氯氮平和利培酮对精神分裂症患者体质量的影响

目的:探讨氯氮平和利培酮对精神分裂症患者体质量(体重)的影响及相关因素。方法:选择符合国际疾病分类第10版(ICD-10)精神分裂症的诊断标准,空腹血糖正常,无严重躯体疾病,1周内未用任何抗精神病药的住院患者,共计65例,其中利培酮组32例,氯氮平组33例。两组患者于治疗前和治疗6周末分别做葡萄糖耐量试验,测空腹血胰岛素,测量体质量、身高,计算体质量指数(BMI),评定阳性与阴性症状量表(PANSS)。结果:①治疗后体质量增加者氯氮平组24例(占72.7%),利培酮组19例(占59.4%);氯氮平组体质量平均增加2.5kg,利培酮组1.4kg;②氯氮平组体质量增加与进食量增加、胰岛素水平增加和PANSS评分减分率相关(P<0·05),体质量增加者餐后1h血糖升高;③利培酮组体质量增加与年龄、病程显著相关(P<0·05),与基础BMI存在负相关倾向;④两组治疗后均出现糖耐量减低(IGT)和暂时诊断糖尿病(DM)。结论:氯氮平和利培酮均能导致体质量增加,体质量增加更易对糖代谢造成不良影响。     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

阿立哌唑与氯氮平治疗精神分裂症对照研究

目的:探讨阿立哌唑与氯氮平对首发精神分裂症患者的临床疗效及安全性。方法:对64例精神分裂症患者随机分为两组,分别给予阿立哌唑与氯氮平治疗,疗程8周。用阳性与阴性症状量表(PANSS)和副反应量表(TESS)评定疗效和不良反应。结果:两组疗效差异无显著性(P>0.05),阿立哌唑不良反应显著少于氯氮平(P<0.01)。结论:阿立哌唑是一种安全有效的抗精神病药。     

Hemiballismus from a parietal stroke in a Parkinson patient.

Stroke-induced hemiballismus (HB) has been reported to improve motor function in people with Parkinson's disease (PD). We report on a patient who developed HB from a parietal infarct. The HB was improved by very low-dose clozapine but the HB did not improve the parkinsonism. This suggests that HB itself, whether from a lesion in the subthalamic nucleus or elsewhere, is not what improves motor function in PD; instead, the physiological function of the damaged structure is the determining factor.     

氯氮平对51例精神病患者骨髓象的影响

精神病女性患者５１例，服用氯氮平１００－３５０ｍｇ／ｄ，共４２ｄ。２２例骨髓象由用药前的增生活跃变为增生明显活跃，骨髓粒细胞系统所占比例明显增多；２９例无变化。未见骨髓抑制者。     

Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN-DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN-DBS in influencing not only motor but also emotional behaviour.     

缩泉丸治疗氯氮平所致流涎的临床观察

采用双盲法观察缩泉丸治疗氯氮平所致流涎的疗效。缩泉丸治疗组21例,治疗后流涎症状较19例对照组明显减少(P<0.01)。中医辨证分型与缩泉丸治疗关系分析,表明痰湿内阻型和阳虚亏损型疗效最佳。氯氮平血浓度与流涎两者间无相关性(P>0.05)。     

Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

精神分裂症患者氯氮平使用现况调查

目的:了解精神分裂症患者氯氮平的使用现状。方法:按一定的抽样比例,抽取10个省市46家专科医院或综合医院精神科,于2002年4月22日至24日,采用自制问卷对4779例门诊和住院精神分裂症患者进行氯氮平使用情况调查。结果:39.0%(1863/4779)的患者使用氯氮平治疗,平均剂量为(216±133)mg/d;其中41.2%的患者为联合用药,合并使用抗胆碱能药物者为19.2%。与未使用氯氮平的患者比较,使用氯氮平的患者病程较长、家庭收入较低;男性及住院患者更多使用氯氮平,氯氮平治疗者疗效指数低于非氯氮平治疗者。患者的性别、就诊部门、家庭收入和是否首次住院以及抑郁和攻击症状为是否使用氯氮平治疗的影响因素。结论:精神分裂症患者氯氮平使用率为39.0%,其中41.2%为联合用药。是否使用氯氮平治疗与患者的经济状况和临床特征等因素有关。     

Endogenous kynurenic acid disrupts prepulse inhibition.

BACKGROUND: Recent studies show that endogenous levels of kynurenic acid (KYNA) are increased in the cerebrospinal fluid of schizophrenic patients. Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating that is reduced in neuropsychiatric disorders, such as schizophrenia. Previous studies show that administration of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine or MK-801, leads to deficits in sensorimotor gating that mimic those observed in schizophrenic patients. METHODS: The present study examined the effects of the endogenous NMDA receptor antagonist KYNA on startle and PPI in rats. Elevation of endogenous brain levels of KYNA was achieved through intraperitoneal (IP) administration of kynurenine (100 mg/kg), the precursor of KYNA, or by intravenous administration of PNU 156561A (10 mg/kg). RESULTS: A fourfold increase in brain KYNA levels, as induced by kynurenine or PNU 156561A, significantly reduced PPI. There were no differences in startle magnitudes between control rats and drug-treated rats. The disruption of PPI was restored by administration of the antipsychotic drugs haloperidol (.2 mg/kg, IP) or clozapine (7.5 mg/kg, IP). CONCLUSIONS: The present results suggest that brain KYNA serves as an endogenous modulator of PPI and are consistent with the hypothesis that KYNA contributes to the pathophysiology of schizophrenia.