加用阿立哌唑对利培酮所致精神分裂症男性患者高催乳素血症的影响

目的 探讨加用阿立哌唑对利培酮所致的首次发病的男性精神分裂症患者高催乳素血症的影响及安全性.方法 将80例男性精神分裂症首次发病住院患者随机分为研究组(40例)和对照组(40例).使用利培酮治疗4周后催乳素水平≥60 μg/L的患者,在维持原有治疗不变的基础上,研究组加用阿立哌唑5 mg/d,对照组加用安慰剂治疗,总疗程12周,研究周期8周(第4～12周末).于治疗第0,4,8,12周末检测血清催乳素含量,并用阳性和阴性症状评定量表(PANSS)、治疗中需要处理的不良反应量表(TESS)进行评定.结果 研究组治疗第12周末血清催乳素[(25±7)μg/L]较第4周末[(76±17)μg/L]下降,差异有统计学意义(t=15.87;P＜0.01).对照组治疗第12周末催乳素[(79±13)μg/L]与第4周末[(78±15)μg/L]比较,差异无统计学意义(t=0.72;P＞0.05);治疗第12周末催乳素下降率为(66 ±11)%、正常率为67.6%,均高于对照组[分别为(-1±18)%、6.5%](P均＜0.01).两组患者治疗前后比较,PANSS评分总分及分量表分均明显下降(P均＜0.01);在治疗第12周未两组之间各项评分比较,筹异均无统计学意义(t=0.40,0.76,0.22,0.88;P均＞0.05).治疗第12周未研究组TESS评分(4.8±4.3)与对照组(4.5±3.9)的差异无统计学意义(t=0.29;P＞0.05).结论阿立哌唑治疗利培酮所致精神分裂症男性患者高催乳素血症有效,安全.     

阿立哌唑对利培酮所致高催乳素血症的疗效

目的:探讨阿立哌唑治疗利培酮所致高催乳素血症的有效性和安全性。方法:对19例利培酮所致高催乳素血症的男性精神分裂症患者,合并阿立哌唑10 mg/d。分别于治疗前、治疗2、4、8周检测血清催乳素水平;在治疗前、治疗8周评定阳性与阴性症状量表(PANSS)、临床总体印象量表-疾病严重度(CGI-S)、Barnes锥体外系不良反应量表(SAS)、Barnes静坐不能量表(BAS)和UKU不良反应量表(UKU)。结果:治疗4周催乳素水平显著下降(P<0.001),而治疗4周与治疗8周催乳素水平差异无显著性(P>0.05);研究结束时,所有患者催乳素水平下降超过50%,其中6例降至正常,5例患者催乳素相关症状均有改善;治疗前后PANSS、CGI-S、BAS和SAS评分差异无显著性(P>0.05)。结论:阿立哌唑可有效治疗利培酮所致的高催乳素血症,不良反应少。     

阿立哌唑治疗利培酮所致精神分裂症女性患者高催乳素血症的研究

目的 探讨阿立哌唑治疗利培酮所致女性患者高催乳素血症的疗效及安全性.方法 117例利培酮所致高催乳素血症的女性患者,随机分为治疗组(60例)和对照组(57例).维持原有利培酮治疗不变,治疗组加用阿立哌唑5 mg,对照组加用安慰剂治疗,疗程均为6周.于治疗第0,6周末检测催乳素,评定简明精神病量表(BPRS)、治疗中需处理的不良反应症状量表(TESS).结果 (1)治疗第6周末,治疗组催乳素[(26±6)μg/L]较基线[(112±40)μg/L]下降,差异有统计学意义(P=0.000);对照组催乳素[(99±44)μg/L]与基线[(104±34)μg/L]比较,差异无统计学意义(P=0.180).(2)治疗第6周末,治疗组催乳素下降率[(75±8)%]、正常率(82%),均高于对照组[分别为(5+30)%,4%];P均=0.000.(3)治疗第6周末,治疗组[(20.4±2.1)分]、对照组[(20.8±1.9)分]BPRS评分均较基线[分别为(21.1±1.8)分,(21.4±1.9)分]下降,P均=0.045;两组不良反应发生率相近(P=0.553).结论 阿立哌唑治疗利培酮所致精神分裂症女性患者的血高催乳症有效、安全.     

桂附地黄丸治疗抗精神病药引起的高催乳素血症

目的：探讨桂附地黄丸治疗精神分裂症患者使用抗精神病药物后出现的高催乳素血症的疗效。方法：对31例（男21例,女10例）血清催乳素水平〉34.12μg/L的精神分裂症患者给予桂附地黄丸18 g/d治疗,抗精神病药剂量不变;8周后测定血清催乳素浓度。用阳性与阴性症状量表（PANSS）、治疗中出现的症状量表（TESS）评定精神症状和药物不良反应。结果：桂附地黄丸治疗8周后血清浓度有显著下降（t=2.323,P=0.021）,平均降低20.1%。结论：桂附地黄丸能有效降低由抗精神病药物引起的血清高催乳素水平,具有较好的安全性和依从性。     

早期催乳素水平预测利培酮有效剂量

目的 :　探索口服利培酮或氯氮平 4天时催乳素 (PRL)的水平与 4周疗效的关系。方法 :　测定服利培酮 1mg/d和服氯氮平 10 0mg/d 4天时的PRL水平 ,以简明精神病量表 (BPRS)评定疗效。结果 :利培酮组 4天的PRL水平显著高于氯氮平组。利培酮组女病人明显高于男病人 ;PRL≥ 6 9.2 μg/L的男病人疗效明显优于PRL <6 9.2 μg/L者。　 结论 :利培酮组PRL≥ 6 9.2 μg/L的男病人可能为药物慢代谢型 ,后来只要服 (3.7± 0 .5 )mg/d的剂量即达到有效浓度 ,而PRL <6 9.2 μg/L者可能为药物快代谢型 ,需服≥ 4mg/d剂量才能达到有效浓度 ,服氯氮平组的PRL水平对预测有效剂量没有价值     

溴隐亭干预女性利培酮致严重高催乳素血症4例

1病例病例1:患者,女性,26岁。诊断:精神分裂症。入院时查血催乳素:30μg/L。给予利培酮治疗,1周后增至6mg/d,2周后精神症状得以控制,服药30d左右时,患者出现抑郁情绪,感觉活着没有意思。查血催乳素235μg/L;简明精神     

低频重复经颅磁刺激对慢性精神分裂症患者血清催乳素水平的影响

目的 探讨低频重复经颅磁刺激(rTMS)治疗抗精神病药所致高催乳素血症的疗效及安全性.方法 将61例利培酮所致高催乳素血症的住院军人慢性精神分裂症患者随机分为两组,在原有利培酮剂量稳定不变的基础上,分别予以10 d的1Hz低频删S刺激(31例)及假rTMS刺激(30例).于刺激前、后对两组分别进行血清催乳素(PRL)测定及阳性和阴性症状量表(PANss)、17项汉密尔顿抑郁量表(HAMD-17)评定,同时观察高催乳素血症临床症状的变化情况,并于1个月后对研究组的血清PRL水平进行复测.结果 (1)研究组rTMS刺激后PRL水平[(27.9±7.1)μg/L]较治疗前[(101.5±41.2)μg/L]下降,差异有统计学意义(P＜0.01);对照组治疗后PRL水平[(111.4±44.5)μg/L]与治疗前[(106.6±41.9)μg/L]比较,差异无统计学意义(P＞0.05);研究组疗效明显优于对照组(F=22.3,P＜0.01);研究组治疗1个月后复测PRL[(96.7±38.3)μg/L],已恢复至治疗前水平(P＞0.05).(2)研究组男性乳房女性化消失(8/14),自发泌乳消失(11/17),月经恢复(4/7),对照组则均无改善.(3)与治疗前比较,治疗后研究组及对照组PANSS及HAMD-17评分变化均无统计学意义(均P＞0.05).两组不良反应均较轻,除头痛研究组多于对照组外,其余不良反应发生率两组相近.结论 短期低频rTMS治疗可使慢性精神分裂症患者服用抗精神病药所致高催乳素血症的症状减轻,且安全性较好,但需进一步的rTMS维持治疗以巩固疗效.     

利培酮对女性精神分裂症患者神经内分泌的影响

目的 探讨利培酮对女性精神分裂症患者神经内分泌的影响。方法 对58例女性精神分裂症患者存利培酮治疗至少6个月后,检测性激素水平及利培酮血药浓度。并与30名健康女性进行对照分析。结果 研究组催乳素(PRL)、睾酮水平均显著高于对照组(P<0.01),而雌二醇、孕酮水平则显著低于对照组(P<0.01)。溢乳组PRL水平显著高于无溢乳组(P<0.01),ROC曲线显示,当PRL≥98.0μg/L时溢乳的危险性升高。结论 ①利培酮治疗后可见血催乳素、睾酮水平升高,雌二醇、孕酮水平降低;②催乳素≥98.0μg/L时发生溢乳的危险性升高。探讨利培酮对神经内分泌的影响还需进一步做前瞻性研究。     

抗精神病药对妊娠和哺乳的影响

精神分裂症和双相障碍妇女都可能服抗精神病药治疗,而抗精神病药对妊娠和哺乳有何影响,一直是精神科医生所关心的问题,本文综述了抗精神病药对妊娠和哺乳的影响。1高催乳素血症1.1机制抗精神病药强效阻断垂体前叶D2受体,迅速增加催乳素分泌,引起高催乳素血症（定义为血浆催乳素浓度〉20μg/L）.1.2机率引起高催乳素血症的率利培酮最高（88%,记作90%）,典型抗精神病药次之（48%,记作50%）,     

奎硫平与氯丙嗪对血清催乳素的影响

目的:探讨奎硫平与氯丙嗪对精神分裂症患者血清催乳素(PRL)的影响及血清PRL水平与药物疗效的相互关系。方法:对191例精神分裂症患者分别以奎硫平或氯丙嗪治疗。以阳性与阴性症状量表(PANSS)进行评估,同时测血清PRL浓度,于治疗前及治疗8周时各测1次。结果:经8周治疗,氯丙嗪组血清PRL(680.23±90.26)μg/L,显著高于奎硫平组(124.24±13.56)μg/L(P<0.001)。奎硫平组男女患者血清PRL水平差异无显著性(P>0.05);氯丙嗪组女性血清PRL(785.72±15.81)μg/L,显著高于男性的(557.75±99.23)μg/L(P<0.05),两组患者血清PRL浓度与PANSS减分率均无显著相关。结论:奎硫平对精神分裂症患者血清PRL水平基本无影响,氯丙嗪可明显升高患者血清PRL水平。血清PRL水平与药物疗效无显著相关。     

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.