电休克治疗用于精神分裂症的激越症状:随机对照试验的meta分析（英文）

背景:躁动在精神分裂症治疗中是一个重大挑战。电休克疗法(ECT)对各种精神疾病是一种快速、有效、和安全的治疗,但ECT对精神分裂症的躁动治疗的相关meta分析还尚未报道。目标:系统地评估单一使用ECT或ECT合并使用其他抗精神病药物(APs)的对精神分裂症的躁动治疗的有效性和安全性。方法:进行随机对照试验(RCT)的系统文献搜索。两名独立评估者筛选研究、提取结果数据与现有数据的安全性、进行质量评估和数据合成。采用建议、评估、开发、和评价的工作组等级(GRADE)来判断主要成果的证据的总体水平。结果:一共确定了中国有七个RCTs,包括ECT单一使用(4个RCTs有5个治疗组,n=240)和ECT-APs合并使用(3个RCTs,n=240)。研究对象平均年龄34.3(4.5)岁,平均治疗时间为4.3(3.1)周。所有7个RCTs非盲法,并且根据Jadad量表7项RCTs均被评为低质量。样本的Meta分析发现与APs单一治疗相比,单一使用ECT或ECT-APs合并使用阳性和阴性症状量表(PANSS)的躁动子因子评分改善均无显著性差异(ECT单一使用:weighted mean difference(WMD)=-0.90,95%confidence interval(CI):(-2.91,1.11),p=0.38;ECT-APs合并使用:WMD=-1.34,(95%CI:-4.07,1.39),p=0.33)。然而,PANSS总分(WMD=-7.13,I~2=0%,p=0.004)和兴奋子因子评分(WMD=-1.97,p0.0001)、ECT治疗14天后的PANSS总分(WMD=-7.13,I~2=0%,p=0.004)和第7天和第14天的兴奋子因子评分(WMD=-1.97to-1.92,p=0.002 to 0.0001)均显示单一使用ECT优于APs单一治疗。ECT-APs合并治疗结束时(WMD=-10.40,p=0.03)和治疗后7天(WMD=-5.01,p=0.02)的PANSS总分显示均优于APs单药治疗。头痛(p=0.0001,number-needed-to-harm(NNH)=3,95%CI=2-4)是唯一的ECT单一治疗后不良反应,并且ECT单一治疗组比APs单药治疗发生的更频繁。根据GRADE方法,主要结果的证据水平被评为"非常低"(37.5%)和"低"(50%)。结论:基于中国7个RCTs合并的数据发现ECT单一治疗或ECT-APs合并治疗在精神分裂症患者的躁动治疗中并没有优势。然而,ECT单一治疗或ECT-APs合并治疗均与PANSS总分减低显著有关。需要高质量的RCTs验证目前的解释。     

抗精神病药物合并电抽搐治疗对难治性精神分裂症患者的疗效和安全性:一项系统综述和meta分析（英文）

背景:抗精神病药物合并电抽搐治疗(electroconvulsive therapy,ECT)对难治性精神分裂症患者的疗效和安全性还不确定。目的:对电抽搐治疗在难治性精神分裂症中的应用的相关中英文文献进行系统综述和meta分析。方法:在中英文数据库中检索2015年5月20日前发表的关于抗精神病药物合并ECT治疗难治性精神分裂症疗效和安全性的研究。由两名研究人员根据预先设定的标准独立筛选和评估文献。采用Review Manager5.1软件进行数据分析。结果:共纳入22项随机对照研究,其中在中国大陆开展的研究有18项。本研究对22项研究中的18项研究共1394例样本进行meta分析后发现,相比于单独使用抗精神病药物,抗精神病药物合并ECT治疗达到各研究特定的"临床改善"标准的比例要显著高(RR=1.31,95%CI=1.22-1.41)。根据推荐GTADE分级的评估、制定和评价标准(Grades of Recommendation,Assessment,Development,and Evaluation,GRADE),该疗效评估的证据质量是"中等"。但是,在治疗过程中出现头痛的参与者比例在合并治疗组中显著更高(RR=9.10,95%CI=3.97-20.86,基于8项研究517例样本)。合并治疗组中出现记忆受损的患者的比例也高(RR=6.48,95%CI=3.54-11.87,基于7项研究577例样本)。这些不良反应的证据质量被评定为"非常低"。结论:有关抗精神病药物合并ECT治疗难治性精神分裂症的高质量随机对照临床试验很少。该meta分析发现,抗精神病药物合并ECT可以改善难治性精神分裂症患者的精神症状,但大多数研究提供的方法学信息不全,存在发表偏倚(更偏向于合并治疗组结果相对好的研究),有关不良反应、认知受损和整体功能的证据质量较低,这使我们需要对结果的效度有所质疑。     

褪黑素治疗精神分裂症患者迟发性运动障碍的meta分析

目的:此荟萃分析基于随机对照试验(RCTs)文献系统评估褪黑素对精神分裂症患者迟发性运动障碍的临床疗效和安全性.方法:两位独立评估者从以下数据库对相关的临床随机对照试验(RCT)文献进行检索(万方数据、中国知网(CNKI)、中国生物医学文摘数据库和PubMed、PsycINFO、Embase、Cochrane Library数据库),检索时间截止于2017年6月8日.以TD症状严重程度为主要结局指标,采用Rev Man 5.3版本进行统计分析,对RCTs的质量评估采用Cochrane风险评估偏倚和Jadad量表来评估各种偏倚的风险性.采用GRADE(Grades of Recommendation,Assessment,Development,and Evaluation)系统推荐分级方法对meta-分析结果的整体证据质量水平进行分级评价.结果:最终筛选确定4个RCTs(n=130).3个RCTs采用双盲法,1个RCT单盲,根据Cochrane风险评估偏倚和Jadad量表显示3个RCTs的疗效评估指标的证据质量被评定为"高质量".与对照组相比,根据不自主运动量表(AIMS)评定褪黑素可改善TD严重程度(4个RCTs,n=130,加权平均差值(WMD):-1.52(95%CI:-3.24,0.20),p=0.08;I2=0%),但尚没有达到显著差异.根据等级方法,改善TD症状的meta分析结果的整体证据质量被评为"低",而关于不良反应和认知损害方面则数据太少.结论:荟萃分析表明,褪黑素或可改善精神分裂症TD症状.但仍有待今后更高质量和更大样本的RCTs验证.     

精神分裂症患者住院时间与疗效的关系

目的:探讨精神分裂症患者住院时间与疗效的关系。方法:以10 d为间隔将235例精神分裂症患者按住院时间分为7~20 d、30 d、40 d、50 d、60 d及60 d组,在住院第1周和最后1周分别应用阳性和阴性症状量表(PANSS)及自知力和治疗态度问卷(ITAQ)评估病情及自知力;分析住院时间与疗效的关系。结果:235例患者平均住院时间为64.3 d;住院时间与出院时ITAQ总分(r=0.294)、PANSS总分(r=-0.407)、阳性症状分(r=-0.369)及PANSS总分减分率(r=0.377)、阳性症状分减分率(r=-0.369)的相关系数在7~30 d组最大;住院≥31 d后其疗效与30 d比较差异无统计学意义。结论:精神分裂症患者住院30 d后,疗效可能不会随着住院时间延长而显著改善。     

非典型抗精神病药合并丁螺环酮治疗精神分裂症患者的对照研究

目的:探讨非典型抗精神病药(AAPDs)合并丁螺环酮对精神分裂症患者的治疗作用。方法:将85例精神分裂症患者分为研究组(43例)和对照组(42例),两组在单一AAPD常规治疗基础上,研究组及对照组分别加用丁螺环酮及安慰剂,疗程12周。治疗前及治疗4、8、12周后分别给予阳性及阴性症状量表(PANSS)、韦氏成人智力量表(WAIS-R)、韦氏记忆量表(WMS)评分;治疗4、8、12周后给予治疗中出现的症状量表(TESS)评定;以PANSS减分率评价疗效。结果:治疗第8周起两组PANSS总分均较治疗前明显降低(P0.05或P0.01);12周末研究组PANSS总分显著低于对照组(P0.01);总有效率(88.4%)显著高于对照组(71.4%)(P0.05);治疗8周后两组WAIS-R总分、言语量表分、操作量表分及WMS分较治疗前明显增高,研究组改善更明显(P均O.05)。结论:AAPDs合并丁螺环酮较单一AAPDs治疗精神分裂症可获得更好的疗效和认知功能改善,且无增加不良反应。     

太极拳治疗精神分裂症:系统综述（英文）

背景:太极拳起源于中国,是一种适度的有氧运动,可促进身心的平衡和康复。这一运动已用作精神分裂症患者的辅助治疗。然而,还没有关于太极拳辅助治疗精神分裂症患者的meta分析或系统综述的报告。目的:用随机对照试验(RCT)的数据进行系统综述和meta分析来检验太极拳辅助治疗精神分裂症患者的疗效。方法:两位评估者各自系统地检索中英文数据库中用太极拳治疗精神分裂症患者的RCT研究,并进行研究项目的选择、数据提取、质量评估和数据合并。采用Review Manager(版本5.3)进行统计分析。采用推荐分级的评估、制定与评价(Cochrane Grades of Recommendation,Assessment,Development,and Evaluation,GRADE)来评估证据的强度。结果:在中国大陆和香港进行的6项RCTS研究中,共有483名参与者,其中干预组215例,对照组268例。试验平均持续16.0(6.2)周。我们发现在研究期间,干预组阴性症状改善情况与对照组相比有显著差异[5项试验,6个治疗组,n=451,SMD:-0.87(95%CI:-1.51,-0.24),p=0.007;I2=90%],其中2项研究用阳性和阴性症状量表(PANSS)中的阴性症状分量表评估,另外3项用阴性症状评定量表(SANS)评估。此外,研究期间研究组与对照组间阳性症状的改善没有显著性差异[4项试验,5个治疗组,n=391,SMD:-0.09(95%CI:-0.44,0.26),p=0.60;I2=65%],其中2项研究用PANSS阳性症状分量表评估,2项用阳性症状评定量表(SAPS)。所有纳入的RCT研究均未报告不良反应。根据GRADE评估,主要结局指标的证据强度"很低"。结论:抗精神病药辅以太极拳治疗精神分裂症患者的疗效的数据尚不足,难于得出该疗效如何的明确结论。此外,纳入研究的随访时间相对较短,所有的研究评估结局指标时都没有使用盲法。需要有高质量的随机试验才能做出临床建议。     

褪黑素治疗精神分裂症患者迟发性运动障碍的meta分析（英文）

背景:迟发性运动障碍(TD)的临床特征是异常不自主运动。TD具有严重的不可逆的致残性和社会功能损害。目的 :此荟萃分析基于随机对照试验(RCTs)文献系统评估褪黑素对精神分裂症患者迟发性运动障碍的临床疗效和安全性。方法 :两位独立评估者从以下数据库对相关的临床随机对照试验(RCT)文献进行检索(万方数据、中国知网(CNKI)、中国生物医学文摘数据库和PubM ed、PsycI NFO、Embase、Cochrane Library数据库),检索时间截止于2017年6月8日。以TD症状严重程度为主要结局指标,采用Rev Man 5.3版本进行统计分析,对RCTs的质量评估采用Cochrane风险评估偏倚和Jadad量表来评估各种偏倚的风险性。采用GRADE(Grades of Recommendation,Assessment,Development,and Evaluation)系统推荐分级方法对meta-分析结果的整体证据质量水平进行分级评价。结果 :最终筛选确定4个RCTs(n=130)。3个RCTs采用双盲法,1个RCT单盲,根据Cochrane风险评估偏倚和Jadad量表显示3个RCTs的疗效评估指标的证据质量被评定为"高质量"。与对照组相比,根据不自主运动量表(AIMS)评定褪黑素可改善TD严重程度(4个RCTs,n=130,加权平均差值(WMD):-1.52(95%CI:-3.24,0.20),p=0.08;I2=0%),但尚没有达到显著差异。根据等级方法,改善TD症状的meta分析结果的整体证据质量被评为"低",而关于不良反应和认知损害方面则数据太少。结论 :荟萃分析表明,褪黑素或可改善精神分裂症TD症状。但仍有待今后更高质量和更大样本的RCTs验证。     

阿立哌唑与小剂量氯氮平治疗难治性精神分裂症对照研究

目的探讨阿立哌唑合并小剂量氯氮平治疗难治性精神分裂症的疗效和安全性。方法将40例难治性精神分裂症患者随机分为A组(阿立哌唑合并小剂量氯氮平,n=20)和B组(单用氯氮平,n=20)。于治疗前和治疗第4、8、12周末采用阳性与阴性症状量表(PANSS)评定临床疗效;使用副反应量表(TESS)评定不良反应,并进行对比分析。结果 2组治疗后PANSS总分较治疗前明显降低,A组显著低于B组,差异有统计学意义。2组治疗12周末有效率分别是80%、50%,差异有统计学意义(χ2=3.95,P<0.05)。2组不良反应比较差异有统计学意义(P<0.05)。结论阿立哌唑合并小剂量氯氮平治疗难治性精神分裂症疗效好,不良反应少且依从性好。     

帕罗西汀对精神分裂症阴性症状的疗效及对氯氮平血浓度影响的研究

目的 观察帕罗西汀对精神分裂症阴性症状的疗效及对氯氮平血浓度的影响.方法 对40例原服用氯氮平治疗且以阴性症状为主的精神分裂症患者合并帕罗西汀20mg/日治疗12周,分别于合并治疗前及治疗后4周、8周、12周评定阳性症状与阴性症状量表(PANSS)、副反应量表(TESS)及测定氯氮平血浓度.结果 合并帕罗西汀治疗4周、8周、12周末PANSS总分和TESS评分与合并前比较无显著差异(P＞0.05);女性患者合并帕罗西汀治疗4周、8周后氯氮平血浓度明显升高(p＜0.05),但治疗12周后与合并前比较无显著差异,男性患者则氯氮平血浓度无变化.结论 帕罗西汀对精神分裂症阴性症状无明显疗效,使得女性患者氯氮平血浓度有一段时间的升高,对男性患者无影响,合并用药后不良反应也不明显.     

精神分裂症患者多巴胺D2受体和多巴胺转运体基因表达水平与临床症状的关系

目的 探讨精神分裂症患者外周血淋巴细胞多巴胺D2受体(DRD2)和多巴胺转运体(DAT)的mRNA表达水平与精神分裂症临床症状的关系.方法 以实时荧光定量逆转录-聚合酶链反应技术检测治疗前精神分裂症组(25例)、长期服药(氯氮平)慢性精神分裂症组(27例)和对照组(30名)外周血淋巴细胞中DRD2和DAT的mRNA表达水平,同时对精神分裂症患者的阳性和阴性症状量表(PANSS)进行评定,并采用Spearman分析二者的相关性.结果 治疗前精神分裂症组、长期服药慢性精神分裂症组、对照组样本外周血淋巴细胞DRD2的基因表达水平分别为0.32±0.13、0.37±0.19、0.34±0.09,3组比较差异无统计学意义(F=0.510,P＞0.05)；DAT的基因表达水平分别为0.48±0.24、0.58±0.21、0.39±0.24,3组比较差异有统计学意义(F=4.330,P＜0.05)；长期服药慢性精神分裂症组DAT基因表达水平显著高于对照组(MS组内=0.194,P ＜0.01)；治疗前精神分裂症组DRD2基因表达水平与PANSS阳性症状分呈显著正相关(r=0.443,P＜0.05),DAT基因表达水平与PANSS总分(r=-0.418,P=0.075)、一般病理症状分(r=-0.434,P=0.063)的相关性未达统计学意义.结论 精神分裂症患者外周血淋巴细胞DRD2的基因表达水平与PANSS量表的阳性症状分显著正相关,而精神分裂症患者外周血淋巴细胞DAT的基因表达水平可能受氯氮平影响上调.     

太极拳治疗精神分裂症：系统综述

背景：太极拳起源于中国,是一种适度的有氧运动,可促进身心的平衡和康复。这一运动已用作精神分裂症患者的辅助治疗。然而,还没有关于太极拳辅助治疗精神分裂症患者的meta分析或系统综述的报告。目的：用随机对照试验（RCT）的数据进行系统综述和meta分析来检验太极拳辅助治疗精神分裂症患者的疗效。
　　方法：两位评估者各自系统地检索中英文数据库中用太极拳治疗精神分裂症患者的RCT研究,并进行研究项目的选择、数据提取、质量评估和数据合并。采用Review Manager（版本5.3）进行统计分析。采用推荐分级的评估、制定与评价（Cochrane Grades of Recommendation, Assessment, Development, and Evaluaiton,GRADE）来评估证据的强度。
　　结果：在中国大陆和香港进行的6项RCTS研究中,共有483名参与者,其中干预组215例,对照组268例。试验平均持续16.0（6.2）周。我们发现在研究期间,干预组阴性症状改善情况与对照组相比有显著差异[5项试验,6个治疗组,n=451, SMD：-0.87(95%CI：-1.51,-0.24),p=0.007; I2=90%],其中2项研究用阳性和阴性症状量表（PANSS）中的阴性症状分量表评估,另外3项用阴性症状评定量表（SANS）评估。此外,研究期间研究组与对照组间阳性症状的改善没有显著性差异[4项试验,5个治疗组,n=391, SMD：-0.09(95%CI：-0.44,0.26),p=0.60; I2=65%],其中2项研究用PANSS阳性症状分量表评估,2项用阳性症状评定量表（SAPS）。所有纳入的RCT研究均未报告不良反应。根据GRADE评估,主要结局指标的证据强度“很低”。
　　结论：抗精神病药辅以太极拳治疗精神分裂症患者的疗效的数据尚不足,难于得出该疗效如何的明确结论。此外,纳入研究的随访时间相对较短,所有的研究评估结局指标时都没有使用盲法。需要有高质量的随机试验才能做出临床建议。     

Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial

RATIONALE: Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. OBJECTIVES: To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. METHODS: We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. RESULTS: Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047). CONCLUSIONS: Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.     

无抽搐电休克与传统电休克治疗精神分裂症急性兴奋临床观察

目的 观察无抽搐电休克(MECT)与传统电休克(ECT)治疗精神分裂症患者急性兴奋的疗效和安全性.方法 将急性精神分裂症兴奋患者71例随机分为MECT组(治疗组)和ECT组(对照组),共治疗5次,采用阳性和阴性症状量表(PANSS)中兴奋因子(PANSS-EC)的变化评定临床疗效,副反应量表(TESS)评定不良反应,治疗前及治疗后分别评定血、尿、生化常规及心电图、血清CPK.结果 MECT组的PASS-EC总分明显降低,PASS-EC减分率(71±27)%,临床总有效率52.7%;ECT组PANSS-EC减分率(67±24)%,临床总有效率45.7%,2组间差异均无统计学意义(P均＞0.05).MECT组总的不良反应发生率41.7%,ECT组为54.3%,2组差异无统计学意义(P＞0.05).ECT组的头晕、头痛、肌肉酸痛发生率明显高于MECT组,差异有统计学意义(P＜0.05或＜0.01).结论 MECT治疗精神分裂症急性兴奋疗效肯定,安全性高.     

系统家庭治疗对精神分裂症患者生活质量的影响

目的:评估精神分裂症患者系统家庭治疗的临床疗效及对生活质量的影响。方法:将100例精神分裂症患者随机分成两组,各50例,联合治疗组使用抗精神病药物治疗合并系统家庭治疗,单纯药物组仅使用抗精神病药物治疗,疗程24个月。分别采用阳性与阴性症状量表(PANSS)、生活质量综合评定问卷(GQOLI)评估临床疗效和生活质量。结果:联合治疗组治疗后PANSS评分显著降低,GQOLI评分总分、心理健康维度分显著升高。单纯药物组量表分无显著改变。结论:系统家庭治疗能够减轻精神分裂症患者的精神症状和改善其生活质量。     

Short-term effect of ECT in middle-aged and elderly patients with intractable catatonic schizophrenia

BACKGROUND AND OBJECTIVE: The management of middle-aged and elderly patients with catatonic schizophrenia has long been a major problem in clinical geriatric psychiatry. Most cases are intractable because of medication resistance, medication intolerance, or severe medical conditions. Electroconvulsive therapy (ECT) is recognized as one of the most efficacious therapies for catatonic schizophrenia. Thus, we conducted a prospective study of the short-term effect of acute ECT on middle-aged and elderly patients with intractable catatonic schizophrenia. MATERIALS AND METHODS: Subjects were nine consecutive patients older than 45 years who had fulfilled the DSM-IV criteria for catatonic-type schizophrenia and had been referred for first-time acute ECT after other treatments had failed. The patients were treated at Tohoku University Hospital between January 1998 and March 2002. We evaluated the clinical response of these patients to acute ECT by means of the brief psychiatric rating scale (BPRS). We also evaluated adverse effects of acute ECT. RESULTS: The response rate was 100%. The total BPRS score was improved in all nine subjects at the end of the ECT course and 1 week after the final session in comparison with the total pre-ECT BPRS score (11.9 +/- 7.5 and 9.3 +/- 9.2 versus 57.1 +/- 13.1, respectively, p = 0.008, p = 0.008). The total Global Assessment of Functioning score was also improved significantly (from 10.8 +/- 9.4 just before ECT to 61.6 +/- 18.9 1 week after ECT, p = 0.008). Guy's five factors (thought disturbance, activation, anxiety-depression, hostility-suspiciousness, and anergia) improved significantly (p = 0.008, p = 0.008, p = 0.018, p = 0.012, p = 0.008, respectively). One patient showed supraventricular premature contractions (SVPCs) during an ECT seizure. After some ECT sessions, three patients exhibited mild to moderate delirium that disappeared within 3 days. However, no patient experienced a severe cognitive or physical adverse effect during the course of ECT. CONCLUSIONS: Acute ECT has a good short-term effect on middle-aged and elderly patients with intractable catatonic schizophrenia and appears to be safe. Our results indicate that systematic studies on a large scale are warranted for further investigation of the efficacy and safety of acute ECT for treating middle-aged and elderly patients with catatonic schizophrenia.     

Adjunctive Aspirin vs Placebo in Patients With Schizophrenia: Results of Two Randomized Controlled Trials

Two previous randomized controlled trials (RCTs) suggested that adjunctive aspirin is efficacious in treating schizophrenia. We conducted two 16-week double-blind randomized placebo-controlled RCTs of adjunctive 1000 mg aspirin vs placebo in schizophrenia. Study 1 included 200 patients, with Positive and Negative Syndrome Scale (PANSS) total score as the primary outcome. Study 2 included 160 patients with C-reactive protein (CRP) >1 mg/L at baseline; the primary outcome was PANSS-positive score. Dropout rates for aspirin/placebo were 12% in study 1 and 20% in study 2. Differences in outcome between aspirin and placebo were calculated with linear regression, adjusting for the baseline value of the outcome. No statistically significant between-group differences were found in primary or secondary outcomes in either study. Study 1: mean difference in PANSS at 16 weeks was −3.9 (95% CI: −8.4 to 0.5, P = .10, effect size (ES) = −0.25) and at 8 weeks was −3.5 (95% CI: −7.5 to 0.5, P = .11, ES = −0.22). Study 2: mean difference in PANSS at 16 weeks was 0.3 (95% CI: −4.1 to 4.7, P = .90, ES = 0.02) and in positive PANSS was 0.5 (95% CI: −1.0 to 2.1, P = .50, ES = 0.11). A meta-analysis of these data with the existing studies, excluding one with large baseline differences in total PANSS, found that the overall estimate of the effect of adjunctive aspirin on the PANSS total score comparing group means at the end of the study was −2.9 (95% CI: −6.6 to 0.7; P = .21), favoring aspirin. Our studies and meta-analysis failed to find a statistically significant improvement in the symptoms of schizophrenia from adjunctive aspirin therapy in comparison to placebo in schizophrenia. Trial registration: study 1: Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01320982","term_id":"NCT01320982"}}NCT01320982; study 2 (high CRP): EudraCT Number: 2014-000757-36.     

Association analysis of ZNF804A (zinc finger protein 804A) rs1344706 with therapeutic response to atypical antipsychotics in first-episode Chinese patients with schizophrenia

`The single-nucleotide polymorphism rs1344706 located in the ZNF804A zinc finger protein 804A gene is a well-established genome-wide significant variant for schizophrenia. The aim of this study was to investigate the potential association between this ZNF804A polymorphism and treatment response to atypical antipsychotic. Seventy-one first-episode inpatients with schizophrenia receiving olanzapine, aripiprazole, or quetiapine monotherapy were enrolled. Symptom response to treatment was assessed using the Positive and Negative Syndrome Scale (PANSS) on admission and reassessed after 4 weeks of treatment. Single-nucleotide polymorphism rs1344706 was genotyped by direct sequencing. There was substantial difference in treatment response among patients with 3 different genotypes regarding total PANSS score and positive subscore (for total PANSS score, F = 4.608, df = 2, P = .013; for positive subscore, F = 4.183, df = 2, P = .019). Compared with G homozygotes, T carriers showed significantly less improvement in total PANSS score as well as positive subscore (for total PANSS score, F = 8.724, df = 1, P = .004; for positive subscore, F = 9.392, df = 1, P = .005). Our results suggest that ZNF80A rs1344706 polymorphism may play a role in treatment response to atypical antipsychotic, although replication is required to confirm this finding.     

Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study

BACKGROUND: When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively. METHOD: The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale. RESULTS: Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005). CONCLUSION: Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.     

Ethnicity and treatment response in schizophrenia: a comparison of 3 ethnic groups

BACKGROUND: Numerous cultural and ethnic factors may directly and indirectly influence treatment outcome in schizophrenia. The present study compared the response to antipsychotic treatment in 3 ethnic groups of patients with schizophrenia. METHOD: Fifty black, 63 mixed descent, and 79 white patients with DSM-IV-diagnosed schizophrenia or schizophreniform disorder who were participants in multinational clinical drug trials were assessed by means of the Positive and Negative Syndrome Scale (PANSS). Treatment response was measured by the change in PANSS total scores and the change in positive, negative, and general psychopathology subscale scores from baseline to 6 weeks. Also, the percentage of responders (defined as > or = 40% reduction in PANSS total scores) was calculated for each group. RESULTS: Baseline PANSS scores differed significantly, being higher for black and mixed descent patients. Mixed descent patients showed the greatest mean +/- SD percentage reduction in PANSS total score (29.4 +/- 21.6) followed by black (28.4 +/- 14.7) and white (11.4 +/- 27.6) patients. Analysis of covariance revealed a significant effect of ethnicity on the reduction in PANSS total scores (p < .0001). The numbers of responders were 20 mixed descent (32%), 12 black (24%), and 7 white (9%) patients (p = .002). CONCLUSION: Significant ethnic differences in acute antipsychotic treatment response are demonstrated by this study. Factors such as diet, nutritional status, body mass, and substance use could be important, as well as genetically determined ethnospecific pharmacokinetic and pharmacodynamic differences. Delayed help-seeking may account for the higher baseline scores in the black and mixed descent patients.