氯氮平不同剂量对脑电图及脑电池地形图影响的探讨

目的 探讨氯氮平不同剂量与脑电图及脑电地形图变化的关系。方法 将我院１９９６￣１９９７年期间符合ＣＣＭＤ－２－Ｒ精神分裂症诊断，单艇氯氮平治疗的病人１１５例，按不同剂量分组，进行脑电图（ＥＥＧ）及脑电地形图（ＢＥＡＭ）检查，对不同治疗剂量引起脑电活动变化之间关系进行分析。结果 高剂量组较不剂量组、中剂量组较低剂量组致ＥＥＧ及ＢＥＡＭ的异常率高，异常程度重，低剂量组与高剂量组之间异常有显著差异（Ｐ〈     

氯氮平所致脑电图改变与疗效的关系

目的 观察氯氮平所致ＥＧ、ＢＥＡＭ改变与疗效的关系。方法 符合中国精神疾病分类方案与诊断标准（ＣＣＭＤ－２－Ｒ）２５例单用氯氮平治疗的患者，在入组前、给药后３小时、２周、６周检测ＥＥＧ及ＢＥＡＭ，用ＢＰＲＳ观察其疗效。结果，服用氯氮平６周后，８２％患者有ＥＥＧ改变，９２％患者有ＢＥＡＭ改变，给药后３小时的ＥＥＧ２改变与儿有显著差异。氯氮平在有效剂量范围内，血药浓度与疗效无关。结论 服氯氮平后３小时     

奥氮平对脑电图的影响

目的：研究奥氮平引起脑电图改变的特征,及与用药时间,疗效之间的关系。并与氯氮平引起的脑电图异常作比较。方法：符合CCMD－2－R诊断的精神分裂症、分裂样精神病患者,在服药前、服药后1周、2周、4周检测脑电图,用简明精神病评定量表（BPRS）观察其疗效。结果：服用奥氮平后脑电图波率变慢,服用1周后脑电图异常,但与疗效无关,异常率及异常程度均显著低于氯氮平,结论：奥氮平可引起脑电图改变,但程度较轻。     

氯氮平脑电改变预测精神分裂症的疗效

利用氯氮平引脑电明显改变预测精神分裂症临床疗效。方法采用病人自身对照方法，将３９例病人服药两周时是否引起脑电明显改变，分为脑电改变组与脑电无改变组，比较两组临床疗效。结果，氯氮平服药后Ａ组ＥＥＧ主要表现为额，中央，顶部慢波的明显增多，有的病人甚至枕部也出现多慢波；脑电地形图δ、θ频段功率明显增强。Ｂ组脑电图，脑电地形无明显变化。两组疗效比较，经统计学处理有非常显著性差异；脑电改变组与脑电无改变组两     

心电图和脑电图监护下优势侧电休克治疗精神分裂症的研究

目的 比较优势侧有抽搐电休克（ＥＣＴ）与无抽搐ＥＣＴ治疗精神分裂症的疗效、副作用及心电图（ＥＣＧ）、脑电图（ＥＥＧ）的改变。方法 在ＥＣＧ、ＥＥＧ监护下ＥＣＴ治疗精神分裂的症６０例（有抽搐ＥＣＴ３０例,无抽搐ＥＣＴ３０例）并完成简明精神症状量表（ＢＰＲＳ）、大体评定量表（ＧＡＳ）、副反应量表（ＴＥＳＳ）、韦氏记忆测验（ＷＭＳ）评定。结果 有抽搐ＥＣＴ组和无抽搐ＥＣＴ组的疗效均随治疗你们次数的增加而     

奎硫平对精神分裂症患者脑电活动的影响

目的：探讨奎硫平对精神分裂症患者脑电图（EEG）和脑电地形图（BEAM）的影响。方法：对32例服用奎硫平和40例服用氯氮平患者作EEG和BEAM检查,并进行对照研究。结果：奎硫平组和氯氮平组都有EEG和BEAM若干改变,但氯氮平组明显高于奎硫平组。结论：奎硫平引起EEG和BEAM改变例数较少,明显低于氯氮平,以轻度改变为主。     

发作期及发作间期痫性放电对癫痫的诊断价值

目的：探讨发作期及发作间期脑电图对癫痫诊断的意义。方法：对５６例癫痫患者常规脑电图（ＲＥＥＧ）与２４ｈ脑电图（ＡＥＥＧ）进行比较研究。结果（１）ＲＥＥＧ阳性率为３０％，而ＡＥＥＧ的阳性率为８６％；（２）不同类型癫痫在发作期和发作间期大脑活动的规律和特点，ＲＥＥＧ无１例记录到癫痫发作，而ＡＥＥＧ有２７例（４８％）记录到癫痫发作安全过程的大脑电活动变化，结论发作期的ＥＥＧ对确定癫痫类型有重要意义，全身     

定量药物脑电图预测氯氮平对精神分裂症的疗效

为了探讨氯氮平对精神分裂症病人脑电活动的影响，预测该药的近期临床疗效，应用定量药物脑电图（ＱＰＥＥＧ）方法对６３例精神分裂症病人进行了自身前后的对照研究。结果显示，口服一次量２５ｍｇ氯氮平后，精神分裂症Ⅰ型病人Ｏ１导联α２频段能量在服药后第５小时较服药前显著降低（Ｐ＜０．０５），Ｆ４导联δ频段能量在第５小时较服药前显著增高（Ｐ＜０．０５），Ｆ３导联β频段能量有增高趋势，但未达到显著水平。精神分裂症Ⅱ型病人Ｏ２导联α２频段能量在第４小时较服药前显著降低（Ｐ＜０．０５），Ｆ４导联δ频段及Ｆ３导联β频段能量有增高趋势，但未达到显著水平。出现上述脑电变化者临床疗效好，反之则临床疗效差。判别分析结果显示，ＱＰＥＥＧ对氯氮平近期临床疗效的预测基本可靠，预测分组正确率为８６％～１００％。     

动态脑电图对32例晕厥患者的监测分析

目的：观察动态脑电图（ＡＥＥＧ）对晕厥患者监测的阳性率,并与常规脑电图（ＥＥＧ）、ＣＴ进行对照观察。方法：应用ＡＥＥＧ、ＥＥＧ和ＣＴ对晕厥患者进行检查。结果：３２例晕厥患者ＡＥＥＧ监测结果,１６例异常,阳性率为５０％,ＥＥＧ异常３例,阳性率为１１．５％;头ＣＴ检查２例异常,阳性率为６．３％。结论：ＡＥＥＧ对晕厥监测阳性率明显高于ＥＥＧ及ＣＴ。对晕厥患者中不典型及睡觉中亚临床癫痫发作提供了诊断与鉴别诊断依据。     

安定静脉注射后脑电图变化鉴别脑肿瘤的观察

目的：探讨安定静脉注射后脑电图（ＥＥＧ）变化鉴别脑肿瘤的价值。方法：对大脑半球肿瘤组１３例以及对照组（为非肿瘤性疾病,如脑血管病、脑炎）２２例进行安定静脉注射,比较注射前后ＥＥＧ改变。结果：安定静脉注射后,脑肿瘤区δ、θ慢波指数、频率、波幅无明显变化,慢波上一般不增加快波;脑血管病和脑炎则反之。结论：安定静脉注射ＥＥＧ改变对脑肿瘤的鉴别及其定位有重要参考价值,弥补了常规ＥＥＧ之不足。     

A retrospective study of clozapine and electroencephalographic abnormalities in schizophrenic patients

This study investigated the incidence and nature of clozapine-associated electroencephalographic (EEG) abnormalities and the relationship between EEG abnormality and clozapine dosage in Korean schizophrenic patients. Fifty schizophrenic patients with normal baseline EEG and with additional EEG record examined during clozapine treatment more than once were included. Thirty-one patients (62%) showed abnormal EEGs after clozapine treatment, and two of them had seizures. The majority of EEG abnormalities presented as nonspecific slow waves (SW). Spikes (or spike and wave complexes; SP) and frontal intermittent rhythmic delta activity (FIRDA) were relatively rarely observed. The probability of EEG abnormality was linearly dependent on the daily dose of clozapine and patient's age. Our results can be summarized as follows: (1) a substantial proportion of Korean patients treated with clozapine develops EEG abnormalities, and its incidence is comparable to the published results in Caucasian patients; (2) EEG abnormalities occurred in a dose-dependent manner; and (3) the occurrence of EEG abnormalities did not necessarily lead to future seizure development, except in a small number of cases.     

Clozapine (Clozaril), seizures, and EEG abnormalities

The antipsychotic agent clozapine (ClozarilE) is reserved for the treatment of refractory psychosis. Clozapine has allowed many schizophrenic patients to lead more independent and productive lives, but its use is restricted by side effects. Clozapine has been shown to lower seizure threshold and produce significant EEG changes. Although not a commonly used drug, both clinical neurophysiology technologists and interpreting electroencephalographers need to be aware of the effects of clozapine on the EEG. We review the findings of two patients who developed neurological symptoms and EEG abnormalities that resolved following reduction of clozapine therapy.     

Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial.

Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopathology. Concomitantly, serum concentrations of clozapine and metabolites were measured during monotherapy and after addition of fluvoxamine. In all patients, the serum concentrations of clozapine and metabolites were markedly increased (average: 2-3 fold, up to 5 fold for clozapine) after addition of fluvoxamine. Side effects remained almost unchanged in frequency and severity in spite of the pharmacokinetic interactions. ECG or laboratory parameters and orthostatic tests were similar under monotherapy and comedication. Minimal increases of EEG abnormalities were observed, but they were not associated with clinical impairment. Epileptic activities were always absent. The psychopathology improved which continued after start of the comedication. Though the addition of fluvoxamine to clozapine medication was well tolerated and critical side effects were absent, the combined treatment should be controlled by drug monitoring, as serum concentrations of clozapine increased to unpredictably high levels. Further studies have to find out if the combined treatment could be advantageous to clozapine monotherapy.     

Non-linear dynamic analysis of clozapine-induced electroencephalographic changes in schizophrenic patients--a preliminary study

1. In order to find the electroencephalographic (EEG) parameters that reflect the effect of clozapine in schizophrenic patients, the authors applied various non-linear analyses on multi-channel EEG data drawn from patients before and after a therapeutic trial of clozapine. 2. The correlation dimension was difficult to extract from our limited time series EEG data and the authors did not find a meaningful association with clozapine use. The primary Lyapunov exponent could be reliably calculated but also did not reflect the effect of clozapine. 3. However, the mutual cross-prediction (MCP) algorithm showed potentially meaningful results. The driving system was shifted to the frontal channels after a 4-week trial with clozapine. Moreover, MCP might have a value as a predictor of treatment response. 4. Although preliminary in nature, the MCP might have greater power for interpreting complex changes from channel to channel in EEG induced by clozapine.     

Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.

BACKGROUND: The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest. METHODS: The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the "noninferiority" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total). RESULTS: Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the "noninferiority" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients. CONCLUSIONS: Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.     

The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study

Based on the evidence that lamotrigine added to clozapine in refractory schizophrenic patients has reported promising results, the present 24-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 200 mg/day of lamotrigine or a placebo. A final sample of fifty-one patients completed the study. The results obtained indicate that lamotrigine added to stable clozapine treatment showed a beneficial effect on the negative, positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients. Regarding cognitive functions, improvement was observed in some explored areas, such as attentional resistance to interference, verbal fluency and executive functioning. The findings provide evidence that lamotrigine augmentation of clozapine treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant schizophrenia.     

Combination of clozapine and amisulpride in treatment-resistant schizophrenia--case reports and review of the literature

BACKGROUND: The clinical outcome of patients suffering from schizophrenic psychoses has been considerably improved by atypical antipsychotics like clozapine and amisulpride. In patients whose symptomatology cannot be ameliorated by monotherapy, it might be necessary to combine two atypical antipsychotics. While clozapine interacts with a variety of neurotransmitter receptors, amisulpride predominantly binds with high affinity to D3/D2-dopamine receptors. Combination can be considered if a supplementary dopamine-receptor blockade is desired. METHODS: We report on the therapy of 15 patients using a combination regimen of amisulpride and clozapine. Data were collected from patient records. The case reports document previous treatment attempts, describe the reason for the combination therapy, and determine its effect. RESULTS: Major (six cases) or at least marked (eight cases) improvement of previously treatment-resistant positive and negative symptoms could be achieved by using a mean clozapine dose of 375 mg/day (serum level 0.38 mg/l) and an amisulpride dose of 527 mg/day. Additionally, by reducing the clozapine dose compared to monotherapy by 24 %, a significant reduction of side effects was observed. CONCLUSIONS: The combination of amisulpride with clozapine considerably enriches the therapeutic arsenal in cases of severe schizophrenic psychoses. Additional prospective studies are needed in order to systematically evaluate this new treatment strategy.     

Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine

The purpose of this study was to investigate immune-inflammatory markers in schizophrenia and the effects of chronic treatment with clozapine, an atypical antipsychotic agent, on these variables. Toward this end, we measured interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R in the blood of 26 normal controls and 14 schizophrenic patients before and after treatment with clozapine. The sIL-2R and IL-6 levels were significantly higher in younger (<35 years) schizophrenic subjects than in normal controls and older (≥ 35 years) schizophrenic subjects. The sIL-6R levels were significantly lower in schizophrenic subjects than in normal controls. Chronic treatment with clozapine significantly increased the blood concentration of sIL-2R; the increases in the latter were significantly related to the dose of clozapine but not to changes in severity of positive or negative symptoms. We conclude that: (a) schizophrenia in younger people is accompanied by increased IL-6 and sIL-2R secretion; and (b) subchronic treatment with clozapine increases sIL-2R levels. Increased plasma sIL-2R may be one mechanism by which neuroleptics exhibit their immunosuppressive effects.     

The effect of sudden clozapine discontinuation on management of schizophrenic patients: A retrospective controlled study

BACKGROUND: The aims of our study were (1) to compare the dose of clozapine needed to achieve remission in patients who stopped their treatment (study group) versus patients who continued taking this medication (control group) and (2) to compare the clinical characteristics of remission between these 2 groups. METHOD: We retrospectively reviewed the medical records of all treatment-resistant schizophrenic and schizoaffective patients (according to DSM-IV criteria) who were treated with clozapine over a period of 9 years, from January 1995 through December 2003. The study group consisted of 43 patients and the control group of 12 patients. All patients' files from both groups were examined, and each patient's remission was scored twice--initially on discharge from the hospital and subsequently after final discharge for the study group, or at the end of the study for the control group. RESULTS: The change of clozapine dose from the first to the last remission expressed by percentage shows a significant difference between the 43% increase in clozapine dose in the study group and the 12.5% decrease in clozapine dose in the control group (p < .001). Quality of remission assessment showed deterioration in the global remission score in the study group, while the quality of remission assessment in the control group did not show any change. CONCLUSIONS: Our findings suggest that the discontinuation of clozapine treatment leads to a deterioration in the quality of remission, with a need for an increased dose of clozapine. Further prospective studies on larger samples are needed to confirm these findings.     

Clozapine in patients with chronic schizophrenia: serum level,EEG and memory performance

The atypical antipsychotic clozapine causes EEG alterations, and may lead to memory impairments due to its anticholinergic properties. The relationships between clozapine serum level, quantitative EEG parameters and performance in vigilance and memory tasks were studied in a group of 17 chronically ill schizophrenic patients under maintenance treatment with clozapine at stable dosages. There were negative correlations between clozapine serum levels and the amount of high-frequency EEG activity and positive correlations between high-frequency EEG activity and memory performance. These findings may suggest that clozapine treatment brings about dose-dependent impairments of vigilance and memory, for which a reduction of high-frequency EEG activity is indicative.