Quetiapine in schizophrenia: onset of action within the first week of treatment

OBJECTIVE: Three placebo-controlled clinical trials have established the efficacy of the atypical antipsychotic quetiapine (Seroquel) in schizophrenia. These trials were designed and powered to detect a treatment difference in the primary endpoint at Week 6. The objective of the current analysis was to investigate the effect of quetiapine at earlier timepoints. RESEARCH DESIGN AND METHODS: A combined analysis of data from three acute, double-blind, placebo-controlled, randomised trials was carried out. The trials comprised hospitalised patients with an acute exacerbation of chronic or subchronic schizophrenia who were randomised to receive quetiapine 150-750 mg/day (n = 422) or placebo (n = 198). Symptoms were assessed using changes from baseline to Week 1 in the Brief Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score and the individual BPRS items of excitement, tension and depression. Changes from baseline to Weeks 1-6 were calculated for BPRS Factor 1 scores (which measures mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary scores. RESULTS: Within 1 week, overall symptom improvement (BPRS total score) was significantly (p < 0.05) greater with quetiapine than with placebo; improvement also occurred in individual BPRS items of excitement, tension and depression. Improvement in negative symptoms was significantly (p < 0.05) greater with quetiapine than with placebo from Week 1, as was the BPRS Factor I score from Week 2. More quetiapine- than placebo-treated patients showed a response of positive symptoms to treatment within 1 week (p < 0.05). CONCLUSIONS: The beneficial effects of quetiapine are observed within 1 week across a broad spectrum of symptoms.     

富马酸喹硫平对精神分裂症患者认知功能的影响

目的探讨富马酸喹硫平对精神分裂症患者认知功能的影响。方法本研究采用自身对照研究设计。对云南省精神病医院82例符合《中国精神障碍分类与诊断标准》的精神分裂症患者使用富马酸喹硫平治疗8周,于治疗前及治疗后使用阳性和阴性症状量表（Positive and Negative Syndrome Scale,PANSS）、韦氏记忆量表（Wechsler Memory Scale,WMS）和威斯康星卡片分类测验（Wisconsin CardSorting Test,WCST）进行评估,观察富马酸喹硫平对精神分裂症患者认知功能的影响。结果治疗8周后,PANSS总分显著降低（P〈0.01）;WCST中错误应答数、非持续性错误的分值显著降低（P〈0.05）;WMS中记忆商（memory quotient,MQ）、再生和理解的分值显著升高（P〈0.05）。结论富马酸喹硫平治疗精神分裂症可改善部分患者的认知功能。     

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.     

奎的平和氯丙嗪治疗精神分裂症的随机双盲对照研究

目的观测奎的平和氯丙嗪对精神分裂症患者的疗效及安全性。方法36例精神分裂症患者随机均分为奎的平组和氯丙嗪组,在治疗前、治疗后的第28、42天做PANSS量表、临床总体印象量表、锥体外系副反应量表、治疗中出现的不良反应量表,研究过程采用双盲双模拟法,所得数据用SPSS10.0进行统计分析。结果奎的平组和氯丙嗪组与治疗前比较均有显著差异(P<0.05),组间疗效无明显差异,但奎的平组的不良反应更轻。结论奎的平可作为治疗精神分裂症的一线药物。     

喹硫平治疗精神分裂症37例临床观察

目的 观察喹硫平治疗精神分裂症的疗效及安全性。方法 以喹硫平治疗精神分裂症病人37例，疗程6周。疗效评估采用阳性和阴性症状量表(PANSS)、简明精神病量表(BPRS)，不良反应评定采用副反应量表(TESS)。评定时间为治疗前及治疗后1～6周。结果痊愈54％(2067)，显效30％(11疙7)，进步13％(567)，无效3％(167)，BPRS总分、PANSS总分及各分量表分治疗前后比较差异均有显著意义。不良反应主要为治疗初期轻度镇静、体重增加。结论 喹硫平是一种安全有效的新型抗精神病药，能有效改善阳性症状和阴性症状，耐受性好。     

喹硫平与氯氮平治疗精神分裂症对照研究

目的：探讨国产喹硫平治疗精神分裂症的疗效和安全性。方法：将96例符合《中国精神障碍分类与诊断标准》第3版（CCMD-3）的精神分裂症患者随机分为两组,分别给予喹硫平（研究组,n=48）和氯氮平（对照组,n=48）治疗,疗程8周。分别于治疗前及治疗第2、4、6、8周末采用阳性和阴性症状量表（PANSS）和副反应量表（TESS）评定临床疗效和不良反应。结果：喹硫平组显效率70.8%,有效率91.7%。氯氮平组显效率72.9%,有效率93.7%。两组间显效率（X2=0.05,P〉0.05）有效率（X2=0.15,P〉0.05）的差异无统计学意义。两组间治疗后各时点PANSS总分、阳性症状、阴性症状以及一般病理症状各项分值均低于治疗前,而治疗后各时点组间差异无统计学意义（P〉0.05）。喹硫平组的嗜睡、便秘、头疼头晕、乏力、流涎的发生率分别为12.5%,4.17%,6.3%,4.2%和2.1%,明显低于氯氮平组（分别为45.8%,18.6%,20.8%,29.2%和39.6%）,两组差异均有统计学意义（X2=13.04,P〈0.01;X2=5.03,P〈0.05;X2=4.36,P〈0.05;X2=10.8,P〈0.01;X2=20.46,P〈0.05）结论：国产喹硫平治疗精神分裂症疗效确切,不良反应少,有利于患者对治疗的依从性,是一种安全有效的抗精神病药物。     

启维与氯丙嗪治疗精神分裂症的对照研究

目的评价启维与氯丙嗪治疗精神分裂症的临床疗效和安全性。方法将47例符合CCMD-3精神分裂症诊断标准的患者随机分为两组,分别给予启维与氯丙嗪治疗,于治疗前和治疗后6周末以BPRS、TESS量表评定其疗效和副反应。结果启维与氯丙嗪总体疗效相似,两组比较无显著差异(P>0.05)。而启维组的不良反应少于氯丙嗪组。结论启维是一种安全有效的新一代抗精神病药物,适合门诊精神分裂症病人使用。     

喹硫平治疗老年精神分裂症对照研究

目的：探讨喹硫平与奋乃静治疗老年精神分裂症的临床疗效和不良反应。方法：将60例老年精神分裂症患者随机分为两组,分别服用喹硫平和奋乃静,疗程8周。采用阳性与阴性症状量表（PANSS）评定疗效,副反应量表（TESS）及实验室检查评价不良反应。结果：喹硫平组显效率为66.7%,有效率为86.7%,奋乃静组显效率为56.7%,有效率为80%,两组差异无显著性;与治疗前相比喹硫平组阴性症状评分于治疗4周起显著降低（P〈0.05）,与奋乃静组比较有显著性差异（P〈0.05）。结论：喹硫平对老年精神分裂症疗效较好,尤其是阴性症状,且不良反应少。     

喹硫平与利培酮治疗精神分裂症的效果分析

目的 探讨喹硫平与利培酮治疗精神分裂症的效果.方法 选择82例患有精神分裂症的患者,随机分为对照组和治疗组,每组各41例,对照组患者给予利培酮治疗,治疗组患者给予喹硫平治疗.结果 治疗组患者的总有效率为90.2％,显著优于对照组的68.3％,差异有统计学意义（P＜0.05）;治疗组的精神分裂症状控制时间及接受治疗平均时间均明显少于对照组,差异有统计学意义（P＜0.05）;治疗组的不良反应发生率显著低于对照组,差异有统计学意义（P＜0.05）.结论 喹硫平治疗精神分裂症的效果良好,不良反应发生率低,值得临床推广应用.     

奎硫平与利培酮治疗精神分裂症的比较分析

目的：以利培酮为对照，探讨奎硫平治疗精神分裂症的疗效和不良反应。方法：将60例符合CCMD-3诊断标准的精神分裂症病人随机分为两组．分别用奎硫平和利培酮治疗8周，采用阳性症状和阴性症状量表（PANSS）评定临床疗效。用不良反应量表（TESS）评定不良反应。结果：两组治疗8周后的疗效差异无统计学意义（P〉0．05）；奎硫平组和利培酮组的显效率差异无统计学意义（P〉0．05）。结论：奎硫平和利培酮对精神分裂症的疗效相当，不良反应小。     

奎的平对精神分裂症患者生活质量的影响

目的观察奎的平对精神分裂症患者生活质量的影响。方法符合CCMD 3诊断标准的精神分裂症患者62例，分为两组。治疗组30例，均给予奎的平300～600 mg·d^-1，bid，PO;对照组32例，均给予氯氮平300～500 mg·d^-1，bid或tid，PO。两组均治疗6个月，观察两组精神分裂症患者的精神症状及生活质量的改变。结果两组患者精神分裂症阳性、阴性症状及PANSS总分的改善情况相似，差异无显著性（P＞0.05）。治疗6个月后，治疗组患者生活质量的改变，除精神支柱外，其他均非常明显地提高;对照组患者生活质量部分提高，但对患者的生理领域、心理领域、独立性领域没有明显改善。结论奎的平比氯氮平更能改善精神分裂症患者的生活质量。     

Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials

SUMMARY

Objective: To determine the effectiveness of quetiapine (Seroquel*) against specific aspects of schizophrenic symptomatology.

Research design and methods: Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine’s overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I–V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson–Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures.

Results: Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5?mg/day with a mean maximum dose of 686.0?mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness (?p < 0.001) and in 14 of the 18 individual BPRS items (?p < 0.001). Positive symptoms also improved (?p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400?mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (–10.0?µg/L) and placebo (–10.9?µg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively).

Conclusions: The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).     

奎的平与氯丙嗪治疗精神分裂症的对比研究

目的:探讨奎的平与氯丙嗪治疗精神分裂症的疗效及不良反应.方法:精神分裂症患者40例,随机分为治疗组和对照组各20例,分别给予奎的平与氯丙嗪治疗,奎的平及氯丙嗪初始剂量均为50 mg&#8226;d 1,隔日增加剂量50 mg,剂量范围300～500 mg&#8226;d 1,奎的平平均(433±19) mg&#8226;d 1,氯丙嗪平均(468±39) mg&#8226;d 1,疗程均为6周.采用阳性症状与阴性症状量表(PANSS)、不良反应症状量表(TESS)评定疗效及不良反应. 结果:治疗组显效率75.0%,有效率90.0%;对照组显效率50.0%,有效率90.0%.治疗组无明显锥体外系反应,对照组16例有锥体外系反应.结论:奎的平和氯丙嗪治疗精神分裂症均有确切疗效,奎的平对症状的改善更好.     

奎硫平与利培酮治疗精神分裂症的对照研究

目的探讨奎硫平治疗精神分裂症的效果与不良反应。方法将90例精神分裂症患者随机分为奎硫平治疗组和利培酮治疗组,各45例。于治疗前及治疗第1、2、4、8周末采用阳性与阴性症状量表（PANSS）评价临床疗效,副反应量表（TESS）评价不良反应。结果奎硫平组治疗有效率为75.6%高于利培酮组的73.3%,差异无统计学意义（P〉0.05）。奎硫平组锥体外系不良反应明显少于利培酮组（P〈0.05）,其他不良反应2组比较差异均无统计学意义（P〉0.05）。结论奎硫平治疗精神分裂症疗效肯定,不良反应少,依从性好。     

舒思与氟哌啶醇治疗精神分裂症疗效及依从性比较

目的 探讨评价舒思与氟哌啶醇治疗精神分裂症的疗效及依从性.方法 128例精神分裂症患者随机分为两组,分别给予舒思和氟哌啶醇治疗、均治疗18个月,于疗前,治疗后2个月、18个月采用阳性症状阴状量表(PANSS)、药物副反应量表(TESS)评价其疗效、副反应及依从性.结果 2个月后,舒思组有效率91.9%,氟哌啶醇组有效率89.8%,两组治疗前后比较有非常显著性的差异(P＜0.01),但两组间比较无显著性差异(P＞0.05);18个月后舒思有效率91.9%,氟哌啶醇组有效率69.4%.舒思组有非常显著性的疗效(P＜0.01),氟哌啶醇组有显著性疗效(P＜0.05),两组间比较具有显著性差异(P＜0.05).舒思组的不良反应发生率远低于氟哌啶醇组.结论 舒思与氟哌啶醇对精神分裂症患者均有较好的疗效,精神分裂症患者对舒思的依从性高主要是其疗效好和副反应轻.     

喹硫平与利培酮治疗精神分裂症对照研究

目的探讨喹硫平治疗精神分裂症的疗效及安全性。方法将110例精神分裂症患者随机分为两组各55例,研究组给予喹硫平治疗,对照组给予利培酮治疗,疗程8周。采用潘氏量表及付反应量表评定临床疗效和不良反应。结果研究组总有效率67．2％,对照组87．3％,两组比较有显著性差异（P〈0．05）。治疗2周末两组潘氏量表评分均较治疗前有显著性下降（P〈0．05）,4周末均有极显著下降（P〈0．01）,同期组间潘氏量表评分有显著或极显著性差异（P〈0．05或0．01）。两组不良反应评分无显著性差异（P〉0．05）但不良反应表现存有异同。结论喹硫平治疗精神分裂症疗效显著、安全,疗效虽然稍逊于利培酮,但对临床选药有一定的借鉴作用。     

Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action,a non-inferiority study*

ABSTRACT

Objective: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment¹. The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reuptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor).

Research design and methods: This was a randomized, double-blind, placebo- and active comparator-controlled study, in which patients (≥ 18 years) meeting DSM?IV criteria for Major Depressive Disorder (MDD) received duloxetine 60?mg once daily (QD; N = 273), escitalopram 10?mg QD (N = 274), or placebo (N = 137) for 8 weeks. The primary objective was to compare the onset of antidepressant efficacy, by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group.

Main outcome measures: Onset of efficacy was defined as a 20% decrease from baseline on the 17?item Hamilton Rating Scale for Depression (HAMD₁₇) Maier subscale that was maintained or exceeded at all subsequent visits.

Results: Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6% versus 35.2%, respectively (treatment difference = 7.4%; 95% confidence interval, –1.3% to 16.2%; p = 0.097). Both drugs showed significant improvement compared with placebo (?p ≤ 0.05) on the primary efficacy measure (Maier subscale) at Week 1 and endpoint (Week 8). No differences were found between duloxetine, escitalopram, and placebo rates of remission or response at 8 weeks. Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea, dry mouth, vomiting, yawning, and irritability. The rate of discontinuation due to adverse events did not differ significantly between treatment groups.

Limitations: Given the difficulties in constructing appropriate dose comparisons, the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole. This study employed a fixed-dose design; flexible-dose designs are more likely to find a difference between antidepressants and placebo.

Conclusion: In this study, both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8?week acute treatment period, while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks. Escitalopram at a starting dose of 10?mg QD was better tolerated than duloxetine at a starting dose of 60?mg QD. This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy, and the results show that duloxetine is at least as fast as (non-inferior to) escitalopram.

Trial registration: ClinicalTrials.gov identifier: NCT00073411.     

喹硫平对精神分裂症患者血脂代谢的影响

目的探讨喹硫平对精神分裂症患者血脂代谢的影响,并比较男女之间的差异。方法 2006年1月至2009年1月期间入院予喹硫平治疗的精神分裂症患者346例,分析喹硫平治疗8周前后的空腹血胆固醇(TC)、三酰甘油(TG)浓度变化。结果喹硫平治疗组TC及TG前后变化不明显,差异均无统计学意义(t=1.45),且男女患者之间无明显差异(t=1.03,P>0.05)。结论喹硫平对精神分裂症患者血脂代谢的影响不大,对于高血脂患者用药安全。     

温胆汤加减协同治疗精神分裂症的疗效

目的探讨分析温胆汤加减协同治疗精神分裂症的疗效及不良反应。方法将本院精神分裂症患者随机分为观察组与对照组。观察组采用温胆汤加减协同富马酸喹硫平片治疗,对照组单用富马酸喹硫平片治疗。结果观察组有效率为92％,对照组有效率为72％。两组治疗后第6周总分、阴性症状积分、阳性症状积分均较治疗前明显下降,观察组下降幅度高于对照组。观察组的药物不良反应发生率低于对照组。结论温胆汤加减协同治疗精神分裂症能够明显地减轻精神症状及降低精神药物的使用剂量。     

综合护理干预在首发精神分裂症患者中的应用研究

目的探讨综合护理干预应用于首发精神分裂症患者中的效果。方法将2009年2月-2012年4月来本院登记的100例首发精神分裂症患者随机分为干预组和对照组各45例,对照组给予常规的药物治疗并精神科基础护理;干预组应用综合护理干预,除药物治疗和精神科基础护理之外,还进行心理护理、健康教育、生活技能干预。护理干预4周后,采用SAS、SDS评分评价干预组和对照组患者的主观感受和抑郁程度。护理干预8周后,根据QOL-100评分标准,分别对两组患者进行生活质量评分。结果经过医护人员4周的治疗和护理之后,干预组SAS、SDS评分下降幅度明显高于对照组,两组差异有统计学意义（P〈0．05）。护理干预8周之后,干预组生活质量评分提高幅度明显高于对照组,两组差异有统计学意义（P〈0．05）。结论综合护理干预措施可以显著缓解精神分裂症患者焦虑、抑郁的负面情绪,有助于患者的康复;对首发精神分裂症患者积极采取综合护理干预措施。能显著改善临床疗效,有效提高患者生活质量。