齐拉西酮对精神分裂症患者社会功能和生活质量的影响

目的:评价齐拉西酮与氯氮平对首发住院精神分裂症患者社会功能和生活质量的影响。方法:79例精神分裂症患者随机分为齐拉西酮组40例与氯氮平组39例,分别给予口服齐拉西酮与氯氮平治疗12周。以阳性和阴性症状量表(PANSS)、副反应量表(TESS)、社会功能缺陷量表(SDSS)及生活质量综合评定问卷(GQOLI-74)分别评定2组患者的疗效、不良反应、社会功能缺陷和生活质量。结果:治疗后,2组的PANSS总分和各因子分均显著下降(P0.05,0.01),齐拉西酮组阴性症状评分低于氯氦平组(P0.01);SDSS各条目评分2组均明显下降(P0.05,0.01),齐拉西酮组在家庭内外活动、对外界兴趣、社会性退缩、婚姻职能、责任心和计划性6个条目评分明显低于氯氮平组(P0.05,0.01);齐拉西酮组的GQOLI-74总分及躯体维度、心理维度、社会功能维度评分明显高于氯氮平组(P0.01);齐拉西酮组的不良反应发生率明显小于氯氮平组(37.5%与66.7%,P0.01)。结论:齐拉西酮的疗效与氯氮平相当,但副作用小;对患者社会功能和生活质量的改善更明显。     

Comparison of hippocampal G protein activation by 5-HT<Subscript>1A</Subscript> receptor agonists and the atypical antipsychotics clozapine and S16924

This study employed [³⁵S]guanosine 5-O-(3-thiotriphosphate) ([³⁵S]GTPS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT_1A receptors with those of reference agonists at postsynaptic 5-HT_1A receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E_max, values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC₅₀) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT_1A receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT_1A receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [³⁵S]GTPS binding, consistent with partial agonist properties. In [³⁵S]GTPS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT_1A receptors, was more potent in the septum (pEC₅₀~6.5) than in the dentate gyrus of the hippocampus (pEC₅₀~5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 µM) did not enhance [³⁵S]GTPS labelling in any structure, S16924 (10 µM) modestly increased [³⁵S]GTPS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 µM)-stimulated [³⁵S]GTPS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G protein activation at postsynaptic 5-HT_1A receptors in the hippocampus. These data support a role of postsynaptic 5-HT_1A receptors in the functional profiles of certain antipsychotic agents.     

Ziprasidone induces cytotoxicity and genotoxicity in human peripheral lymphocytes

It has been stated that some antipsychotic drugs might cause genotoxic and carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug. However, its genotoxicity and carcinogenicity data are very limited. The cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with 50, 75 and 100?μg/ml of ZIP in the presence and absence of a metabolic activator (S9 mix). Dimethylsulfoxide was used as a solvent control. While the cells were treated with ZIP for 24?h and 48?h in cultures without S9 mix, the cultures with S9 mix were exposed to ZIP for 3?h. ZIP and its metabolites can exert cytotoxic activities due to significant decreases in mitotic index, proliferation index and nuclear division index in the presence and absence of S9 mix. Statistically significant increases in CAs, aberrant cells and MN values in the presence and absence of S9 mix were found in cultures treated with ZIP. While ZIP significantly increased the SCE values in the absence of S9 mix at all concentrations, increased SCE values in cultures with S9 mix were not found to significantly at all concentrations tested. Our results indicated that both ZIP and its metabolites have cytotoxic, cytostatic and genotoxic potential on lymphocyte cultures under the experimental conditions. Further studies are necessary to make a possible risk assessment in patients receiving therapy with this drug.     

帕利哌酮缓释片与齐拉西酮胶囊治疗精神分裂症对照研究

目的：探讨帕利哌酮缓释片与齐拉西酮胶囊治疗精神分裂症的疗效、不良反应及对社会功能的影响。方法：选取2013年1月-2014年1月在本院住院的76例精神分裂症患者,按照随机数字表法将其分为对照组和研究组各38例,对照组给予齐拉西酮胶囊口服,研究组给予帕利哌酮缓释片口服,在治疗前、2周末、4周末、8周末给予PANSS量表评定。在治疗前、治疗8周末给予PSP量表评定。不良反应情况给予TESS量表评定。结果：两组PANSS评分在治疗2周末开始下降．比较差异有统计学意义（P〈0．05）,而两组在治疗前、治疗4周末、治疗8周末比较差异均无统计学意义（P〉0．05）。两组在治疗前的PSP量表评分比较差异无统计学意义（P〉0．05）,而在治疗8周末比较差异有统计学意义（P〈0．05）。结论：帕利哌酮缓释片和齐拉西酮胶囊治疗精神分裂症疗效、安全性相当,帕利哌酮缓释片起效较快,在社会功能恢复方面帕利哌酮缓释片优于齐拉西酮胶囊。     

齐拉西酮与维思通治疗精神分裂症的对照研究

目的比较齐拉西酮与维思通治疗首发精神分裂症的疗效及安全性。方法将60例首发精神分裂症患者随机分为齐拉西酮组30例和维思通组30例,齐拉西酮组剂量范围20-120mg/天,维思通组剂量范围4-6mg/天,疗效8周。采用阳性与阴性症状量表(PANSS)评定临床疗效,副反应量表(TESS)评定药物不良反应。结果齐拉西酮组有效率为86.4%,维思通有效率为84.6%,两药疗效无显著性差异。齐拉西酮组不良反应较维思通组少,其中震颤、静坐不能等锥体外系症状的发生率显著少于维思通组(P<0.01),未出现严重反应。结论齐拉西酮与维思通治疗首发发精神分裂症的疗效相当,某些不良反应较维思通轻而少,尤其适用精神分裂症患者服用,是一种有效、耐受性好的抗精神病药物。     

齐拉西酮治疗老年期精神分裂症的疗效与安全性

目的:观察齐拉西酮治疗老年期精神分裂症的疗效与安全性。方法:将82例老年期精神分裂症分为齐拉西酮组和利培酮组各41例,分别用齐拉西酮及利培酮治疗。于治疗前及治疗第2、4、6周末,采用PANSS量表评定疗效,采用TESS评定不良反应。结果:治疗6周末,齐拉西酮组PANSS总分、阳性症状分、阴性症状分、一般精神病理症状分与治疗前相比差异有显著意义,有效率95%;利培酮组有效率92.5%,齐拉西酮组总体疗效与利培酮组相当。两组不良反应均轻微。结论:齐拉西酮治疗精神分裂症与利培酮疗效相当,不良反应少,安全性好。     

奥氮平与齐拉西酮对女性首发精神分裂症患者的疗效及体重泌乳素的影响

目的：观察奥氮平与齐拉西酮治疗首发女性精神分裂症患者的疗效和对女性患者体重及泌乳素的影响。方法：将98例女性精神分裂症急性发作的患者随机分为奥氮平组（n=48）、齐拉西酮组（n=50）,观察6周。在治疗前及治疗后第2、4、6周采用阳性和阴性症状量表评定疗效,并测量体重及进行实验室检查。结果：女性首发精神分裂症患者初次使用奥氮平、齐拉西酮治疗,总有效率分别为83．3％、78．00％,两组有效率和无效率比较,差异无统计学意义（x2=0．16,P〉0．05）;奥氮平组PANSS总分的改善优于齐拉西酮组（P〈0．05）;治疗后,齐拉西酮组体重及泌乳索未见明显变化（P〉0．05）,奥氮平组体重及泌乳索显著增高（P〈O．01）;奥氮平组体重及泌乳素显著高于齐拉西酮组（P〈O．01）。结论：齐拉西酮和奥氮平对首次接受治疗的女性精神分裂症患者均具有明确疗效,但奥氮平对患者症状的改善略优于齐拉西酮。与奥氮平相比,齐拉西酮对首次治疗的女性精神分裂症的体重及泌乳素几乎没有影响,相比较而言女性患者对齐拉西酮依从性要好。     

齐拉西酮与氯丙嗪治疗精神分裂症对照分析

目的探讨齐拉西酮与氯丙嗪对首发精神分裂症患者的临床疗效及安全性。方法80例精神分裂症患者随机分为2组，分别给予齐拉西酮与氯丙嗪，治疗8周，用阳性与阴性症状表（PANSS）和副作用量表（TESS）评定疗效和不良反应。结果齐拉西酮组疗效优于氯丙嗪组（P〈0．05），齐拉西酮组不良反应显著少于氯丙嗪（P〈0．05）。结论齐拉西酮是一种安全有效的抗精神病药。     

阿立哌唑与齐拉西酮对精神分裂症患者血糖、血脂和体重影响的Meta分析

目的评价阿立哌唑与齐拉西酮对精神分裂症患者血糖、血脂及体重影响的差异。方法计算机检索CBM、中国期刊全文数据库(CNKI)、万方数据库、维普中文科技期刊数据库(VIP),纳入关于阿立哌唑与齐拉西酮对精神分裂症患者血糖、血脂和体重的随机对照试验,由两名作者单独纳入与排除文献、评价质量、提取数据,将数据录入Rev Man 5.1进行Meta分析。结果共纳入6项符合标准的研究,合计样本量586例,其中阿立哌唑治疗组292例,齐拉西酮治疗组294例;Meta分析结果显示:干预结束时阿立哌唑组体质量低于齐拉西酮组[MD=-0.31,95%CI(-0.56,-0.05)],差异有统计学意义(P0.05);干预结束时阿立哌唑组HDL-c高于齐拉西酮组[MD=0.24,95%CI(0.01,0.47)],差异有统计学意义(P0.05);干预结束时两组的LDL-c,FBG,TCH,TG和BMI比较[MD=-0.31~0.19,95%CI(-0.47,0.43)],差异无统计学意义(P0.05)。结论阿立哌唑在改善血脂代谢、降低体重方面比齐拉西酮更占优势,但两者对于糖代谢的影响无差异。     

Treatment with Ziprasidone for schizophrenia patients with OCD

Comorbidity of obsessive–compulsive disorder (OCD) has been observed in about 15% of schizophrenic patients and has been associated with poor prognosis. Therefore, there is a need for specific treatment options for these patients (schizo-obsessive, ScOCD).This is an open, prospective study, aiming to test the efficacy of Ziprasidone (80–200 mg/d) in ScOCD patients and comparing the response to the treatment between stable schizophrenic (N=16) and stable ScOCD (N=29) patients.Treatment effect with Ziprasidone was different in schizophrenic patients when stratified based on OCD comorbidity. Overall, the effect on OCD symptoms (as measured by the Yale Brown Obsessive Compulsive Scale, YBOCS) was found to be bimodal—either no response or exacerbation (for 45% of the patients, n=13) or significant improvement of symptoms (55%, n=16). Those who improved in OCD symptoms, improved also in negative and general schizophrenia symptoms, while ScOCD-unimproved group worsened in all symptoms. Whereas schizophrenic patients without OCD responded in a modest Gaussian distribution, they improved in schizophrenia negative symptoms and in general anxiety.This data suggests that schizo-obsessive disorder is a distinct and complex condition with more than one underlying pathogenesis. Definition of these ScOCD subgroups defined by their response to Ziprasidone might contribute to personalized medicine within the OCD–schizophrenia spectrum. Moreover, this finding suggests that ScOCD may be considered as a special schizophrenic subtype and its inclusion in schizophrenia treatment studies need to be further explored due to its divergent response.