阿立哌唑与氯氮平治疗精神分裂症对照研究

目的：比较阿立哌唑与氯氮平治疗精神分裂症的临床疗效与安全性。方法：将精神分裂症患者100例随机分为阿立哌唑组与氯氮平组。疗程12周。采用阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）、健康状况问卷（SF-36）评定疗效及不良反应。结果：两组治疗后PANSS评分均显著下降，两组问比较差异无显著性（P〉0．05）。不良反应发生率阿立哌唑组显著低于氯氮平组（P〈0．05）。结论：阿立哌唑治疗精神分裂症疗效与氯氮平相仿，不良反应少，是一种安全有效的抗精神病药。     

Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease.

Psychosis affects at least 5% to 8% of medication-treated patients with idiopathic Parkinson's disease (PD). Treatment options include reducing medications used for the treatment of PD-related motor symptoms or introducing an atypical antipsychotic drug. Only clozapine has been demonstrated to be efficacious and tolerated in double-blind controlled trials. This study evaluated the effect of aripiprazole, an atypical antipsychotic, on psychosis in PD in an open-label pilot study. Fourteen patients meeting entry criteria were started on aripiprazole 1 mg/day and titrated up to a maximum dose of 5 mg as needed. Subjects were evaluated on the Unified Parkinson's Disease Rating Scale (UPDRS) part III for motor function, the Neuropsychiatric Inventory (NPI), and the Brief Psychiatric Rating Scale (BPRS) for psychiatric response. Statistically significant improvement in mean BPRS and positive BPRS subscales occurred with open-label aripiprazole, but eight subjects discontinued the study due to worsened Parkinsonism (three), worsened psychosis (two), worsening of both (two), and lack of efficacy (one). While some patients had a favorable response, aripiprazole was associated with an exacerbation of motor symptoms. In this small study on psychosis in PD, aripiprazole did not appear promising.     

Aripiprazole in the acute treatment of male patients with schizophrenia: effectiveness, acceptability, and risks in the inner-city hospital setting

Aripiprazole, a novel atypical antipsychotic that acts as a partial agonist at the dopamine D₂ receptors, has been reported to be effective in the treatment of chronic schizophrenia. However, the risks and benefits of using aripiprazole in the acute hospital setting to treat severe psychotic disorders are unclear. This naturalistic study assessed the effectiveness of aripiprazole monotherapy in a group of actively psychotic male patients (n = 10) with schizophrenia who were admitted to an inner-city acute psychiatric unit. Most patients (n = 7) responded to aripiprazole treatment, which was well tolerated and significantly ameliorated psychotic symptoms after 2–3 weeks. Patients who responded to it could be safely discharged on aripiprazole monotherapy. Side effects observed were mostly mild and transient, and included extrapyramidal symptoms (n = 1) and neutropenia (n = 1). Aripiprazole also remarkably attenuated dyskinetic movements in 1 patient with severe tardive dyskinesia, thereby suggesting that it may be useful in the treatment of other disorders that are also associated with dopamine dysfunction. Results showed that aripiprazole can be safely and effectively employed in the hospital setting to treat severely psychotic patients with schizophrenia, but further studies are required to establish the full range of adverse reactions and therapeutic indications associated with its use.     

阿立哌唑合用文拉法辛治疗难治性抑郁症

目的探讨阿立哌唑合用文拉法辛治疗难治性抑郁症的疗效和安全性。方法将72例难治性抑郁症病人随机分成阿立哌唑合用文拉法辛组(研究组,n=36)与单用文拉法辛组(对照组,n=36),文拉法辛剂量:起始25 mg,bid,7～10 d内加至175～300 mg·d~(-1);阿立哌唑剂量:5 mg·d~(-1),治疗6 wk。用HAMD,HAMA,TESS量表评定疗效和不良反应。结果2组间HAMD,HAMA于wk 1,2,6末减分率比较差异均有非常显著意义(P<0.01),6 wk末研究组有效率86%,对照组56%,2组差异有显著意义(P<0.05),不良反应均表现较轻,大多出现在治疗早期,经对症治疗逐渐缓解。结论阿立哌唑合用文拉法辛治疗难治性抑郁症的疗效优于单用文拉法辛,且耐受性好。     

反相高效液相色谱法测定人血浆中阿立哌唑的浓度

目的:建立测定人血浆中阿立哌唑浓度的HPLC法。方法:以D iamonsilTMC18反相柱(250mm×4.6mm,5μm)为色谱柱,流动相为甲醇-0.03mol.L-1醋酸铵(90∶10),流速为0.8mL.m in-1,检测波长257nm,以乙醚为提取剂。结果:阿立哌唑的高(500μg.L-1)、中(100μg.L-1)、低(20μg.L-1)3个浓度的提取回收率分别为93.51%,93.23%,96.51%,日内、日间RSD均小于6%;分析方法的最低定量限为5μg.L-1。线性范围为5~500μg.L-1,回归方程为C=376.24F-5.48,r=0.999 7(n=9)。结论:该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究。     

新型非典型抗精神病药临床应用评价

目前非典型抗精神病药应用越来越广泛,有逐渐取代典型抗精神病药的趋势,不但用于精神分裂症的治疗,而且作为心境稳定剂治疗情感障碍。本文对非典型抗精神病药的概念、治疗阴性症状和较少锥体外系不良反应的机制、在精神分裂症和情感障碍治疗中的临床应用评价等文献进行综述,重点讨论奥氮平、利司哌酮、喹硫平、阿立哌唑、齐哌西酮、氨磺必利和哌罗匹隆。     

阿立派唑与利培酮治疗门诊首发精神分裂症的临床研究

目的比较阿立派唑与利培酮治疗首发精神分裂症的疗效和安全性。方法将70例符合CCMD-3和DSM-Ⅳ的精神分裂症诊断标准的首发病人随机分为两组,分别给予阿立派唑和利培酮治疗8周。在治疗前及治疗2、4、6、8周时采用阳性症状和阴性症状量表(PANSS)评定临床疗效,副反应量表(TESS)评定副反应。结果治疗8周后的疗效近似(P>0.05);阿立派唑组和利培酮组的显效率差异无显著性(P>0.05);阿立派唑组的副反应发生率低于利培酮组,且差异有显著性(P<0.01)。利培酮组锥体外系副反应和内分泌改变的发生均明显高于阿立派唑组(P<0.01)。两药的副作用均以轻、中度多见。结论阿立派唑和利培酮对首发精神分裂症的疗效相当,依从性好,副作用方面有一定的差异。     

阿立哌唑的合成

4-（2，3-二氯苯基）-1-哌嗪盐酸盐与1，4-二溴丁烷缩合得到1-（4-溴丁基）-4-（2，3-二氯苯基）哌嗪，再与3-氯-N-（3-羟基苯基）丙酰胺反应得3-氯-N-[3-[4-[4-（2，3-二氯苯基）]-1-哌嗪基]丁氧基]苯丙酰胺，最后经闭环制得阿立哌唑，总收率25％。     

Favourable results in treatment-resistant schizophrenic patients under combination of aripiprazole with clozapine

Clozapine is still the gold standard in treatment-resistant schizophrenia. However, a substantial amount of patients do not fully recover on clozapine monotherapy. Though there is still a lack of randomised controlled studies of combination strategies in treatment-resistant schizophrenia, they are widely used. Aripiprazole is a relatively new therapeutic option due to its partial D2 agonism. Both clozapine and aripiprazole, though having a generally favourable side-effect profile, may lead to insufficient response and might provoke side effects in monotherapy. We report the case of four patients in whom we observed a distinct clinical improvement with respect to positive and negative symptoms without major side effects under a combination of clozapine and aripiprazole. The combination of clozapine action and aripiprazole-mediated D₂ receptor regulation could be responsible for the described favourable effects and for the increase of D₂ receptor blockade after adding aripiprazole to clozapine observed in one patient. A combination of clozapine and aripiprazole may be an effective therapeutic strategy for some schizophrenic patients, leading to a good response with respect to positive and negative symptoms without the occurrence of major side effects.