利培酮合并氯氮平治疗难治性精神分裂症对照研究

目的探讨利培酮联合氯氮平治疗难治性精神分裂症(TRS)的疗效及安全性。方法将63例TRS患者随机分为利培酮合并氯氮平组(治疗组)32例和利培酮组(对照组)31例,两组治疗后4、8、12周均以阳性与阴性症状量表(PANSS)评定疗效,治疗意外症状量表(TESS)评定不良反应。结果治疗组和对照组治疗TRS的疗效比较差异有统计学意义(P<0.05)。治疗后8周,两组PAN-SS总分均较治疗前下降,治疗组下降更明显。两组治疗12周后PANSS总分比较,治疗组明显低于对照组,差异有统计学意义(P<0.05)。结论利培酮联合氯氮平治疗TRS的疗效肯定,值得临床应用。     

阿立哌唑和氯氮平对精神分裂症患者生活质量影响的对照研究

目的探讨阿立哌唑治疗对精神分裂症患者生活质量的影响。方法以阿立哌唑和氯氮平治疗精神分裂症各50例作对照研究,采用阳性和阴性症状量表（PANSS）评定临床疗效,采用副反应量表（TESS）和实验室检查评价安全性,采用WHOQOL—BREF量表衡量患者生活质量。结果阿立哌唑组PANSS总分由治疗前的（92．78±18．69）分降至（41．82±9．62）分,氯氮平组PANSS总分由治疗前的（93．52±18．76）分降至（42．96±8．99）分,与治疗前比较两组均有极显著性差异（P〈0．01）,两组问各时点PANSS总分比较无显著性差异（P〉0．05）,但氯氮平组不良反应较多。经12个月治疗,阿立哌唑组的身心健康分由治疗前的（38．76±8．57）分提高到（72．56±5．64）分,心理健康分由治疗前的（22．53±13．47）分提高到（96．67±10．83）分,社会关系分由治疗前的（18．93±14．62）分提高到（96．52±14．62）分环境因素分由治疗前的（20．13±14．92）分提高到（95．87±10．21）分;氯氮平组身心健康分由治疗前的（39．27±8．78）提高到（70．21±9．06）分,心理健康分由治疗前的（23．16±15．52）分提高到（80．13±10．03）,社会关系分由治疗前的（19．31±14．56）分提高到（80．72±10．56）分,环境因素分由治疗前的（220．89±15．0）分提高到（79．89±10．51）分,两组患者生活质量均较治疗前有极显著性改善（P〈0．05）,在心理健康、社会关系和环境因素方面,阿立哌唑优于氯氮平（P〈0．01）。结论在提高患者生活质量方面,阿立哌唑优于氯氮平,有利于精神分裂症的远期康复。     

Beta-blocker and angiotensin-converting enzyme inhibitor may limit certain cardiac adverse effects of clozapine

Clozapine is contraindicated in patients who experienced cardiac adverse effects during therapy. A young male (34 years old) with clozapine-responsive schizophrenia developed hypokinetic cardiomyopathy during treatment. The decision to resume clozapine therapy and to treat cardiac problems with carvedilol and captopril was made due to the failure of other antipsychotics to control symptoms. He was followed up for 5 years. Significant improvement of psychiatric conditions and persistence of normal left ventricular function were obtained with combination treatment. β-Blockers and ACE inhibitors may allow resumption of clozapine in refractory schizophrenia in whom it was withdrawn for cardiotoxicity. A large-scale investigation may be useful to confirm the present observations.     

Acute or subchronic clozapine treatment does not ameliorate prepulse inhibition (PPI) deficits in CPB-K mice with low levels of hippocampal NMDA receptor density

Introduction The hypo-glutamatergic hypothesis of schizophrenia is based on clinical similarities between schizophrenia and phencyclidine (PCP)-induced psychosis in mentally healthy humans. Sensorimotor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), is impaired in schizophrenic patients. In animals, noncompetitive N-methyl-d-aspartate (NMDA) antagonists such as PCP disrupt PPI in a way that resembles the defect seen in schizophrenia. In a previous study with inbred mouse strains, low PPI levels have been demonstrated in CPB-K mice possessing low levels of hippocampal NMDA receptor densities. The present study was performed to test whether the low magnitude of PPI in CPB-K mice can be reversed by the atypical antipsychotic drug clozapine (CLZ). Results Before any treatment, CPB-K mice displayed a significant (p < 0.001) lower level in PPI and a significant (p < 0.001) higher ASR when compared to BALB/cJ mice known to have high hippocampal NMDA receptor densities. Acute and subchronic effects of a 2-week treatment with CLZ at daily doses of 5 and 10 mg/kg intraperitoneally, respectively, did not reveal any significant alteration of PPI levels in CPB-K mice. Nevertheless, the examination of motor behavior during nonstimulus trials provided a positive control for the drug’s effectiveness. Conclusion In summary, (1) this study confirmed our working hypothesis: Lower levels of hippocampal glutamatergic receptor densities correspond to lower sensorimotor gating in CPB-K mice, and (2) acute or subchronic treatment with CLZ did not elevate low PPI levels in CPB-K mice. Thus, further experiments will concentrate on other antipsychotic drugs to prove the predictive validity of this animal model.     

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

Rationale Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex. Materials and methods The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg⁻¹ day⁻¹ s.c.), clozapine (10 mg kg⁻¹ day⁻¹ s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.). Results Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals. Conclusions The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.     

抗精神病药对血清酶水平的影响

目的：比较氯丙嗪、氯氮平及利培酮对精神分裂症患者血清胆碱酯酶(CHE)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、肌酸激酶(CK)及γ-羟丁酸脱氢酶(HBDH)活性的影响。方法：对单用氯丙嗪(30例)、氯氮平(29例)或利培酮(32例)治疗的精神分裂症患者于治疗前、治疗4、8和12周末分别进行血清酶测定及对比分析。采用阳性和阴性症状量表(PANSS)评定疗效。结果：氯丙嗪、氯氮平及利培酮均可引起精神分裂症患者AST、CK及HBDH活性明显下降，氯丙嗪组和氯氮平组下降更明显。氯丙嗪、氯氮平均可引起精神分裂症患者LDH活性明显下降。结论：氯丙嗪、氯氮平及利培酮均可影响精神分裂症患者部分血清酶活性，但这些酶活性的改变不能说明精神分裂症发病和严重程度，也不能作为抗精神病药疗效指标。     

A Case of Clozapine Induced Acute Renal Failure

There have been a few case reports that clozapine, an atypical antipsychotic, caused acute renal failure of interstitial type. Here we report a case of a 38-year-old Korean male patient with treatment-resistant bipolar I disorder who developed acute renal failure after the initiation of treatment with clozapine. We describe the clinical and laboratory findings of the case and discuss the measures for early detection of this life threating condition. Within our knowledge, this is the first report of clozapine-induced acute renal failure in South Korea.     

维思通与氯氮平对精神分裂症认知功能影响的对照分析

目的：比较维思通与氯氮平对首发精神分裂症患者认知功能的影响。方法：将符合入组标准的首发精神分裂症74例随机分为维思通组与氯氮平组，分别进行7周系统治疗，用阳性与阴性症状量表(PANSS)、韦氏成人智力量表(WAIS-RC)、和临床记忆量表(CMS)进行检查，评估其疗效和对认知功能的影响。结果：74例患者在7周治疗后PANSS总分明显下降，但两组之间差异无显著性。维思通组的WAIS-RC、CMS总分均明显高于氯氮平组，差异有显著性。结论：维思通对首发精神分裂症患者认知功能的影响明显好于氯氮平。     

慢性病毒性肝炎对氯氮平血药浓度的影响

目的：探讨不同类型、不同严重程度的慢性病毒性肝炎对氯氮平及去甲氯氮平血药浓度的影响。方法：对92例合并慢性病毒性肝炎（分慢性迁延性肝炎、慢性活动性肝炎两型及轻度、中度、重度三种严重程度）的精神分裂症病人（慢性肝炎组）以及40例无肝脏疾病的精神分裂症病人（对照组），分别于服药2周末、6周末检测氯氮平血药浓度。结果：慢性肝炎组与对照组氯氮平浓度有显著差异，去甲氯氮平浓度无显著差异。中度、重度慢性肝炎组及慢性活动性肝炎组与对照组氯氮平浓度均有显著差异，轻度慢性肝炎组及慢性迁延性肝炎组与对照组氯氮平浓度均无显著差异，各型及各严重程度慢性肝炎组与对照组去甲氯氮平浓度均无显著差异。结论：中度、重度慢性肝炎及慢性活动性肝炎对氯氮平浓度的影响明显大于对去甲氯氮平浓度的影响。因此在临床上，对合并不同类型不同严重程度慢性病毒性肝炎的精神分裂症病人使用氯氮平时剂量应相应减少，并有监测氯氮平浓度之必要。