齐拉西酮与奥氮平治疗早期精神分裂症的临床效果比较

目的 探讨齐拉西酮和奥氮平对于治疗早期精神分裂症的临床疗效及比较两者的安全性。方法 选取我院2017年9月～2019年2月收治的60例早期精神分裂症患者作为研究对象,采用数字随机法将所有患者分成对照组30例和观察组30例,对照组给予奥氮平治疗,观察组给予齐拉西酮治疗。2周为1个疗程,两组均进行8周4个疗程治疗。比较两组患者于治疗前和治疗后2、4、8周进行阳性和阴性症状量表(PANNS)评分,病情严重程度(SI)、疗效总评(GI)评分和不良反应。结果 治疗2周、4周后,两组患者的PANSS评分和SI、GI评分均较低于治疗前,但两组的PANSS评分和SI、GI评分比较,差异无统计学意义(P0.05);疗程结束后,观察组的患者PANSS评分和SI、GI评分均低于对照组,差异有统计学意义(P0.05);治疗期间,对照组的不良反应发生率高于观察组,差异有统计学意义(P0.05)。结论 对于治疗早期分裂症患者,齐拉西酮的长期治疗效果明显优于奥氮平,且安全可靠,值得临床上进一步推广。     

利培酮和齐拉西酮对精神分裂症患者血浆细胞因子的影响

目的:研究抗精神病药对精神分裂症患者细胞因子的影响。方法:符合ICD-10精神分裂症诊断的60名患者,随机分为利培酮组(给予利培酮治疗)和齐拉西酮组(给于齐拉西酮治疗),并以健康对照组比较,对患者在治疗前及治疗8周后测量血浆IL-2、IL-6及TNF-α水平,并对患者进行PANSS量表评定。结果:两组患者治疗前后血浆IL-2、IL-6及TNF-α水平与对照组比较,差异有统计学意义(P0.05)。两组患者治疗后血浆IL-2、IL-6及TNF-α水平较治疗前降低,差异有统计学意义(P0.05)。治疗前IL-2水平与PANSS量表阳性症状评分呈正相关(r=0.54,P0.05)治疗后TNF-α与阴性症状分呈显著正相关(r=0.41,P0.05)。结论:精神分裂症患者存在免疫功能异常,利培酮和齐拉西酮可以降低精神分裂症患者细胞因子水平。细胞因子水平与精神病理存在一定相关性。     

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors

The atypical antipsychotic olanzapine was compared to other atypical as well as typical antipsychotic agents for in vivo occupancy of D₁, D₂, D₃, 5HT₂, and muscarinic receptors in rat brain. Blockade of D₂ receptors was determined by measuring the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). To assess the interaction with phosphoinositide (PI)-coupled 5HT_2A and muscarinic receptors in vivo, we used a novel radiometric technique to measure in vivo PI hydrolysis. The antagonism of olanzapine and other antipsychotic agents on 5HT_2A and muscarinic receptors was determined by in vivo blockade of PI hydrolysis, stimulated by the 5HT₂ agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) or the muscarinic agonist pilocarpine. Olanzapine inhibited 5HT₂, D₂, and D₃ in vivo binding with high potency (ID₅₀ = 0.15, 0.6 and 1.2 mg/kg, IP, respectively), while inhibiting D₁ and muscarinic in vivo binding with much less potency (ID₅₀ > 10 mg/kg, IP). The binding of olanzapine to D₂ receptors in neostriatum was well correlated with the increase of DOPAC (ED₂₀₀ = 0.8 mg/kg, IP) in vivo, indicating dopamine D₂ antagonism. In vivo PI hydrolysis was increased by DOI in frontal cortex and by pilocarpine in hippocampus up to 2- and 7-fold above the basal level, respectively. The agonist-induced increases in PI hydrolysis were fully blocked by the 5HT_2A antagonist MDL100907 and the muscarinic antagonist scopolamine, indicating the mediation by 5HT_2A receptors in frontal cortex and PI-coupled muscarinic receptors (m1, m3, and m5) in hippocampus, respectively. Olanzapine was about 8-fold more potent in vivo in blocking DOI-induced stimulation of PI hydrolysis (ID₅₀ = 0.1 mg/kg, IP) than pilocarpine-induced stimulation of PI hydrolysis (ID₅₀ = 0.8 mg/kg, IP). In conclusion, olanzapine is more potent in blocking the 5HT_2A receptor than D₁, D₂, D₃ and muscarinic receptors in vivo, consistent with its favorable clinical profiles. In addition, the novel in vivo PI hydrolysis assay proved to be a useful and reliable in vivo method to assess the functional efficacy of compounds that interact with the 5HT₂ and muscarinic receptors. Received: 10 February 1998/Final version: 22 April 1998     

国产齐拉西酮与奎硫平治疗精神分裂症双盲对照研究

目的 了解国产齐拉西酮与奎硫平治疗精神分裂症的疗效和安全性.方法 筛选出186例精神分裂症患者,采用随机双盲方法,将其分为2组,分别以齐拉西酮(n=93)与奎硫平(n=93)治疗6周,分别于治疗前及疗后1、2、4、6周末以阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)评定疗效,以不良反应量表(TESS)评定副反应.结果 疗后6周末,2组PANSS总分较治疗前均显著下降(P<0.01),PANSS减分率齐拉西酮组为(64.63±17.23)%,奎硫平组为(69.57±24.21)%,2组比较差异无统计学意义(P>0.05);临床总有效率齐拉西酮组为80.00%,奎硫平组为80.68%,2组差异无统计学意义(P>0.05);2周末起临床总体印象量表评分2组均下降明显,与治疗前比较具有统计学差异(P<0.05).2组间不良反应的发生率比较差异无统计学意义(P>0.05).结论 国产齐拉西酮治疗精神分裂症的疗效及副作用与奎硫平相似,是一种有效、安全的抗精神病药物.     

齐拉西酮与利培酮治疗女性精神分裂症对照研究

目的:比较齐拉西酮与利培酮治疗女性精神分裂症患者的疗效及不良反应。方法:将60例女性精神分裂症患者随机分成两组,分别给予齐拉西酮与利培酮治疗8周。采用阳性症状与阴性症状(PANSS)及不良反应量表(TESS)于治疗前及疗后2、4、8周末评估疗效和不良反应。结果:两组有效率分别为83.33%和86.67%,无显著差异(P>0.05),两药治疗女性精神分裂症疗效相当;齐拉西酮较少引起锥体外系反应(EPS),较少出现月经周期的改变。结论:齐拉西酮疗效和利培酮相当,且不良反应轻,是治疗女性精神分裂症患者的较好选择。     

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.     

齐拉西酮与利培酮治疗首发精神分裂症的疗效和安全性

目的观察齐拉西酮与利培酮对首发精神分裂症患者的治疗效果和不良反应,以更好地为精神分裂症患者进行治疗。方法选择2010年8月-2012年8月广州市脑科医院收治的首发精神病患者64例为研究对象,随机分为两组。对照组给予利培酮治疗,实验组给予齐拉西酮治疗,对比观察两组疗效和不良反应。结果实验组患者经治疗,其PANSS优于对照组患者,组间比较差异有统计学意义(P<0.05);实验组不良反应发生率明显低于对照组(32例患者共发生14例),组间比较差异有统计学意义(P<0.05)。结论使用齐拉西酮对首发精神病患者进行治疗可取得更好的治疗效果,且患者不良反应少,值得临床推广应用。     

齐拉西酮和奥氮平治疗精神分裂症的疗效及对认知功能的影响

目的探讨齐拉西酮和奥氮平治疗精神分裂症的疗效及对认知功能的影响。方法选取住院治疗的精神分裂症患者76例,随机分为观察组与对照组。观察组患者予齐拉西酮片治疗,先予以20 mg/d,2周内逐渐加至维持量80~160 mg/d;对照组患者予以奥氮平片治疗,先予5 mg/d,2周内逐渐加至维持剂量10~20 mg/d。两组疗效均为8周。观察两组患者治疗前与治疗8周后认知功能指标的变化,并比较其临床疗效和安全性。结果治疗8周后,两组患者MMSE评分和WMS评分较治疗前明显上升(P0.05或P0.01),且观察组患者上升幅度较对照组更明显(P0.05);同时观察组患者临床总有效率明显优于对照组(χ~2=4.15,P0.05);观察组患者TESS评分为(3.47±0.76)分,明显低于对照组的(4.47±0.89)分。两组患者治疗期间血尿常规、肝肾功能及心电图均无明显异常变化。结论齐拉西酮和奥氮平治疗精神分裂症能明显改善其认知功能,具有良好的临床效果及安全性,且前者改善认知功能及临床效果更佳,安全性较高。     

单磷酸阿糖腺苷联合布地奈德治疗小儿毛细支气管炎的临床研究

目的探讨单磷酸阿糖腺苷联合布地奈德治疗小儿毛细支气管炎的临床疗效。方法选取2014年9月—2016年9月沈阳医学院附属中心医院儿科收治的毛细支气管炎患者151例,随机分成对照组(75例)和治疗组(76例)。对照组雾化吸入吸入用布地奈德混悬液,0.5 mg加入生理盐水3 m L,1次/d,10 min/次。治疗组在对照组的基础上静脉滴注注射用单磷酸阿糖腺苷,0.1 g加入5%葡萄糖溶液100 m L中,1次/d。所有患者均治疗1周。观察两组患者临床效果,对比两组治疗前后症状消失时间、住院时间、炎性指标以及不良反应情况。结果治疗后,对照组和治疗组总有效率分别为84.00%和96.05%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后,治疗组患儿的退热时间、湿啰音消失时间、喘息消失时间和咳嗽消失时间以及住院时间均明显短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患儿肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)以及IL-8指标均明显降低(P0.05);且治疗组的降低程度明显优于对照组,两组比较差异有统计学意义(P0.05)。结论单磷酸阿糖腺苷联合布地奈德治疗小儿毛细支气管炎,在临床症状消失时间、住院时间以及炎症因子水平改善方面上均优于单独使用布地奈德治疗,具有一定的临床推广应用价值。     

The Effectiveness of Cross-Tapering Switching to Ziprasidone in Patients with Schizophrenia or Schizoaffective Disorder

Objective

Switching antipsychotics is one useful therapeutic option when the treatment of schizophrenia encounters suboptimal efficacy and intolerability issues. This study aimed to investigate the efficacy and tolerability of cross-tapering switching to ziprasidone from other antipsychotics.

Methods

A total of 67 patients with schizophrenia or schizoaffective disorder were recruited in this 12-week, multicenter, non-comparative, open-label trial. Prior antipsychotics were allowed to be maintained for up to 4 weeks during the titration of ziprasidone. Efficacy was primarily measured using the 18-item Brief Psychotic Rating Scale (BPRS) at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was secondarily measured by the Clinical Global Impression-Severity (CGI-S) scale and the Global Assessment of Functioning (GAF) scale at each visit. Regarding the metabolic effects of switching to ziprasidone, weight, body mass index (BMI), waist-to-hip ratio (WHR), and lipid profile-including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol levels-were measured at each follow-up visit.

Results

The BPRS scores were significantly improved at 12 weeks after switching to ziprasidone (F=5.96, df=2.11, p=0.003), whereas the CGI-S and GAF scores were not significantly changed. BMIs, WHRs, and TG levels were significantly decreased, with no significant changes in other lipid profiles.

Conclusion

Cross-tapering switching to ziprasidone is effective for patients with schizophrenia spectrum disorders. Beyond the efficacy of the procedure, favorable metabolic profiles show that switching to ziprasidone may be helpful for maintenance therapy over an extended period.