的精神分裂症患者．在使用抗精神病药物同时联用拉莫三嗪，可改善阴性症状，两组不良反应无明显差异．     

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.     

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.     

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.     

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.     

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.     

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.