帕利哌酮与氟哌啶醇治疗精神分裂症的双盲对照研究

目的 比较帕利哌酮与氟哌啶醇治疗精神分裂症的疗效和安全性.方法 将60例精神分裂症患者随机分为帕利哌酮组和氟哌啶醇组各30例,按双盲法,分别予帕利哌酮和氟哌啶醇单一口服治疗,观察8周.治疗前及治疗后第1、2、4、6、8周末使用简明精神病评定量表(BPRS)、锥体外系副反应量表(SAS)、静坐不能评定量表(BARS)及治疗中需处理的不良反应症状量表(TESS)评定,并测生命体征,基线和治疗结束时进行实验室检查,包括血常规、尿常规、血生化、心电图.观察疗效及不良反应.结果 帕利哌酮组与氟哌啶醇组患者的精神症状均明显改善(F =201.49,P＜0.001),两组之间有效率比较无显著性差异(x2=0.1617,P=1.00).帕利哌酮组静坐不能(Z =2.52,P=0.013)及锥体外系副反应(Z=2.02,P=0.044)均明显少于氟哌啶醇组.实验室检查显示除催乳素水平升幅帕利哌酮组较氟哌啶醇组高(x2=5.08,P=0.04)外,其余均无明显差异.结论 帕利哌酮与氟哌啶醇治疗精神分裂症疗效相当,副反应轻.     

帕利哌酮缓释片与利培酮治疗精神分裂症的对照研究

目的讨论帕利哌酮缓释片对精神分裂症的治疗效果及对患者社会功能的影响。方法采用随机数字表将84例精神分裂症患者分为帕利哌酮缓释剂组和利培酮组,各42例,分别使用帕利哌酮缓释剂和利培酮片治疗,疗程均为8周。两组均在治疗前及治疗第2、4、8周末采用阳性与阴性症状量表(PANSS)评定疗效,副反应量表(TESS)评定不良反应,在治疗前和8周末采用个人和社会功能量表(PSP)评定社会功能恢复状况。结果PANSS评定:两组在治疗前后差异均有统计学意义(P均0.05),同时两组在8周末差异有统计学意义(P0.05)。TESS评定:两组药物的副反应差异无统计学意义(P0.05)。PSP量表评定:两组治疗前后及两组之间相比差异有统计学意义(P0.05),并且帕利哌酮缓释片优于利培酮。结论帕利哌酮缓释片和利培酮治疗精神分裂症阳性及阴性症状均有效。但帕利哌酮缓释片起效相对迅速,不良反应少且轻微,对于精神分裂症患者的整体社会功能改善具有明显的效果。     

棕榈酸帕利哌酮对精神分裂症患者生活质量的影响

目的探讨棕榈酸帕利哌酮对精神分裂症患者生活质量的影响。方法将98例患者分成研究组(棕榈酸帕利哌酮)和对照组(奥氮平),研究组口服三天帕利哌酮,无过敏即予棕榈酸帕利哌酮注射;首次150mg,间隔8天100mg,之后每月一次,剂量75~150mg;对照组口服奥氮平,剂量5mg~30mg,分别在治疗前与治疗后4、8、12、16周末采用阳性与阴性症状评定量(PANSS)、临床总体印象量表(CGI)评定精神症状与疗效的变化;生活质量和满意度自评问卷(Q-LES-Q)评定生活质量和满意度;副作用量表(TESS)、实验室、血生化、体质量评价安全性。结果两组各时点PANSS、CGI、Q-LES-Q评分与治疗前比较均有显著性差异(P0.05或P0.01),PANSS、CGI组间比较差异无显著性(P0.05);Q-LES-Q治疗后组间比较差异有显著性(P0.05或P0.01),实验室、血生化无差异,体重、催乳素组间比较有差异。结论棕榈酸帕利哌酮对精神分裂症疗效、副反应与奥氮平相当;对体重及催乳素影响较奥氮平轻,对生活质量和满意度优于奥氮平。     

帕利哌酮缓释片治疗复发精神分裂症疗效与社会功能评定

目的 探讨帕利哌酮缓释片对复发精神分裂症疗效及社会功能的影响。方法 选取38例复发精神分裂症患者使用帕利哌酮缓释片持续治疗4周,于治疗前及治疗后第4周末采用阳性和阴性综合征量表（PANSS）、个人和社会功能量表（PSP）及治疗中需处理的不良反应症状量表（TESS）评定并比较患者的精神症状、社会功能和不良反应。结果患者治疗后第4周末PANSS各因子分、总分及PSP各因子分较治疗前均降低（P〈0.01）;PSP总分较治疗前升高（P〈0.01）。总不良反应发生率42%。结论 帕利哌酮缓释片可有效改善复发精神分裂症患者的精神症状、个人及社会功能,且不良反应轻。     

随机对照研究比较喹硫平与氟哌啶醇治疗精神分裂症的疗效

目的研究喹硫平对精神分裂症患者认知功能及生活质量的改善作用。方法将62名住院或门诊的急性期精神分裂症患者随机分为两组,分别给予喹硫平（n=32）和氟哌啶醇（n=30）治疗,随访16周。分别在基线、第8周、第12周和第16周用阳性与阴性综合征量表（PANSS）、生活质量和满意度自评问卷（Q-LES-Q）、持续性操作测验（CPT）、威斯康星卡片分类测验（WCST）以及成人韦氏智力量表（WAIS）中的数字广度项目盲法评定精神症状、生活质量和满意度以及认知功能。采用重复测量的方差分析比较两组结果。结果喹硫平组有17例完成16周的随访,氟哌啶醇组为14例。喹硫平组与氟哌啶醇组各时点PANSS评分均比基线改善,组间无明显差异。喹硫平组的4个时点平均（标准差）Q-LES-Q得分改善[分别为：49.0（8.1）分,51.2（7.0）分,54.3（10.6）分,54.1（10.3）分,F=11.70,P〈0.001],而氟哌啶醇组无明显改善[分别为：49.5（7.8）分,51.3（8.0）分,50.0（8.7）分,50.5（8.9）分;F=0.33,P=0.701]。在第16周时喹硫平组Q-LES-Q得分高于氟哌啶醇组（t=2.27,P=0.026）。第8周至第16周,喹硫平组WCST完成分类数、CPT的反应时间、WAIS数字广度评分与基线比均明显改善,而氟哌啶醇组的不同时点间评分无明显差异。结论虽然根据PANSS结果,急性精神分裂症患者用喹硫平和氟哌啶醇治疗的疗效相当,但是持续用喹硫平治疗16周者比持续用氟哌啶醇治疗者的生活质量更好,认知缺陷更少。     

重复经颅磁刺激联合帕利哌酮缓释片治疗精神分裂症的对照试验

目的比较重复经颅磁刺激联合帕利哌酮缓释片与单用帕利哌酮缓释片治疗精神分裂症患者的疗效、安全性和社会功能恢复,为临床选择治疗方案提供参考依据。方法选择符合条件的88例精神分裂症患者,随机分成研究组和对照组,治疗时间为4周。在治疗前和治疗后第1周、第2周、第4周末,用阳性与阴性症状量表(PANSS)及减分率评定疗效,治疗时出现的症状量表(TESS)评定不良反应,个体和社会功能量表(PSP)评定患者的社会功能。结果治疗后,与各组治疗前比较,两组PANSS总分及阴性症状分和阳性症状分、PSP均有明显改善,具有统计学意义(P0.05);组间比较,第2周和第4周末PANSS总分和阴性症状分、PSP评分比较差异有统计学意义(P0.05)。至治疗终点,观察组治疗有效率优于对照组(P0.05),两组间TESS评分差异无统计学意义(P0.05)。重复经颅磁刺激和帕利哌酮缓释片都是安全有效、可以耐受的。结论与单一使用帕利哌酮缓释片相比,重复经颅磁刺激联合帕利哌酮缓释片治疗能取得更好的疗效,改善阴性症状和提高社会功能,;同时副反应方面无明显差异。     

帕利哌酮缓释片与齐拉西酮治疗精神分裂症对照研究

目的：比较帕利哌酮缓释片与齐拉西酮治疗精神分裂症的疗效与安全性。方法：99例精神分裂症患者随机分为帕利哌酮组48例和齐拉西酮组51例,分别给予帕利哌酮缓释片和齐拉西酮治疗6周。采用阳性与阴性症状量表（PANSS）、个人与社会功能量表（PSP）和治疗中出现的症状量表（TESS）作为评价指标。结果：治疗2周及6周后,两组PANSS评分均低于治疗前（P均〈0．05）;组间比较,以帕利哌酮组PANSS评分显著低于对照组（P均〈0．05）。与治疗前比较,帕利哌酮组个人与社会功能改善显著[PSP评分治疗前和治疗后分别平均（49．85±7．64）分和（60．32±8．24）分];而齐拉西酮组改善不明显[PSP评分分别平均（48．92±5．40）分和（（53．38±6．90）分],组间比较,差异有显著性（P〈0．001）。帕利哌酮缓释片的主要不良反应为锥体外系不良反应、失眠、便秘、泌乳素升高,齐拉西酮主要为心电图QTc间期延长、失眠、头痛、恶心等。结论：帕利哌酮缓释片治疗精神分裂症的疗效和改善社会功能方面均优于齐拉西酮。     

阿立哌唑联合认知干预对精神分裂症患者认知功能的影响

目的探讨阿立哌唑联合认知干预对精神分裂症患者认知功能的影响。方法将92例精神分裂症患者随机分为阿立哌唑联合认知干预组(研究组,n=46)和阿立哌唑组(对照组,n=46),疗程12周,采用PANSS评估患者的精神症状,WCST、CPT、TMT、CF、HVLT-R及WMS-Ⅲ评估患者的认知功能,TESS评估患者的不良反应。结果治疗12周末两组PANSS各项评分较治疗前均显著降低(P0.01),而研究组阴性症状分、一般症状分及总分较对照组显著降低(P0.05或0.01),阳性症状分较对照组则无明显变化(P0.05)。两组WCST、CPT、TMT、CF、HVLT-R及WMS-Ⅲ评分较治疗前均明显改善(P0.01),且研究组较对照组改善更加明显(P0.05或0.01)。两组患者TESS量表总分差异无统计学意义(P0.05)。结论阿立哌唑联合认知干预对改善精神分裂症患者的认知功能可能优于单用阿立哌唑治疗。     

棕榈酸帕利哌酮注射液与阿立哌唑治疗精神分裂症急性期患者的对照研究

目的:比较棕榈酸帕利哌酮注射液及阿立哌唑治疗精神分裂症急性期患者的疗效及安全性。方法:84例精神分裂症急性期患者随机分为研究组和对照组各42例。研究组给予棕榈酸帕利哌酮注射液75~150 mg/次,分别于第1天、第8天、第(30±3)天肌内注射;对照组给予口服阿立哌唑10~30 mg/d。观察8周。于治疗前后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:两组PANSS总分及各项评分在治疗后各周均较治疗前明显下降(t=2.17~6.16,P0.05或P0.01);两组间比较,研究组PANSS评分较对照组降分明显(t=2.03~4.14,P0.05或P0.01)。两组不良反应发生率差异无统计学意义(χ2=0.48,P0.05)。结论:棕榈酸帕利哌酮注射液和阿立哌唑对精神分裂症急性期患者均有效、安全,但前者起效更快。     

帕利哌酮缓释片与利培酮改善老年精神分裂症患者社会功能的对照研究

目的:探讨帕利哌酮缓释片对老年期精神分裂症患者社会功能的改善。方法:107例老年期精神分裂症患者被随机分为帕利哌酮组54例和利培酮组53例,分别于基线及180 d时采用个人和社会功能量表(PSP)从社会中有用的活动、个人和社会的关系、自我照料、干扰和攻击行为4个维度进行社会功能评估;随访结束时进行药物满意度问卷(MSQ量表)调查。结果:两组在治疗终点时PSP评分与基线相比均有显著提高(P0.01),帕利哌酮组比利培酮组社会功能改善更明显,差异具有统计学意义(P0.01)。治疗后,帕利哌酮组药物满意率为70.4%,明显高于利培酮组(39.6%)(χ~2=10.22,P=0.001)。结论:帕利哌酮缓释片能够明显改善老年精神分裂症患者的社会功能,提高患者的生活质量和药物治疗满意度。     

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.