Inflammation in Patients with Schizophrenia: The Therapeutic Benefits of Risperidone Plus Add-On Dextromethorphan

Increasing evidence suggests that inflammation contributes to the etiology and progression of schizophrenia. Molecules that initiate inflammation, such as virus- and toxin-induced cytokines, are implicated in neuronal degeneration and schizophrenia-like behavior. Using therapeutic agents with anti-inflammatory or neurotrophic effects may be beneficial for treating schizophrenia. One hundred healthy controls and 95 Han Chinese patients with schizophrenia were tested in this double-blind study. Their PANSS scores, plasma interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) levels were measured before and after pharmacological treatment. Pretreatment, plasma levels of IL-1β and TNF-α were significantly higher in patients with schizophrenia than in controls, but plasma BDNF levels were significantly lower. Patients were treated with the atypical antipsychotic risperidone (Risp) only or with Risp+ dextromethorphan (DM). PANSS scores and plasma IL-1β levels significantly decreased, but plasma TNF-α and BDNF levels significantly increased after 11?weeks of Risp treatment. Patients in the Risp+ DM group showed a greater and earlier reduction of symptoms than did those in the Risp-only group. Moreover, Risp+ DM treatment attenuated Risp-induced plasma increases in TNF-α. Patients with schizophrenia had a high level of peripheral inflammation and a low level of peripheral BDNF. Long-term Risp treatment attenuated inflammation and potentiated the neurotrophic function but also produced a certain degree of toxicity. Risp+ DM was more beneficial and less toxic than Risp-only treatment.Clinical Trial Registration: Protocol Record: HR-93-50; Trial Registration number: NCT01189006; URL: http://www.clinicaltrials.gov.     

奥氮平与利培酮治疗精神分裂症患者认知功能的疗效比较

目的:比较奥氮平与利培酮治疗精神分裂症患者认知功能的疗效和安全性。方法:回顾性分析98例精神分裂症患者资料,按治疗方案的不同分为对照组(49)和观察组(49)。正在接受抗精神病药物治疗者,停药洗脱7 d后入组。对照组患者给予利培酮片起始剂量1 mg,口服,每日2次,1周内增加剂量至4~6 mg,每日2次,并维持连续用药6个月。观察组患者给予奥氮平片起始剂量5 mg,口服,每日2次,1周内增加剂量至15~20 mg,每日2次,并维持连续用药6个月。观察两组患者的临床疗效,治疗前后阳性与阴性症状量表(PANSS)评分、韦氏记忆量表(WMS)评分[总记忆商(MQ)评分)]、连线测验(TMT)评分(TMT-A连线时间、TMT-A错误数、TMT-B连线时间、TMT-B错误数评分)、威斯康星卡片分类测验(WCST)评分(完成分类数、持续应答数、总错误数、持续错误数及总正确数),并记录不良反应发生情况。结果:两组患者总有效率比较,差异无统计学意义(93.88%vs.97.96%,P>0.05)。治疗后,两组患者PANSS评分、TMT-A连线时间、TMT-A错误数、TMT-B连线时间、TMT-B错误数、持续应答数、总错误数及持续错误数评分均显著低于同组治疗前,且观察组PANSS评分显著低于对照组,其余指标组间比较差异无统计学意义(P>0.05);两组患者MQ评分、完成分类数、总正确数评分均显著高于同组治疗前,差异均有统计学意义(P<0.05或P<0.01),但组间比较差异无统计学意义(P>0.05)。观察组患者体质量增加、嗜睡发生率均显著高于对照组,锥体外系反应、失眠、头痛头晕、口干发生率均显著低于对照组,差异均有统计学意义(P<0.05)。结论:奥氮平与利培酮治疗精神分裂症的疗效相当,均可有效改善患者认知功能,而奥氮平在改善精神症状方面优于利培酮,但体质量增加、嗜睡发生率较高。     

齐拉西酮与利培酮对首发精神分裂症患者对照研究

目的:探讨齐拉西酮与利培酮治疗首发精神分裂症疗效及不良反应。方法:将100例首发精神分裂症患者随机分为齐拉西酮组和利培酮组各50例,分别于治疗前、治疗12周评定PANSS量表,评估不良反应发生率。结果:齐拉西酮组和利培酮组疗效相仿,差异无统计学意义(P0.05)。齐拉西酮组的不良反应显著少于利培酮组,差异有统计学意义(P0.05)。结论:齐拉西酮与利培酮疗效相当,但不良反应发生率较低,值得在临床推广应用。     

服用奥氮平、利培酮精神分裂症患者的心电图分析

目的：了解服用奥氮平、利培酮治疗精神分裂症患者心电图变化情况。方法随机对服用奥氮平160例,利培酮60例精神分裂症患者心电图进行分析。结果奥氮平组心电图表现正常65例（40.63％）,心电图异常95例（59.37％）。利培酮组心电图表现正常22例（36.67％）心电图异常38例（63.33％）,两药均可引起心电图改变。主要窦性心动过速,过缓,心律不齐,ST-T改变,T波异常,Q-T间期延长,短P-R间期,U波改变。二者无明显差异（P＞0.05）。随着用药时间和剂量的增加两药的心电图异常率亦增加。结论奥氮平与利培酮都会影响心电图改变,特别在药物增加和大剂量长期应用患者应复查心电图。     

Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia

Background:

Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics.

Methods:

To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes.

Results:

There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors’ efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis.

Conclusions:

Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups—plausibly due to differences in the mechanisms of action. Antidepressants may not worsen the course of psychosis. Better designed, larger, and longer randomized controlled trials are needed.     

Sex-Specific Association between Antioxidant Defense System and Therapeutic Response to Risperidone in Schizophrenia: A Prospective Longitudinal Study

Background: There are various differences in response to different antipsychotics and antioxidant defense systems (ADS) by sex. Previous studies have shown that several ADS enzymes are closely related to the treatment response of patients with antipsychotics-naïve first-episode (ANFE) schizophrenia.Objective: Therefore, the main goal of this study was to assess the sex difference in the relationship between changes in ADS enzyme activities and risperidone response.Methods: The plasma activities of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and total antioxidant status (TAS) were measured in 218 patients and 125 healthy controls. Patients were treated with risperidone for 3 months, and we measured PANSS for psychopathological symptoms and ADS biomarkers at baseline and at the end of 3 months of treatment. We compared sex-specific group differences between 50 non-responders and 168 responders at baseline and at the end of the three months of treatment.Results: We found that female patients responded better to risperidone treatment than male patients. At baseline and 3-month follow-up, there were no significant sex differences in TAS levels and three ADS enzyme activities. Interestingly, only in female patients, after 12 weeks of risperidone treatment, the GPx activity of responders was higher than that of non-responders.Conclusion:These results indicate that after treatment with risperidone, changes in GPx activity were associated with treatment response, suggesting that changes in GPx may be a predictor of response to risperidone treatment in female patients with ANFE schizophrenia.     

抗氧化药联合利培酮治疗精神分裂症的疗效研究

目的:探讨抗氧化药辅助治疗精神分裂症的疗效.方法:将80例精神分裂症患者随机双盲分为治疗组和对照组各40例,治疗组给予抗氧化药(维生素C 200 mg及维生素E 100 mg)联合利培酮,对照组安慰药合并利培酮;抗氧化药和安慰药用法相同,均tid,po.两组患者开始给利培酮1 mg&#8226;d 1,午饭后服用,渐增至3～6 mg&#8226;d 1,治疗组最高剂量(4.52±0.39) mg&#8226;d 1,对照组最高剂量(4.54±0.39) mg&#8226;d 1,两组用量差异无显著性(P＞0.05). 治疗12周进行比较.采用阳性和阴性症状量表(PANSS)评定疗效,用不良反应量表和锥体外系不良反应量表评定不良反应.结果:两组之间疗效差异无显著性(P＞0.05).在认知因子、阴性因子、PANSS总分减分率方面,治疗组优于对照组(P＞0.05).对照组出现锥体外系不良反应例数偏高.结论:抗氧化药辅助抗精神病药物治疗精神分裂症,在认知功能和阴性症状方面有效,并能减轻抗精神病药物不良反应.     

阿立哌唑与利培酮治疗精神分裂症的疗效比较

目的 考察阿立哌唑治疗精神分裂症的有效性及安全性. 方法 60例符合CCMD-3精神分裂症患者随机分为治疗组和对照组各30例.治疗组给予阿立哌唑,起始剂量5 mg·d^-1,以后每周增加5～10 mg,治疗剂量10～30 mg·d^-1;对照组给予利培酮,起始剂量1 mg·d^-1,隔3～7 d增加1 mg,2周内加至4 mg·d^-1,治疗剂量2～6 mg·d^-1,疗程均为8周.采用阳性症状与阴性症状量表及不良反应症状量表评定疗效与不良反应. 结果 治疗8周后,治疗组显效率63.3%,有效率90.0%,对照组显效率63.3%,有效率86.7%（P>0.05）.两组治疗后阳性症状与阴性症状评分均显著下降（P<0.01）, 治疗组不良反应发生率显著低于对照组（P<0.01）.结论 阿立哌唑与利培酮对精神分裂症疗效相当,前者所致不良反应发生率低,是一种安全有效的抗精神病药物.     

氯氮平和利培酮治疗精神分裂症的疗效比较

目的:比较氯氮平和利培酮治疗精神分裂症的疗效和不良反应.方法:符合CCMD 3诊断标准的精神分裂症患者80例,随机分为治疗组和对照组各40例,治疗组给予氯氮平,初始量25 mg&#8226;d 1,po,2周内递增至治疗量200～500 mg&#8226;d 1;对照组给予利培酮,初始量1 mg&#8226;d 1,po,2周内递增至治疗量2～8 mg&#8226;d 1.疗程均为8周.用BPRS评定疗效,用TESS评定不良反应.结果:治疗组和对照组的显效率分别为65.0%,42.5%(P＜0.05).治疗组的主要不良反应为过度镇静、流涎、心动过速及白细胞异常等;对照组的主要不良反应为EPS、失眠、激越及泌乳等.结论:氯氮平治疗精神分裂症起效快且疗效优于利培酮.     

利培酮和奥氮平在难治性精神分裂症患者治疗中的应用效果对比分析

目的分析对比难治性精神分裂症采用利培酮和奥氮平的临床治疗效果。方法选取我院2017年1月至2018年1月收治的难治性精神分裂症患者68例,采用奇偶法分为研究组和参照组,每组各34例,参照组给予奥氮平治疗,研究组患者给予利培酮治疗,比较2组临床不良反应发生情况、治疗前后阴性症状、阳性症状以及一般病理评分。结果研究组不良反应总发生率5.88%低于参照组26.46%,组间对比具有显著性差异(P <0.05);2组治疗前阴性症状、阳性症状以及一般病理评分对比无显著性差异(P> 0.05),治疗后研究组评分低于参照组,组间对比统计学意义存在(P <0.05)。结论治疗难治性精神分裂症采用利培酮治疗效果优于奥氮平治疗效果,可全面改善患者临床症状,并且不良反应发生率也相对较低,其临床用药安全性较高。     

利培酮与奥氮平对不同性别精神分裂症患者甲状腺激素水平的影响

目的 探讨利培酮和奥氮平对不同性别精神分裂症患者甲状腺激素水平的影响.HT5"H方法 将86例精神分裂症患者随机分成服用利培酮和奥氮平两组,其中利培酮组43例,使用剂量范围为1日4~6mg.奥氮平组43例,使用剂量范围为1日12.5~20mg.两组的年龄、男女性别比均无显著性差异(P>0.05),均为中国汉族人.两组患者均在用药前及用药4周末测定促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)及血清游离甲状腺素(FT4)水平.结果 利培酮及奥氮平组在治疗后均有FT3及FT4的下降,差异有统计学意义(P<0.05).两组对FT3及FT4的影响大小无显著差异(P>0.05).利培酮组及奥氮平组不同性别间甲状腺功能的变化无显著差异(P>0.05).结论 利培酮及奥氮平均会引起FT3及FT4等甲状腺功能指标的下降,与性别无明显关系.     

利培酮与齐拉西酮对精神分裂症患者糖脂代谢和细胞因子水平的影响研究

目的:观察利培酮与齐拉西酮对精神分裂症患者糖脂代谢和细胞因子水平的影响。方法:选择76例精神分裂症患者,随机均分为利培酮组和齐拉西酮组。利培酮组患者口服利培酮片,起始剂量为1 mg/d,1周内逐渐加量至4⁶ mg/d;齐拉西酮组患者口服齐拉西酮片,起始剂量为40 mg/d,分2次服用,1周内逐渐加量至1206 mg/d;齐拉西酮组患者口服齐拉西酮片,起始剂量为40 mg/d,分2次服用,1周内逐渐加量至120¹60 mg/d。两组患者均以2周为1个疗程,共治疗4个疗程。比较患者治疗前后血糖、胰岛素、血脂、瘦素(LEP)和细胞因子水平。结果:治疗后两组患者血糖、胰岛素、血脂、LEP水平均较治疗前显著升高,治疗前后比较差异大多有统计学意义(P<0.05),且齐拉西酮组患者空腹胰岛素(FINS)、胰岛素敏感指数(ISI)、LEP升高较利培酮组更显著,利培酮组患者总胆固醇(TC)升高较齐拉西酮组更显著,两组比较差异均有统计学意义(P<0.05);治疗后两组患者细胞因子水平均较治疗前显著降低,治疗前后比较差异均有统计学意义(P<0.05),且利培酮组患者细胞因子水平的改善均优于齐拉西酮组,两组比较差异均有统计学意义(P<0.05)。结论:利培酮与齐拉西酮均可能使精神分裂症患者超重、肥胖和糖尿病的发生率升高,利培酮对患者TC影响较大,齐拉西酮对患者FINS、ISI和LEP影响较大,同时两药可降低精神分裂症患者的细胞因子水平,利培酮对细胞因子水平的改善优于齐拉西酮。     

帕利哌酮缓释片治疗精神分裂症的疗效观察

摘 要 目的：观察帕利哌酮缓释片治疗精神分裂症的疗效和预后。方法: 精神分裂症患者72例按入院先后顺序分为观察组(n=35)和对照组(n=37)。观察组给予帕利哌酮缓释片治疗,对照组给予利培酮片治疗。两组均治疗8周。采用阳性和阴性症状量表(PANSS)评价两组患者的治疗效果,并比较两组患者社会功能缺陷量表(SDSS)及预后。 结果: 治疗后2周末开始,两组患者的PANSS总分、阳性症状评分、阴性症状评分以及一般病理症状评分均较治疗前明显降低(P<0.05),且观察组各项评分均明显低于同期对照组(P<0.05)。治疗后两组患者的SDSS评分均较治疗前明显降低(P<0.05),且观察组明显低于对照组(P<0.05)。观察组总有效率为94.3%,明显高于对照组的67.6%(P<0.05)。观察组焦虑、静坐不能等不良反应发生率和总药品不良反应发生率均明显低于对照组(P<0.05)。结论:帕利哌酮可有效缓解精神分裂症患者的病情,起效快、不良反应少,值得临床推广使用。     

齐拉西酮与利培酮治疗精神分裂症成本-效果分析

目的：评价齐拉西酮与利培酮治疗精神分裂症的经济学效果。方法：120例精神分裂症患者随机分为2组，分别服用齐拉西酮与利培酮，均连用6周，采用成本-效果分析法对2组进行分析。结果：齐拉西酮组和利培酮组显效率分别为86．67％和85．00％（P〉0．05），成本分别为602．13元和607．85元。结论：齐拉西酮治疗精神分裂症较经济。     

观察盆腔炎低频治疗仪+中药灌肠盆腔炎的临床效果

目的:探讨盆腔炎低频治疗仪+中药灌肠盆腔炎的临床疗效。方法:选取2010年11月~2012年12月在某院接受治疗的100例盆腔炎患者,随机分为两组,对照组采用中药灌肠和盆腔炎治疗仪治疗,观察组采用盆腔炎低频治疗仪+中药灌肠治疗,对比分析两组患者的临床疗效。结果:观察组患者的临床疗效显著高于对照组患者,P<0.05差异具有统计学意义。结论:对盆腔炎患者使用低频治疗仪+中药灌肠治疗疗效显著,具有临床价值意义,可以大力推广。     

Antioxidant Enzymes and Weight Gain in Drug-naive First-episode Schizophrenia Patients Treated with Risperidone for 12 Weeks: A Prospective Longitudinal Study

Background: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities.Objective: The activities of plasma superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls.Methods: Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities, and MDA levels were measured at baseline and during follow-up.Results: Compared with healthy controls, the patients showed higher activities of SOD and CAT but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with body weight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparing SOD, CAT, GPx activities and MDA levels between the WG group and the non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in the non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up.Conclusion: These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.     

奥氮平与利培酮对精神分裂症患者生活质量影响的对照研究

目的评价国产奥氮平与利培酮治疗精神分裂症的疗效、安全性及其对患者生活质量的影响。方法将78例首发精神分裂症患者随机分为奥氮平组和利培酮组,各39例,治疗8周,采用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)、生活质量综合评定问卷(GQOLI)分别评定患者的疗效及生活质量。结果两组PANSS总分治疗后均明显下降(P<0.01),组间差异则无显著性(P>0.05)。奥氮平组的显效率为66.67%、有效率为84.62%,利培酮组的显效率为61.54%、有效率为82.05%,两组比较无显著性差异(P>0.05)。两组GQOLI评分治疗8周末除物质生活维度无显著性变化外,其他各维度评分均显著性提高(P<0.05),而组间生活质量4个维度评分亦无显著性差异(P>0.05)。两组不良反应发生率低且程度轻,奥氮平组体重增加比例较高,而利培酮组锥体外系反应比例较高。结论奥氮平和利培酮对精神分裂症均有显著疗效,安全性高,能较好地提高患者的生活质量。     

阿立哌唑与利培酮治疗首发精神分裂症

目的比较阿立哌唑与利培酮治疗首发精神分裂症的疗效及不良反应。方法选择我院诊断为精神分裂症患者73例,随机进入阿立哌唑组或利培酮组接受治疗,分别在治疗0、2、4、8周,采用阳性与阴性症状量表(PANSS)和不良反应量表(TESS)评定其疗效和不良反应。结果阿立哌唑与利培酮疗效相当,阿立哌唑能迅速控制精神症状,产生不良反应小。结论阿立哌唑对首发精神分裂症治疗安全有效。     

利培酮治疗精神分裂症的药物副反应动态观察

目的观察单一使用利培酮治疗精神分裂症的药物反应,寻求预防及处理的方法。方法对36例符合CCMD-3精神分裂症诊断标准的患者,给予利培酮治疗8周,对人组患者出现的药物副反应在治疗前期,中期,后期采用药物副反应症状量表（TESS）进行评分。并记用药物剂量,分析药物使用时间与剂量大小所出现药物反应的关系。结果用药后出现药物副反应不少,以锥体系症状多见。第4周时单项症状中静坐不能占36．11％,震颤占19．44％,肌张力增高占16．67％。利培酮对睡眠障碍改善较差,可能也存在失眠的副反应,其余副反应较轻,特殊的副反应有排尿困难2例,泌乳2例等。结论药物反应的发生与药物剂量有一定关系,对症处理好副反应有利于提高患者治疗的依从性。