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     

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。     

齐拉西酮与阿立哌唑治疗以阴性症状为主的精神分裂症对照研究

目的比较齐拉西酮与阿立哌唑治疗以阴性症状为主的精神分裂症的疗效和安全性。方法将66例以阴性症状为主的精神分裂症患者随机分为研究组（齐拉西酮治疗）和对照组（阿立哌唑治疗）,采用阳性和阴性症状量表（PANSS）、阴性症状评定量表（SANS）评定疗效,副反应量表（TESS）评定不良反应。结果治疗8周后,齐拉西酮组痊愈率33.3%,显效率81.8%。阿立哌唑组痊愈率27.3%,显效率78.8%。齐拉西酮组总不良反应发生率为42.4%,阿立哌唑组总不良反应发生率为57.6%。结果显示两组在疗效和不良反应发生率方面差异均无显著性（P〉0.05%）。结论齐拉西酮与阿立哌唑治疗以阴性症状为主的精神分裂症疗效相当,不良反应轻微,两种药物均有疗效好、安全性高的特点。     

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.     

盐酸齐拉西酮在中国健康志愿者中的药代动力学研究

目的评价国产盐酸齐拉西酮胶囊的人体药代动力学特点;初步评价国产盐酸齐拉西酮胶囊的安全性。方法采用HPLC法测定血浆中齐拉西酮浓度。10位男性健康受试者进食时单剂量口服40mg盐酸齐拉西酮胶囊。于服药前及服药后0.5、1、2、3、4、5、6、8、10、12、24、36、48小时采集5m l血样。抗凝处理取血浆,-20℃保存,用于血药浓度的测定。安全性评价包括体检、实验室检查(心电图、血常规、生化常规及尿常规等)及不良事件的记录。结果主要药动学参数:Cm ax为(175.0±63.73)ng/m l;Tm ax为(3.80±1.32)h;MRT为(9.37±1.53)h;t1/2为(6.10±1.65)h;Ka为0.1831±0.0708/h;Kel为0.1219±0.0349/h;Vd为(685.3±325.4)L;C l为(83.30±34.50)L/h;AUC0→t为(1312±261.3)ng/m l/h,AUC0→∝为(1339±261.1)ng/m l/h。药物不良事件主要为嗜睡、口干、头昏、静坐不能、体位性低血压等,程度多为轻至中度,均能在短时间内缓解。结论研究结果显示了国产盐酸齐拉西酮在中国人中药代动力学特点,单剂量口服胶囊40mg是安全的。     

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。     

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.     

齐拉西酮联合小剂量氯氮平对男性难治性精神分裂症患者认知功能的影响

目的：观察齐拉西酮联合小剂量氯氮平对男性难治性精神分裂症患者认知功能的影响及临床疗效、安全性研究。方法：将100例男性难治性精神分裂症患者随机分为两组各50例,治疗组给予齐拉西酮联合小剂量氯氮平治疗,对照组给予氯氮平治疗。两组均于治疗前后采用阳性与阴性症状量表（ PANSS ）、韦氏成人智力量表（ WAIS－RC）、个人与社会功能量表（ PSP）及不良反应发生量表评定认知功能影响及临床疗效与安全性。结果：两组患者在治疗12周后PANSS总分及各因子分均明显下降,且差异具有统计学意义（t＝16．98,P＜0．05）;治疗后,治疗组WAIS－RC评分及PSP评分均显著提高,且两组差异具有统计学意义（t＝4．76,2．54;P＜0．05）;治疗12周后,两组间临床疗效相当,且治疗期间,治疗组不良反应的发生率明显低于对照组,两组差异具有统计学意义（χ2＝4．24,P＜0．05）。结论：齐拉西酮联合小剂量氯氮平治疗男性难治性精神分裂症与单用氯氮平治疗临床疗效相当,但安全性高,且能更好地改善患者的认知功能。