Aripiprazole: a partial dopamine D2 receptor agonist antipsychotic

This paper reviews the clinical pharmacology, efficacy and safety of the novel antipsychotic drug aripiprazole. All published citations regarding aripiprazole were reviewed using a Medline^® search (completed for citations through mid-year, 2002). In addition, abstracts from recent scientific meetings presenting data not yet published (nor peer-reviewed) were reviewed. Aripiprazole has a unique mechanism of action as a dopamine D2 partial agonist, serotonin 5-HT_1A partial agonist and serotonin 5-HT_2A antagonist. Like other new antipsychotics, aripiprazole has the profile of an atypical agent, with efficacy in the treatment of positive and negative symptoms of psychosis as well as mood symptoms, a low rate of neurological side effects and no significant adverse effect on serum prolactin concentrations. In addition, aripiprazole was not associated with significant weight gain or QTc prolongation in both acute and long-term treatment trials.     

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.     

Aripiprazole for treating irritability associated with autism spectrum disorders

ABSTRACT

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a reported prevalence of 1 in 59 people. Its core features are persistent deficits in social communication and restricted, repetitive patterns of behavior or interests. Individuals with ASD have a high incidence of secondary problems with mood lability, tantrums, self-injurious behavior and aggressiveness toward others. Collectively, these behaviors are often referred to as irritability. Many medications have been used to treat irritability in autism, with aripiprazole one of only two medications approved in the USA for this purpose.

Areas covered: Herein, the authors review the evidence supporting the use of aripiprazole for treating irritability in autism, including the pivotal trials leading to regulatory approval and long-term studies conducted post-approval. They utilized PubMed, searching all English language publications since 2000, using the terms aripiprazole, autism, autism spectrum disorder, pervasive developmental disorder, Asperger’s disorder, and irritability, and focused on clinical trials and review articles.

Expert opinion: Multiple studies have shown the clear benefit of aripiprazole in the treatment of irritability in autism disorders compared to placebo. Often underemphasized are the metabolic effects, the proper monitoring for these effects, and the need for periodic reassessment to determine if ongoing treatment is needed.     

阿立哌唑的临床应用研究进展

【摘要】 目前非典型抗精神病药物阿立哌唑在精神科的临床使用日趋广泛,不但应用于精神分裂症的治疗,作为心境稳定剂治疗情感障碍,而且应用于抑郁症、强迫症、老年性痴呆、儿童抽动症等的治疗,在精神疾病的治疗中发挥了较好的作用,已经成为精神科药物治疗的重要手段,本文对阿立哌唑的临床应用作一综述,以期为临床用药提供参考。     

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.     

阿立哌唑与氯氮平对精神分裂症患者心电图的影响

目的 探讨阿立哌唑与氯氮平对精神分裂症患者心电图的影响.方法 将95例精神分裂症患者随机分为研究组(48例)和对照组(47例),分别应用阿立哌唑与氯氮平治疗.观察8周.于治疗前及治疗后第4周、8周末进行心电图检查.结果 阿立哌唑组窦性心动过速、T波改变、S-T段改变、Q-T间期延长发生率均显著低于氯氮平组(P＜0.05或0.01);治疗第4周、8周末,阿立哌唑组心电图异常发生率分别为12.50%、20.83%,氯氮平组分别为53.19%、68.09%,同期两组间比较差异均有极显著性(P＜0.01).结论 阿立哌唑和氯氮平对精神分裂症患者的心电图均有影响,但阿立哌唑致心电图改变发生率低于氯氮平,程度较轻,安全性相对较高.     

Acute masseter dystonia in a pediatric patient receiving aripiprazole and methylphenidate following induction of general anesthesia

An 11‐year‐old male receiving aripiprazole, methylphenidate, and clonidine developed acute masseter dystonia inhibiting tracheal intubation after induction of general anesthesia with propofol and rocuronium. Following emergence, he had trismus and jaw discomfort. Psychiatry consultation suspected an acute dystonic reaction, so diphenhydramine was administered intravenously which resolved symptoms. We suspect chronic aripiprazole and methylphenidate usage combined with propofol administration in the short‐term absence of methylphenidate made this patient susceptible to dystonic reactions.     

阿立哌唑在酸性溶液中的降解动力学研究

目的研究阿立哌唑在酸性溶液中的降解动力学。方法通过经典恒温实验,采用HPLC法测定阿立哌唑在不同温度、pH值、缓冲液种类及质量浓度的降解动力学参数,用Arrhenius公式预测其活化能。结果阿立哌唑在酸性溶液中最稳定的pH值为4.0。随着温度增加,阿立哌唑的降解加快,其活化能Ea=117.60kJ·mol~(-1)。阿立哌唑在枸橼酸盐中的降解速率最快,在磷酸盐及醋酸盐中相对较慢。结论阿立哌唑在酸性溶液中的降解近似一级动力学过程,与温度和缓冲盐质量浓度呈正相关,pH值对其降解速率影响显著,缓冲盐种类的不同对其降解速率影响较明显。本研究为该制剂的研究开发提供了必要的数据支持。     

阿立哌唑自乳化释药系统的制备与质量评价

目的 制备阿立哌唑自乳化释药系统（ARP-SEDDSs）以提高药物的口服生物利用度。方法 HPLC法检测ARP在不同的油、表面活性剂和助表面活性剂中的溶解度,根据溶解度确定处方组成;采用伪三元相图筛选SEDDSs的处方比例;通过动态光散射、透射电镜、稀释稳定性和体外溶出对ARP-SEDDSs进行表征;大鼠分别ig给予自制ARP-SEDDSs和ARP混悬液（20 mg·kg^-1）后,HPLC法进行药动学研究,考察大鼠ig ARP-SEDDSs的生物利用度。结果 以油酸作为油相,以聚乙二醇15-羟基硬脂酸酯和异丙醇作为表面活性剂和助表面活性剂,优化得到ARP-SEDDSs处方为油酸-聚乙二醇15-羟基硬脂酸酯-异丙醇为2.0∶5.6∶2.4,载药量为10 mg·g^-1;ARP-SEDDSs经水稀释后可快速形成微乳,在透射电镜下可观察到微乳呈类球形,经动态光散射仪检测其平均粒径为（54.6±2.3）nm,聚合物分散性指数（PDI）为0.201±0.011,Zeta电位（-13.5±0.4）mV;ARP-SEDDSs在pH 6.8磷酸盐缓冲液中10 min的药物溶出度接近100%,远高于阿立哌唑口崩片（约10%）。大鼠体内药动学研究表明,与ARP混悬液相比,ARP-SEDDSs相对生物利用度为248.8%。结论 将ARP制备成自乳化释药系统,有助于药物快速溶出,显著提高了ARP的口服生物利用度。