利培酮、氯氮平与氯丙嗪的疗效和不良反应及相关因素的研究

目的　比较利培酮、氯氮平与氯丙嗪的疗效和不良反应 ,探讨有关的实验室检查和药物浓度相互关系。方法　将符合CCMD 2 R诊断标准的精神分裂症患者 ,根据临床情况和入院顺序 ,分别进入利培酮组、氯氮平组与氯丙嗪组 ,观察 8周。以PANSS、CGI、TESS和ESRS量表评定药物的疗效和不良反应。同时测定血清泌乳素和药物浓度。结果　治疗 8周后 :①利培酮组、氯氮平线和氯丙嗪组的PANSS量表总分、阴性分量表、一般精神病理学分量表和CGI量表病情严重程度评分均下降 ,而利培酮组和氯氮平组减分较氯丙嗪组明显 (分别P <0 0 1,P <0 0 5 ) ,TESS及ESRS量表的评分也与氯丙嗪组有显著性差异 (分别为P <0 0 1,P <0 0 5 )。②利培酮组、氯氮平组与氯丙嗪组肝功能、心电图检查组间差异有非常显著意义 (均P <0 0 1)。③氯氮平的剂量与去甲氯氮平、氯氮平浓度呈显著相关 ,9 羟利培酮浓度与PRL、利培酮有效率呈显著性相关 ,氯丙嗪浓度与PRL呈显著性相关 (rs=0 .2 6 1,P =0 .0 15 )。结论　利培酮、氯氮平具有较强抗精神病作用 ,相对氯丙嗪更为有效和全面。利培酮的安全性相对较好。     

利培酮、氯氮平对精神分裂症患者心电图的影响

目的研究利培酮与氯氮平引起心电图改变对心脏的影响。方法215例精神分裂症患者在服药前、服药后2、4、8周分别作心电图检查。结果服用利培酮、氯氮平后均可引起心电图改变，其中窭性心动过速、心肌缺血均以氯氮平组显著较多。心电图改变与服药时间、药物剂量有关。结论利培酮引起心电图改变显著少于氟氮平，安全性高。不良反应轻微。     

长期服用利培酮、氯氮平及氯丙嗪对精神分裂症患者心电图和心肌酶的影响

目的 了解长期服用抗精神病药物利培酮、氯氮闰及-平氯丙嗪对精神分裂症患者心电图和心几敏酶的影响.方法 选择符合中国精神障碍分类与诊断标准第三版(CCMD-3)精神分裂症诊断标准,且单用研究药物、治疗时间超过五年的患者作为研究对象,共收集217例,其中服用利培酮60例、氯氮平100例、氯丙嗪57例,检测其心肌酶:包括肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶MB亚型(creatine kinase isozyme-MB,CK-MB)、乳酸脱氢酶(lactate dehydrogenase,LDH)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST),并检测心电图.结果 1、与利培酮组及氯丙嗪组比较,氯氮平组出现心电图异常人数最多,且有统计学差异,其心电图的改变以T波改变及逆钟向转位最为常见;2、心肌酶指标CK-MB在三组患者之间存在统计学差异(P<0.01),其中氯氮平组明显高于利培酮组与氯丙嗪组.结论 长期服用利培酮、氯氮平、氯丙嗪对精神分裂症患者的心肌酶和心电图可产生一定的影响,以氯氮平组变化最为显著.     

利培酮、氯氮平、氯丙嗪长期治疗对糖脂代谢的影响

目的了解利培酮、氯氮平、氯丙嗪长期治疗后糖脂代谢的情况及其之间的差别。方法检测42例利培酮、76例氯氮平、40例氯丙嗪单一治疗连续2年以上的精神分裂症患者的简易体质参数、空腹血糖和血脂,并与63例健康对照者的资料进行比较。结果利培酮、氯氮平、氯丙嗪治疗期间新出现的糖尿病病例数分别为2例、8例、2例,氯氮平组较多,但3组间无统计学差异(P>0.05)。氯氮平组BM I大于对照组、氯丙嗪组,腰围及腰臀比利培酮组、氯氮平组均大于对照组和氯丙嗪组(P<0.05或P<0.01);氯氮平组TG值大于对照组及氯丙嗪组(P<0.01),利培酮组、氯氮平组、氯丙嗪组HDL-ch、ApoA1值均小于对照组(P<0.05或P<0.01),两两比较利培酮组HDL-ch、ApoA1值大于氯氮平组及氯丙嗪组(P<0.01)。TG/HDL-ch值氯氮平组大于对照组(P<0.01)和氯丙嗪组(P<0.05)。TC/HDL-ch值三组均大于对照组(P<0.01),但三组间无明显差异。ApoB值三组与对照组相比无明显差异(P>0.05)。结论利培酮、氯氮平、氯丙嗪长期治疗的精神分裂症患者存在一定糖脂代谢紊乱,并且三者对糖脂代谢的影响存在一定差异,氯氮平治疗组脂代谢异常更明显,值得临床重视。     

三种抗精神病药物对心电图QT间期影响的对照研究

目的探讨喹硫平、利培酮、氯氮平对精神分裂症患者心电图QT间期的影响。方法将120例住院精神分裂症患者随机纳入喹硫平组、利培酮组及氯氮平组,每组40例。于入组前、用药第2、4周进行心电图检查,并对QT间期结果进行比对分析。结果使用药物后三组间QT间期差异有统计学意义,各组前后差异也具有统计学意义。结论在使用抗精神病药物时,尤其是初期应注意心电图的变化。     

利培酮与氯氮平对心电图影响的对照研究

目的　研究利培酮与氯氮平对心电图影响的差异。方法　使用ECG— 90 2 0机检查 6 0例服用利培酮和 30例服用氯氮平的精神分裂症患者的心电图变化 ,并对结果进行分析。结果　服用利培酮后心电图变化异常率为 11 7% ,服用氯氮平后心电图变化异常率为 4 3 3% ,二者有显著差异 (P <0 .0 1)。结论　提示利培酮对心脏的毒性副作用明显低于氯氮平。     

利培酮对心电图的影响

目的研究利培酮引起心电图改变的特征及其与服药时间、剂量之间的关系,并与氯氮平引起的心电图改变作比较.方法对符合CCMD-2-R诊断标准的精神分裂症、分裂样精神障碍患者,在服药前、服药后4周、8周分别作心电图检查,记录服药剂量与心电图改变的情况,并在利培酮组与氯氮平组之间作显著性检验.结果利培酮引起的心电图改变主要为窦性心动过速、T波变化,其程度及发生率均低于氯氮平,一般不影响治疗.并且与服药天数、剂量大小有一定的关系.结论利培酮可引起心电图的改变,其程度及发生率低于氯氮平.     

利培酮与氯氮平治疗精神分裂症对心电图的影响

目的 探讨利培酮、氯氮平分别对心电图的影响。方法 对服用利培酮及氯氮平治疗的精神分裂症病人分别定期心电图检查,时间为服药后第１２、４、８周。结果 利培酮６７次（１２．４１％）,氯氮平３６３次（５９．７０％）出现异常,两者有显著性差异（Ｐ〈０．０５）。结论 利培酮对心电图影响显著低于氯氮平。     

利培酮及氯氮平对治疗精神分裂症患者血清Leptin浓度影响的初步研究

目的探索精神分裂症患者服用氯氮平或利培酮后血清Leptin浓度的变化及其与体重变化的关系.方法(1)用放射免疫分析法测定这两组患者血清Leptin的基线、服药1月、服药2月的浓度.(2)测量两组患者的基线及服药后1月、2月体重.结果(1)两组患者血清Leptin水平在服药1月后均有显著性增高,服药1月和服药2月后Leptin水平变化差异不显著.(2)两组患者的体重指数在服药后也均有显著增加.(3)氯氮平与利培酮两种药物引起Leptin浓度变化和体重指数无显著性差异.结论服用利培酮及氯氮平1月内患者血清中的Leptin水平呈现显著性增高,之后趋于平缓.     

氯氮平、利培酮对心电图QT离散度的影响

目的探讨氯氮平、利培酮对心电图QT离散度(QTd)的影响及QTd对猝死的预防价值。方法取氯氮平、利培酮两研究组和正常对照组各200例,研究组分别于治疗前、治疗后4周测心电图QT间期各一次。结果研究组治疗前的QTd及校正后的QTcd与正常对照组比较均无显著性差异(P>0.05);氯氮平组治疗前、后QTd、QTcd变化的自身比较,均有显著性差异(P<0.01);利培酮组治疗前、后QTd、QTcd变化的自身比较,均无显著性差异(P>0.05)。结论氯氮平对心电图QTd、QTcd有明显的影响,利培酮对心电图QTd、QTcd无明显影响。     

Coadministration of clozapine and fluvoxamine in psychotic patients--clinical experience.

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clinical study to gather experience in necessary dosages, plasma levels, side effects and clinical efficiency of the coadministration of the two drugs. Eighteen psychotic patients were studied. 50 mg FLUVOX were given throughout the study period, while the CLOZ dosage was increased individually (week 5: 96.9+/-37.2 mg). After 5 weeks the plasma concentrations were as follows: CLOZ 252+/-174 ng/ml, N-desmethylclozapine (DM-CLOZ) 143+/-74 ng/ml and clozapine N-oxide (CLOZ N-OX) 30+/-14 ng/ml. There were no differences in side effects, especially sedation, after 5 weeks compared to the pretreatment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The BPRS scores dropped continuously until week 5 (pretreatment: 53.3+/-13.4; week 5: 33.2+/-12.9) and 5 patients were considered treatment responders (BPRS reduction > 50%). Ten patients continued the combination treatment after the study period and 9 of these patients were in clinical remission when discharged. Given strict therapeutic drug monitoring, coadministration of FLUVOX and CLOZ seems to be a safe and efficient treatment strategy with a low occurrence of the side effects associated with CLOZ treatment. This might be due to additive effects of the two drugs and/or metabolic interaction.     

The effect of typical and atypical antipsychotic drugs on the stimulation of phosphoinositide hydrolysis produced by the 5-HT3 receptor agonist 2-methyl-serotonin

The atypical antipsychotic drug clozapine (CLOZ) and a structurally related compound RMI 81,582 (RMI) dose-dependently inhibited the stimulation of phosphoinositide hydrolysis induced by the 5-HT₃ receptor agonist 2-methyl-serotonin in the rat fronto-cingulate and entorhinal cortices. The antagonism of 2-methyl-serotonin's stimulation of phosphoinositide hydrolysis by CLOZ and RMI was comparable to that observed with 5-HT₃ antagonists such as granisetron, ondansetron, ICS 205–930 and zacopride. By contrast, the typical antipsychotic drugs haloperidol (HAL) and chlorpromazine (CPZ) did not antagonize the stimulation of phosphoinositide hydrolysis induced by 2-methyl-serotonin. The 5-HT₃ receptor antagonizing effect of CLOZ and RMI may contribute to the ‘atypical’ pharmacological profile of these antipsychotic drugs.     

安坦对氯丙嗪血药浓度的影响—─短期和长期服药病人的比较

以短期和长期服用氯丙嗪的精神分裂症病人为对象，比较合并安坦后两组氯丙嗪血药浓度变化的差异。根据以往连续服用氯丙嗪≤１年或≥５年，将样本分为短期服药组（１７例）和长期服药组（２１例），给予口服安坦４ｍｇ／日，分别于合并安坦前、合并后２周、４周测定氯丙嗪血药浓度。结果发现短期服药组氯丙嗪血药浓度有显著下降（Ｆ＝４．０７，Ｐ＜０．０５），长期服药组无显著下降（Ｐ＞０．０５）。在降低幅度＞２０％的病例中，短、长期服药组分别占４１．２％和９．５％（χ２＝５．６１，Ｐ＜０．０１）。相关分析结果，氯丙嗪血药浓度下降幅度与以往服药期呈显著负相关。可见安坦降低氯丙嗪血药浓度的作用仅在以往服药期较短或部分急性病人当中显得较为明显，而长期服药病人合并安坦后氯丙嗪血药浓度无显著变化     

抗精神病药过量对心电图的影响

目的：探讨抗精神病药过量对心电图的影响。方法：对吞服过量抗精神病药自杀患者和服用常规剂量抗精神病药患者的心电图进行对照分析。结果：抗精神病药过量组患者的心电图异常的严重程度显著高于常规剂量组。药物过量所致心电图异常率高低和严重程度与服药后至开始抢救的间隔时间长短密切相关。结论：抗精神病药过量导致心电图异常严重程度较高，应引起重视。     

A clinical study of emergent anxiety in neuroleptic-na?ve, first-episode schizophrenia patients following treatment with risperidone]

Risperidone (RIS) alone was administered to patients with neuroleptic-na?ve, first-episode schizophrenia who visited the outpatient clinic of the Department of Psychiatry, Jikei University School of Medicine Hospital between April 1998 and December 2001, and the effectiveness of the drug in alleviating anxiety symptoms was prospectively examined. The study population comprised 42 patients (24 males and 18 females). Their mean age at first visit was 26.0 +/- 6.5 years, DUP (Duration of Untreated Psychosis) was 41.1 +/- 60.0 weeks, and the mean total BPRS (Brief Psychiatric Rating Scale) score at first visit was 60.5 +/- 8.5 points. The rating "effective" (a total BPRS score improvement at week 8 of 50% or more) was given to 32 out of the 42 patients (76.2%). Among these 32 patients, a 25% improvement in the PANSS (Positive and Negative Syndrome Scale) positive scale was achieved at 1. 53 +/- 0.72 weeks and a 50% improvement at 2.93 +/- 2.10 weeks, suggesting early onset of the effects of RIS. The present study focused on the anxiety complained of by some of the patients in whom treatment was rated as effective (increase of 2 points in anxiety BPRS score), dividing these patients into an anxiety group and a non-anxiety group. The anxiety group comprised 17 patients (53.1%). The anxiety observed during the course of treatment with RIS tended to develop early after the disappearance of positive symptoms. A comparison of demographic factors and GAF between the two groups revealed a significant difference in mean age at first visit, DUP and GAF score, the anxiety group tending to be younger, to have shorter DUP and to have social dysfunction compared to the non-anxiety group. Although it cannot be concluded that these anxiety symptoms are characteristic of risperidone, the effect of chemotherapy with other atypical antipsychotic drugs remains as an interesting theme for future investigation.     

Differential effects of typical and atypical antipsychotics on nerve growth factor and choline acetyltransferase expression in the cortex and nucleus basalis of rats

Previously we reported that chronic exposure to haloperidol (HAL), but not the atypical antipsychotics risperidone (RISP) or clozapine (CLOZ), resulted in reductions in brain choline acetyltransferase (ChAT) immunoreactivity and impaired water maze task performance in rats. In the present study, we compared the effects of these antipsychotic drugs on the expression of nerve growth factor (NGF) as well ChAT the in the rat cortex and nucleus basalis of Meynert (NBM) in an effort to determine the underlying mechanism for the differential drug effects observed previously. We also evaluated the effects of these compounds in a crossover design to evaluate specific neurochemical consequences of switching between typical and atypical antipsychotics, a common practice observed in the clinical setting. Male Wistar rats (250-300 g) were exposed to HAL (2.0 mg/kg/day), RISP (2.5 mg/kg/day), or CLOZ (20 mg/kg/day) for 45 days or a pre-treatment regimen consisting of administering either RISP/HAL (i.e., RISP followed by HAL) or CLOZ/HAL, or a post-treatment regimen consisting of administering: HAL/RISP or HAL/CLOZ. The duration of each treatment in the crossover study was also 45 days. NGF and ChAT immunoreactivity were measured by quantitative immunohistochemistry in some sub-cerebral cortical regions and NBM after drug exposures. NGF protein was also measured by an enzyme-linked ImmunoSorbent assay (ELISA) in rat sensorimotor cortex. The results indicated that HAL (but not RISP or CLOZ) significantly reduced NGF levels in some sub-cortical regions and ChAT immunoreactivity in both cortex and NBM. However, pre-treatment with CLOZ prevented the HAL-associated decreases in NGF and ChAT, while post-treatment with either RISP or CLOZ (i.e., after the administration of HAL) appeared to restore NGF and ChAT to control levels. These data indicate that antipsychotic drugs exert dissimilar effects on the levels of NGF and ChAT in the brain, which may contribute to their differential effects on cognitive function. The crossover data further suggest that certain atypical antipsychotic drugs (e.g., clozapine) may have the potential to prevent or reverse the deleterious effects of HAL on important neurochemical substrates of cognitive function.     

Double-blind comparative clinical trial of pimozide and chlorpromazine in mania

Pimozide (PMZ), a relatively specific dopamine (DA) receptor blocking drug, was compared to chlorpromazine (CPZ) in a double-blind, between-patient clinical trial in mania. The trial lasted 14 days. Twenty-three patients who fulfilled Feighner's criteria for mania entered the trial (one patient entering on two separate occasions). Both drugs led to clinical improvement, with a significant effect being noted within 24 hours. According to one of the two rating scales used, initial improvement was greater with chlorpromazine, probably due to its greater sedative effect. By 7 days both drugs were equally effective. Sedative side effects were more frequent in patients on CPZ; extrapyramidal side effects were more frequent with PMZ. The finding that the relatively specific DA receptor blocking drug PMZ was as effective as CPZ in the treatment of mania is consistent with the view that hyperactivity of central DA pathways is involved in the pathogenesis of this condition.     

Update on the clinical efficacy and side effects of clozapine

Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.     

精神疾病患者猝死前心电图分析

目的：探讨精神疾病患者猝死前心电图特征及其相关影响因素。方法：将临床诊断为心脏性猝死的49例患者作为猝死组；随机抽出同期住院的60例患者作为对照组。比较两组患者心电图特征，人口学资料以及临床特征。结果：猝死组心电图异常发生率显著高于对照组（P〈0．05），主要表现为窦性心动过速、室性期前收缩、QT间期延长、T波改变、ST段低平、U波或TU融合波、左束支传导阻滞（LBBB）。猝死组氯氮平使用率显著高于对照组（P〈0．05）。两组使用氯氮平者心电图异常率明显高于未使用氯氮平者（P〈0．05或P〈0．01）。猝死组高龄，兴奋状态，低血钾，肌酸激酶升高，心脑血管疾病的发生率均显著高于对照组（P均〈0．05）。结论：精神疾病患者猝死前大多心电图异常，多呈非特异性改变。高龄、使用氯氮平以及某些临床征象可能成为患者猝死的危险因素。     

Rapid improvement of tardive dyskinesia with tetrabenazine,clonazepam and clozapine combined: a naturalistic long-term follow-up study

Tardive dyskinesia (TD) is a complex involuntary movement disorder affecting about 23% of neuroleptic-treated patients. Our objective was to retrospectively analyze a combination of tetrabenazine (TBZ), clonazepam (CLONAZ) and clozapine (CLOZ) used simultaneously for TD in psychotic patients. Six patients with severe, unsuccessfully controlled TD were referred for treatment (mean age 51.5 years; three male; four schizophrenics; one bipolar disease; one borderline personality disorder). They were being treated with neuroleptics (classic, three; risperidone, two; olanzapine, one) and developed severe neck and buccolingual dyskinesias. At our clinic, all of them were treated simultaneously with TBZ (mean dose 141.6 mg); CLONAZ (mean dose 4.3 mg); and CLOZ (mean dose 125 mg). In parallel, we stopped the offending medication. With 1 week, we observed a very impressive improvement in symptoms and within 1 month all the patients were free of symptoms. The mean observation period was 4 years. The combination of TBZ, CLONAZ and CLOZ is a rapid and beneficial option for the management of TD. An augmentation effect probably played a role in the rapid alleviation of symptomatology.