Developments in the pharmacological treatment of schizophrenia

Schizophrenia is, at once, a biological disease, a neuropsychological disorder and a dysfunction of social interactions. This presents clinicians with a series of problems with regards to therapy. In the first section of this article, some of the clinical challenges that face those attempting to develop new drugs, are summarised. Several potential pharmacological therapeutic targets that have been, and are continuing to be used, in the development of new antipsychotic drugs, are then considered. This is followed by an outline of the pharmacological and clinical profiles of some of the newer generation antipsychotics, as well as investigational drugs in the pipeline for schizophrenia. Finally, the implications of the introduction of these new drugs for the management of schizophrenia, are discussed.     

Some dopaminergic genes polymorphisms are not associated with response to antipsychotic drugs in schizophrenic patients

BackgroundTherapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients.MethodsOne hundred ninety one Caucasian patients admitted with exacerbation of paranoid schizophrenia were genotyped for polymorphisms of the DRD2 [the ins/del -141C (rs1799732) and exon 8 (rs 71653615)], DRD2/ANKK1 Taq IA (rs 1800497), DAT1 (the 40 bp VNTR), COMT (rs 4680), and MAOA gene (the 30 bp VNTR in promoter). The patients were randomly assigned to the treatment with perazine, olanzapine or ziprasidone givenasmonotherapy for 3 months. Treatment efficacy was measured from baseline (T0) to T1 (14 days) and T2 (3 months). A retention rate was also assessed at T1 and T2.ResultsThe three antipsychotics did not differ in terms of reduction of the PANSS score or retention rate at the follow-up. There was no interaction between the investigated polymorphisms and response to the antipsychotic treatment.ConclusionsThe present results suggest that: i) there are no major differences in short-term efficacy or effectiveness of atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs; ii) the studied polymorphisms are not primarily involved in treatment response to antipsychotics in schizophrenia patients.     

齐拉西酮治疗男性与女性精神分裂症的疗效与安全性对比研究

目的:比较齐拉西酮治疗男性与女性精神分裂症患者的疗效及安全性。方法:25例男性(男性组)和64例女性(女性组)精神分裂症患者均接受齐拉西酮治疗8周。于治疗前后采用阳性与阴性症状量表(PANSS)评定疗效,并通过体检、实验室和心电图检查以及其他不良事件的描述性记录资料评价其安全性。结果:总显效率男性组和女性组分别为80.0%和78.13%(P=0.53)。两组PANSS总分及各项评分治疗后均较治疗前显著下降(P0.05或P0.01);PANSS总分及一般病理症状减分值女性组较男性组明显增高(t=-2.27~-2.53;P0.05或P0.01)。女性组治疗后心电图QTc间期(t=-3.04,P=0.00)、体质量(t=-2.81,P=0.00)和三酰甘油(t=-2.82,P=0.01)明显上升;中性粒细胞(t=2.06,P=0.04)、总蛋白(t=2.10,P=0.04)、空腹血糖(t=2.34,P=0.02)明显下降。不良反应发生率男性组和女性组分别为20%和18.75%(P0.05)。结论:齐拉西酮对男性和女性精神分裂症患者均具有良好的疗效和安全性;但对女性患者QTc间期、体质量、空腹血糖及血脂的影响较大。     

齐拉西酮联合小剂量奎硫平治疗首次发病老年精神分裂症患者的对照研究

目的:探讨齐拉西酮联合小剂量奎硫平及齐拉西酮单药治疗首次发病的老年精神分裂症患者的疗效及对糖脂代谢的影响。方法:72例首次发病的老年期精神分裂症患者随机分为齐拉西酮联合小剂量奎硫平组(研究组)和齐拉西酮组(对照组)各36例,疗程8周。治疗前后给予阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI-SI)及治疗中出现的症状量表(TESS)评定,比较两组体质量、血糖及血脂的变化。结果:治疗后两组PANSS及CGI-SI总分均较治疗前明显下降(P均0.01);且研究组减分明显多于对照组(P0.05或P0.01);总有效率研究组(88.9%)明显高于对照组(77.8%)(Z=2.101,P0.05)。治疗后两组血糖及血脂水平无明显变化且两组间差异无统计学意义;研究组体质量较治疗前及对照组明显增加(P均0.05);两组TESS评分和药物不良反应发生率比较差异无统计学意义。结论:齐拉西酮联合小剂量奎硫平治疗首次发病的老年精神分裂症患者的疗效优于单用齐拉西酮治疗,对血糖、血脂影响较小,但导致体质量的增加。     

合曲林联合小剂量齐拉西酮治疗强迫症对照研究

目的探讨舍曲林联合小剂量齐拉西酮治疗强迫症的临床疗效和安全性。方法将76例强迫症患者随机分为研究组和对照组各38例,均口服舍曲林治疗,研究组联合小剂量齐拉西酮治疗,观察12周。于治疗前及治疗4周、8周、12周末采用Yale—Brown强迫量表评定l临床疗效,并随时记录不良反应发生状况。结果治疗后两组Yale—Brown强迫量表总分及各因子分均较治疗前显著下降（P〈0．05或0．01）,治疗8周、12周末研究组较对照组下降更显著（P〈0．01）;研究组起效时间显著早于对照组,治疗12周末总有效率显著高于对照组（P〈0．05）;两组不良反应均轻微,发生率比较差异无显著性（P〉0．05）。结论舍曲林联合小剂量齐拉西酮治疗强迫症疗效显著,起效快,不增加不良反应,显著优于单用舍曲林治疗。     

甲磺酸齐拉西酮对老年精神分裂症患者的临床疗效

目的探讨甲磺酸齐拉西酮治疗精神分裂症患者急性激越症状的临床效果。方法选取2016年1月至2017年12月在四川省广元市精神卫生中心接受治疗的老年精神分裂症患者72例。采用随机数字表法将患者分为甲磺酸齐拉西酮组、氟哌啶醇组各36例。甲磺酸齐拉西酮组患者给予注射用甲磺酸齐拉西酮5~10 mg/次,肌内注射,每日总量不大于20 mg;氟哌啶醇组患者给予常规氟哌啶醇针剂5 mg/次,肌内注射,每日总量不大于10 mg。记录并比较2组患者治疗前及治疗72 h的阳性和阴性症状量表(PANSS)、临床疗效总体印象量表之病情严重程度(CGI-SI)评分,以及治疗前(T0)和治疗后2 h(T1)、8 h(T2)、24 h(T3)、48 h(T4)、72 h(T5)阳性和阴性症状量表中的兴奋因子(PANSS-EC)评分。采用SAS 9. 0软件进行统计分析。根据数据类型,组间比较采用独立样本t检验或χ2检验,治疗前后比较采用配对t检验。结果治疗前及治疗72 h后的2组患者PANSS及CGI-SI评分比较,差异无统计学意义(P 0. 05),治疗72 h后,2组患者PANSS及CGI-SI评分较治疗前均显著降低,差异有统计学意义(P 0. 05)。治疗前、后各时间点2组患者PANSS-EC评分差异无统计学意义(P 0. 05);与T0比较,T1-5各时间点2组患者PANSS-EC评分均显著降低,差异有统计学意义(P 0. 05);与T1比较,T2-5各时间点2组患者PANSS-EC评分均显著降低,差异亦有统计学意义(P 0. 05)。与氟哌啶醇组比较,甲磺酸齐拉西酮组患者肌强直[2. 78%(1/36) vs 16. 67%(6/36)]、震颤[2. 78%(1/36) vs 19. 44%(7/36)]、流涎[5. 56%(2/36) vs 22. 22%(8/36)]、头颈部运动[2. 78%(1/36) vs 19. 44%(7/36)]等副反应发生率显著降低,差异有统计学意义(P 0. 05)。结论甲磺酸齐拉西酮治疗精神分裂症急性激越症状患者的效果与常规氟哌啶醇相似,同时具有副作用发生率较低的优点。     

Are Oral Medications Effective in the Management of Acute Agitation?

Background

Current expert guidelines recommend treating agitation with oral medications instead of intramuscular medications if possible. Oral medications are sometimes believed to be inappropriate for the emergency department (ED) as they require patient cooperation and may have a slower onset of action. This review examined published literature for the efficacy of oral agents in agitation.Clinical question: Are oral medications effective at managing acute agitation?

Methods

Structured review of PubMed of articles in which the first timepoints of evaluation were < 24 hours (i.e., the typical timecourse in the ED).

Results

11 articles included for final analysis.

Conclusions/Clinical Bottom Line

Treatment with oral medications is as effective as intramuscular medications in rapidly reducing psychotic agitation in the ED. Their use is thought to pose less risk to both patient and ED staff and is less coercive. There is little to no evidence about the use of oral medications for ED patients with extreme agitation.     

齐拉西酮利培酮和氯丙嗪对首发精神分裂症患者认知功能的影响

目的：探讨齐拉西酮、利培酮和氯丙嗪治疗对首发精神分裂症患者认知功能的影响。方法将96例首发精神分裂症患者随机分成3组,每组32例,分别口服齐拉西酮、利培酮和氯丙嗪治疗,观察8周。于治疗前后采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应,威斯康星卡片分类测验、数字划消测验和修订韦氏成人记忆量表评定认知功能。结果治疗8周末齐拉西酮组总有效率为86．67％,利培酮组为83．33％,氯丙嗪组为85．71％,3组总有效率比较差异无显著性（P＞0．05）;齐拉西酮组、利培酮组认知功能各项测验指标均较治疗前有显著改善（P＜0．01）,氯丙嗪组则无显著变化（P＞0．05）;齐拉西酮组和利培酮组不良反应发生率显著低于氯丙嗪组（P＜0．05）。结论齐拉西酮、利培酮和氯丙嗪治疗首发精神分裂症疗效显著且相当,但齐拉西酮和利培酮能改善患者的认知功能,安全性更高,显著优于氯丙嗪治疗。