齐拉西酮与利培酮治疗酒精所致精神障碍的疗效观察

目的 比较齐拉西酮和利培酮治疗酒精所致精神障碍的疗效及不良反应.方法 将84例酒精所致精神障碍患者随机分为两组,分别用齐拉西酮与利培酮治疗6用.采用阳性症状与阴性症状量表(PANSS)评定临床疗效,治疗中出现的药物副反应量表(TESS)评定不良反应.结果 齐拉西酮与利培酮治疗6周有效率分别为90.5%和92.92%,疗...     

Evaluating the CANSAS self-report (CANSAS-P) as a screening instrument for care needs in people with psychotic and affective disorders

The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.     

Effects of risperidone, quetiapine and ziprasidone on ethanol withdrawal syndrome in rats

Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.     

齐拉西酮治疗老年精神分裂症的临床研究

目的比较齐拉西酮和奋乃静治疗老年精神分裂症的疗效和安全性。方法将72例老年精神分裂症患者随机分为2组,分别给予齐拉西酮和奋乃静治疗8周。采用阳性与阴性症状量表(PANSS)评定疗效,副反应量表(TESS)评定不良反应。结果治疗8周后,齐拉西酮组与奋乃静组疗效比较差异无统计学意义(P0.05),齐拉西酮组不良反应程度、发生率均少而轻。结论齐拉西酮治疗老年精神分裂症患者疗效好,不良反应相对较小。     

齐拉西酮对首发精神分裂症患者眼动功能和执行功能的影响

目的:探讨齐拉西酮对首发精神分裂症患者眼动功能和执行功能的影响。方法:将79例首发精神分裂症患者随机分为齐拉西酮组(n=42)和利培酮组(n=37),在基线、治疗4周和8周时进行探究性眼球运动测试和威斯康星卡片分类测验(WCST)。结果:1眼动功能显示,治疗8周时两组的凝视点数显著提高(P0.01);反应性探索评分(RSS分),两组在治疗4周、8周时均显著升高(P0.01),而两组之间差异无统计学意义(P0.05);D分值两组治疗4周时显著下降(P0.01),治疗8周时平均降为负分;2WCST测验治疗前两组均存在执行功能障碍,两组间无统计学差异。与基线时相比,齐拉西酮组治疗4周、8周时总测验次数、持续错误数、随机错误数均明显降低(P均0.01),正确反应数和分类完成数均明显提高(P均0.01);利培酮组治疗4周、8周时总测验次数、持续错误数、随机错误数均明显降低(P均0.01),正确反应数和分类完成数均明显提高(P均0.01)。齐拉西酮组与利培酮组对比,治疗4周时随机错误数齐拉西酮组(29.70±10.66)较利培酮组(35.07±12.36)显著降低(t=2.06,P0.05),治疗8周后齐拉西酮组(20.13±7.08)较利培酮组(23.26±6.28)显著降低(t=2.07,P0.05);其余两组无显著性差异。结论:齐拉西酮对首发精神分裂症患者的眼球轨迹运动有显著影响,改善眼动功能,与对照组利培酮相比差异无统计学意义;首发精神分裂症患者存在执行功能受损,齐拉西酮对执行功能具有显著的改善,较利培酮效果显著;齐拉西酮是一种对认知功能有效的抗精神病药物,值得临床广泛应用与推广。     

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。     

齐拉西酮与奥氮平对初诊精神分裂症患者急性期的疗效和代谢影响对比观察

目的：探讨初诊精神分裂症患者分别采用齐拉西酮与奥氮平的治疗措施及对糖脂代谢的影响。方法整群抽取2014年10月—2015年10月该院收治的118例初诊精神分裂症患者作为研究对象,依据入院顺序的单双号法将其随机分为观察组(n=59)与对照组(n=59),观察组患者予以齐拉西酮的治疗措施,对照组患者则予以奥氮平的治疗措施,分别观察两组患者治疗后的临床效果,并观察糖脂代谢指标的变化情况。结果观察组患者的FBS(4.5±0.3) mmol/L、TC(1.2±0.3) mmol/L、TG(4.0±0.4) mmol/L、INS(9.5±1.0×103)μU/L、LDL(2.0±0.2) mmol/L、HDL(1.3±0.2) mmol/L以IRI(1.9±0.3) mmol/L等指标均显著低于对照组,组间比较差异具有统计学意义(P<0.05)。结论初诊精神分裂症患者采用齐拉西酮药物较奥氮平具有更高的临床疗效,值得推广。     

齐拉西酮早期干预对创伤后应激障碍模型大鼠行为的改善作用及机制

目的 观察齐拉西酮早期干预对改良单次延长应激(single prolonged stress and foot shock,SPS&S)模型大鼠行为的改善作用及大脑磷酸化细胞外信号调节激酶(phosphorylated extracellular signal-regulated protein kinase,pERK1/2)表达的影响.方法 24只SD大鼠随机分为对照组、模型组、齐拉西酮组以及齐拉西酮+ U0126组,每组6只.对照组正常饲养;模型组为SPS&S处理组;齐拉西酮组为SPS&S造模结束后,每天灌胃齐拉西酮( 2.5 mg/kg),连续7d;齐拉西酮+U0126组为SPS&S造模结束后,连续7d给予齐拉西酮,并在每次齐拉西酮灌胃后0.5h,腹腔注射U0126(MEK1/2抑制剂)(0.5 mg/kg).各组在处理结束24h后,采用旷场和高架十字迷宫检测大鼠行为表现,并且在行为实验完成后处死大鼠,以蛋白质印迹法(Western blot)检测大脑pERK1/2的表达水平.结果 在旷场实验中,模型组大鼠水平活动度,中央活动次数[分别为(76.23±54.76) cm,(4.60±1.14)次]低于对照组[分别为(343.77±74.22) cm,(12.40±3.36)次]和齐拉西酮组[分别为(274.98±83.56) cm,(12.00±2.92)次],差异有统计学意义(均P＜0.01),而与齐拉西酮+U0126组[分别为(138.14±41.98)cm,(5.00±1.58)次]相比,差异无统计学意义(均P＞0.05).在高架十字测试中,各处理组在大鼠开臂进入次数和停留时间上的差异性与旷场实验的结果一致.Western blot结果显示,模型组pERK1/2的表达水平明显低于对照组和齐拉西酮组,差异有统计学意义(均P＜0.01).结论 齐拉西酮能改善PTSD动物的焦虑样行为,而且这种作用可能是通过上调pERK1/2的表达实现的.     

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.     

齐拉西酮与利培酮治疗难治性精神分裂症对照研究

目的探讨齐拉西酮治疗难治性精神分裂症的疗效及安全性。方法将84例难治性精神分裂症患者随机分为研究组和对照组,分别给予齐拉西酮和利培酮治疗8周,采用PANSS量表和TESS量表评定疗效和不良反应。结果治辽前后齐拉西酮组PANSS减分率为40.08%,有效率为83.33%;利培酮组PANSS减分率为38.56%,有效率为76.19%,两者比较差异无显著性(P>0.05),齐拉西酮组未见严重的不良反应。结论齐拉西酮与利培酮治疗难治性精神分裂症疗效相当,齐拉西酮对认知功能的改善优于利培酮,但两者比较差异无显著性(P>0.05),齐拉西酮治疗难治性精神分裂症具有疗效好、副作用小,病人依从性好的特点。