奥氮平和喹硫平对慢性精神分裂症患者认知功能的疗效研究

目的了解奥氮平和喹硫平对慢性精神分裂症患者认知功能的改善情况,并比较二者对患者认知功能的改善程度是否具有差异性。方法87例经典抗精神病药物治疗疗效不显著或不能耐受不良反应的慢性精神分裂症患者随机分配替换为奥氮平及喹硫平治疗,分别在入组前、12周和6个月时进行精神症状的评定,包括PANSS、CGI、HAMD-17量表,以及认知功能的测定,包括言语学习、记忆、注意、执行功能、精神运动。结果78例患者完成12周的治疗（奥氮平=38,喹硫平=40）,65例临床稳定的患者（PANSS量表≤60分或PANSS减分率≥50％）完成6个月的治疗（奥氮平=32,喹硫平=33）。与基线比较,这些患者的精神症状在换药治疗6个月时均得到显著改善,认知功能在12周和6个月时也都得到显著改善。认知功能总体的改善在12周时最显著,6个月时的改善程度与12周时相当。具体分析单个认知功能的改善时发现12周时喹硫平组在言语流畅性、言语记忆、CPT反应时间方面较奥氮平组有显著性差异,而6个月时两者之间无显著差异。患者认知功能的改善和精神症状的改善之间的相关性较小。结论奥氮平和喹硫平均可改善慢性精神分裂症的认知功能,且两者改善的总体程度相当,但在具体的单个认知层面上稍有差异。     

奥氮平与利培酮对慢性精神分裂症认知功能的疗效

目的探讨奥氮平与利培酮在治疗慢性精神分裂症的认知功能的临床效果。方法选择本院2010—2012年收治的精神分裂患者98例,按随机数字法分为2组,分别给予奥氮平及利培酮治疗,分别在入组、治疗12周及6个月进行PAN-SS量表评定以及认知功能的测定。结果 A组42例和B组44例完成了6个月的治疗,所有患者从基线到6个月精神症状均显著改善,6个月时认知功能显著提高。结论奥氮平和利培酮均能显著改善慢性精神分裂患者的认知功能。     

奥氮平与氯氮平治疗精神分裂症临床对照观察

目的:探讨国产奥氮平治疗精神分裂症的临床疗效及其对生活质量的影响。方法:将64例精神分裂症患者随机分为奥氮平组和氯氮平组治疗8周,于治疗前后用阳性与阴性症状量表(PAN-SS)和治疗中出现的症状量表(TESS)评定其疗效和不良反应,生活质量量表(GQOLI-74)分析患者的生活质量。结果:奥氮平组与氯氮平组疗效差异无显著性(P>0.05);奥氮平组生活质量各维度改善均优于氯氮平组。结论:国产奥氮平和氯氮平对于精神分裂症的疗效相当,对提高精神分裂症患者的生活质量明显优于氯氮平。     

奥氮平与氯氮平治疗难治性精神分裂症对照研究

目的评价奥氮平治疗难治性精神分裂症的疗效及安全性。方法将64例难治性精神分裂症患者随机分为研究组和对照组,分别予以奥氮平和氯氮平治疗8周,采用PANSS量表和TESS量表评定疗效和不良反应。结果奥氮平组治疗前后PANSS减分率为39.3%,有效率为72.8%;氯氮平组治疗前后PANSS减分率为36.6%,有效率为59.4%。奥氮平组未见严重的不良反应。结论奥氮平与氯氮平治疗难治性精神分裂症均有良好疗效,奥氮平的副作用小,病人依从性好。     

奥氮平与氯氮平治疗精神分裂症的对照研究

目的：比较奥氮平与氯氮平治疗精神分裂症的疗效及改善社会功能的作用。方法：将70例精神分裂症患者随机分为奥氮平组或氯氮平组。治疗6个月后,采用阳性与阴性症状量表（PANSS）评定疗效,以治疗中出现的症状量表（TESS）评定不良反应,以社会功能缺陷量表（SDSS）评定社会功能。结果：两组患者治疗前后PANSS总分及各因子分比较差异均无显著性;奥氮平的过度镇静及抗胆碱能不良反应较少;治疗6个月后SDSS评定,在职业工作、婚姻职能、父母职能、社会性退缩、责任心和计划方面及总分,奥氮平组显著优于氯氮平组。结论：两组疗效相当,但奥氮平不良反应较少,对改善患者的社会功能明显优于氯氮平,有利于患者适应社会生活。     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较非经典抗精神病药奎硫平、奥氮平、氯氮平与经典抗精神病药氯丙嗪对精神分裂症患者认知功能的影响。方法：对160例住院精神分裂症患者随机开放分配接受奎硫平、奥氮平、氯氮平和氯丙嗪药物治疗。12周的急性期治疗后,获得临床稳定期的患者[阳性与阴性量表（PANSS）总分≤60或减分率／〉50％]进入固定剂量的24周治疗。分别在基线、治疗12周和24周进行威斯康星卡片分类测验（WCST）、言语流畅性测验、霍普金斯词语学习测验（HVLT-R）、持续操作功能测验（CPT）、韦克斯勒记忆测定（WMS）、韦克斯勒智能测定（WAIS）、连线试验测定、手指叩击试验测定。结果：奎硫平组、奥氮平组、氯氮平组治疗12周和24周后认知功能均有不同程度的改善（P均〈0．05）,明显优于氯丙嗪,而氯丙嗪组无显著改善。治疗12周后奎硫平组在改善执行功能、言语流畅性和警觉性显著优于奥氮平组和氯氮平组（P〈0．05）。奥氮平组在数字特征和连线测定上明显优于氯氮平组（P〈0．05）。3种非经典抗精神病药在认知功能总分的改善与PANSS总分、阴性症状分的改善有显著相关性（r=-0．32,P〈0．05）。结论：3种非经典抗精神病药奎硫平、奥氮平、氯氮平可不同程度改善精神分裂症患者的认知功能。     

奥氮平与氯氮平治疗巴金森病精神症状的对照

目的:对比奥氮平和氯氮平治疗巴金森病中精神症状的疗效与不良反应。方法:对27例奥氮平和25例氯氮平治疗的存在精神症状的巴金森病患者,在治疗的0、2、4、6周分别评定简明精神病评定量表(BPRS)、治疗中出现的症状量表(TESS)、锥体外系副反应量表(RSESE),对比两组间疗效与不良反应的差别。结果:2周时两组BPRS评分均较治疗前有显著性降低(P均<0.05)。两组间BPRS、RSESE评分在不同时间差异均无显著性(P均>0.05)。2、4、6周时奥氮平组的TESS评分明显低于氯氮平组,两组间差异有显著性(P<0.05)。结论:奥氮平和氯氮平对治疗巴金森病中精神症状的疗效相似,均未明显增加巴金森病的锥体外系反应。奥氮平的不良反应低于氯氮平。     

慢性精神分裂症患者应用氯氮平和喹硫平的疗效及认知功能变化

目的 观察氯氮平和喹硫平对慢性精神分裂症的治疗效果及治疗后患者认知功能的变化。方法 选取2010-02—2012-11在我院就诊的90例慢性精神分裂症患者,将经典抗精神病药物随机分配替换为氯氮平和喹硫平,分别对入组时和8个月末的精神症状及认知功能进行评估,用不良反应症状量表评定治疗16周后的不良反应。结果 88例临床稳定型慢性精神分裂症患者在经氯氮平或喹硫平治疗8个月后精神症状均明显好转,8个月后的认知功能也有显著改善,差异有统计学意义(P<0.05)。换药16周后喹硫平组患者出现活动减少、嗜睡、便秘、流涎、头晕及体质量增加等不良反应的发生率明显少于氯氮平组,差异有统计学意义(P<0.05)。结论 氯氮平和喹硫平对慢性精神分裂症均有显著治疗作用,且二者在认知功能的改善及疗效方面无显著差异,但与氯氮平相比,喹硫平的不良反应较少,是一种相对安全有效的抗精神病药物。     

奥氮平与氯丙嗪治疗精神分裂症对照研究

目的:比较奥氮平与氯丙嗪治疗精神分裂症伴阳性症状的疗效及不良反应。方法:对86例精神分裂症患者,随机分为奥氮平组(42例)和氯丙嗪组(44例)。疗程8周。采用简明精神病评定量表(BPRS)、阳性症状量表(SAPS)及副反应量表(TESS)评定疗效及安全性。结果:奥氮平和氯丙嗪治疗精神分裂症伴阳性症状的疗效相当,均无严重不良反应。奥氮平对焦虑抑郁、缺乏活力、激越冲动及行为障碍的疗效优于氯丙嗪。结论:奥氮平是一种安全有效的抗精神病药,特别是在改善认知功能和阳性症状方面疗效较好。     

奥氮平与氯氮平对患者生活质量的影响

目的：观察奥氮平、氯氮平对精神分裂症患者生活质量的影响。方法：对精神分裂症患者以奥氮平或氯氮平治疗，疗程6个月。用阳性症状与阴性症状量表(PANSS)评定疗效，用生活质量综合评定问卷(GQOLI)分析生活质量。结果：奥氮平组的躯体健康、心理健康及社会功能维度得分明显高于氯氮平组，均有显著差异。结论：奥氮平治疗精神分裂症患者，生活质量优于氯氮平。     

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.     

COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia

Preliminary evidence suggests that a single nucleotide polymorphism (SNP), the val108/158met SNP, within the gene that codes for catechol-O-methyltransferase (COMT), a key enzyme involved in regulating dopamine (DA) transmission within the prefrontal cortex (PFC), is related to cognitive function in schizophrenia and cognitive improvement with atypical antipsychotic drugs (APDs). Specifically, several studies have identified an association between working memory and executive functions, and COMT val108/158met genotype in schizophrenia; although there have been several negative findings that are likely related to small sample sizes and, possibly, medication status of patients at the time of testing. The association between COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine was investigated in a relatively large prospective sample of patients with schizophrenia, most of whom were unmedicated at baseline. Patients were genotyped for the COMT val108/158met SNP after completing a cognitive battery consisting of tests of attention, working memory, verbal learning and memory, executive function, and verbal fluency at baseline and after 6 weeks and 6 months of treatment with clozapine. Consistent with several previous studies, an association between COMT genotype and tests of executive function and working memory was identified at baseline. In addition, a novel interaction between genotype and improvement on tests of attention and verbal fluency was identified. Specifically, met homozygous and val/met heterozygous patients demonstrated significantly greater improvement than val homozygous patients following 6 months of treatment with clozapine. The results are discussed in relation to previous cross-sectional studies and prospective investigations of the associations between COMT genotype, cognition, and cognitive improvement with atypical APDs in schizophrenia.     

Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study

This study aimed to determine the effect of olanzapine and other antipsychotic drugs on cognitive functions after 6months of treatment. Baseline, 3month and 6month psychopathological and cognitive evaluations were made. Thirty-eight partially responsive outpatients with DSM-IV chronic schizophrenia diagnosis were included in the study. On the indication of their attending psychiatrists, 21 patients initiated treatment with olanzapine, and 17 remained on their previous treatment with other antipsychotic drugs. Cognitive assessments were blind to medication and psychopathological status.The olanzapine group presented a significantly greater improvement in negative symptomatology and verbal memory than the comparison group in repeated-measures of MANOVAs between baseline, 3month and 6month assessments. These differences remained statistically significant after covarying out gender, treatment with other atypical antipsychotics, biperidene doses and changes in positive and negative symptoms. In order to match previous differences between groups, cognitive baseline scores for each test were introduced as covariates, resulting in a significant improvement for the olanzapine group in negative symptomatology and the interference task of the Stroop test.We then re-analyzed the data, dividing the comparison group into two groups: risperidone-treated patients (n=9) and patients receiving conventional antipsychotic drugs (n=8). Post-hoc analyses between groups were carried out with baseline cognitive assessment as covariate. The olanzapine group improved significantly more than the risperidone group in negative symptomatology and in the interference task of Stroop test. The improvement in the number of categories of the Wisconsin Card Sorting Test was higher in risperidone patients than in those receiving olanzapine or conventional antipsychotic treatment. Conventional antipsychotic drugs did not present a significant improvement over atypical antipsychotic drugs in any cognitive function.In summary, in patients suffering from chronic schizophrenia, atypical antipsychotic agents were associated with slight differential improvements over time in attentional, verbal memory and executive functions compared with conventional neuroleptic drugs. No differential improvements were found in social functioning, verbal fluency, non-verbal domains of memory or visuo-motor abilities.     

Cognitive effects of atypical antipsychotic drugs in first-episode drug-nave schizophrenic patients

Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-nave patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.     

Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder

OBJECTIVE: To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder. METHOD: One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point. RESULTS: Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint. CONCLUSIONS: Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.     

Neurocognitive effects of clozapine,olanzapine, risperidone,and haloperidol in patients with chronic schizophrenia or schizoaffective disorder

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.     

Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia

OBJECTIVE: To assess changes in cognitive function in stable outpatients with schizophrenia switched to ziprasidone from conventional antipsychotics (n = 108), olanzapine (n = 104), or risperidone (n = 58) because of suboptimal efficacy or poor tolerability. METHODS: In three separate 6-week trials, patients received ziprasidone 40 mg b.i.d. for 2 days, followed by 20-80 mg b.i.d. for the next 40 days. Before switching, and at endpoint, patients were evaluated with tests of working and secondary verbal memory, vigilance, visuomotor speed, verbal fluency, and executive functioning. Principal components factor analysis was performed to test for clustering of cognitive variables. RESULTS: Significant improvements were seen at endpoint in secondary verbal memory (in all three groups), vigilance (in patients switched from conventional antipsychotics or risperidone), executive function (in patients switched from conventional antipsychotics or risperidone), and verbal fluency. Factor analysis on baseline scores suggested reduction of the cognitive variables to three factors: verbal skills, attention and short-term memory, and executive functioning. Analysis of z-transformed mean change in factor scores showed significant improvement in verbal skills and global score following the switch from conventional antipsychotics, olanzapine, or risperidone. CONCLUSIONS: Patients requiring a change in antipsychotic therapy may exhibit cognitive improvement following a switch to ziprasidone.     

A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia

Clozapine has been reported to improve selected aspects of cognitive function in neuroleptic-resistant schizophrenia. In this study, we report the first direct comparison of the effect of clozapine and typical neuroleptic drugs on cognitive function in neuroleptic-responsive schizophrenia. Sixty-four patients with recent onset, neuroleptic-responsive schizophrenia or schizoaffective disorder were randomly assigned to either clozapine (n = 35) or typical neuroleptics (n = 29) and followed for 12 months. They were administered a comprehensive cognitive test battery at baseline and at 6 weeks, 6 months and 12 months after initiating drug treatment. Treatment with clozapine improved psychomotor speed and attention [Digit Symbol Substitution Test (DSST)] and verbal fluency [Category Instance Generation and Controlled Word Association Test (CWAT)] at 6 weeks. The improvement in these measures was maintained throughout the 12-month period. Treatment with typical neuroleptics produced no sustained improvement in any cognitive measure, except for a tendency to improve delayed recall memory (Verbal List Learning Test). The improvement in the DSST and CWAT was significantly greater with clozapine treatment compared to that with typical neuroleptics. These improvements were not related to improvement in psychopathology. These results suggest that clozapine is superior to typical neuroleptics in improving specific types of cognitive function in recent onset, neuroleptic-responsive schizophrenia.     

One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy. It was hypothesized that olanzapine treatment would improve neurocognitive deficits to a greater degree than either risperidone or haloperidol treatment. This was a double-blind, randomized, controlled, parallel study with neurocognition assessed at baseline, and 8, 24, and 52 weeks. Per protocol, the haloperidol arm was discontinued. Four hundred and fourteen inpatients or outpatients with schizophrenia and schizoaffective disorder were treated with oral olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Individual domains (executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability) were transformed into composite scores and compared between treatment groups. At the 52-week endpoint, neurocognition significantly improved in each group (p < 0.01 for olanzapine and risperidone, p = 0.04 for haloperidol), with no significant differences between groups. Olanzapine- and risperidone-treated patients significantly (p < 0.05) improved on domains of executive function, learning/memory, processing speed, attention/vigilance, verbal working memory, and motor functions. Additionally, risperidone-treated patients improved on domains of visuospatial memory. Haloperidol-treated patients improved only on domains of learning/memory. However, patients able to remain in treatment for the entire 52 weeks benefited more from olanzapine or risperidone treatment than haloperidol treatment.