非典型抗精神病药所致血脂异常的研究进展

随着非典型抗精神病药物的广泛使用,其产生的不良反应日益受到人们的关注。文章首先介绍了非典型抗精神病药物所致血脂异常的发生率、类型和程度,以及既往研究中不同药物所致血脂异常的比较,随后探讨了导致血脂异常发生的相关因素(包括性别、年龄、种族、体重),及其可能存在的神经内分泌和基因方面的生物学机制,最后提出了今后该领域的研究方向及血脂异常的防治措施,为非典型抗精神病药物所致血脂异常的进一步研究和防治工作提供参考。     

新一代非典型抗精神病药

对近几年出现的一些非典型抗精神病药物利培酮、奥氮平、喹硫平、齐拉西酮、舒吲哚进行了分析,并讨论了这些新药的作用机制、不良反应、临床应用、过量时危险及处理等几个方面的问题。     

非典型抗精神病药的临床应用评价

以氯丙嗪为代表的典型抗精神病药在二十世纪六十年代开始使用时,是一种能有效控制精神病症状的药物,治疗精神分裂症很有效.虽然它们在药效和化学组成上有很大的差别,但也具有很多共同点.它们的药理学作用是阻断多巴胺D2受体.疗效包括控制严重的精神病症状,减少攻击性行为,缓解严重的焦躁,降低精神分裂症和其它精神病患者在维持治疗期间病情复发的危险.所有的典型抗精神病药都会产生锥体外系副作用,因此它们被称为精神抑制药[1].     

新型非典型抗精神病药齐拉西酮

通过文献检索综述了齐拉西酮的作用机制、药代动力学及临床评价。齐拉西酮是一种安全、有效的非典型性抗精神病药，用于治疗精神分裂症和分裂情感性障碍。     

非典型抗精神病药——Ziprasidone

Ｚｉｐｒａｓｉｄｏｎｅ是一种非典型抗精神病药 ,它的结构与其它抗精神病药不相关 ,药效作用也不同。它是５ -ＨＴ２ａ、Ｄ２、５ -ＨＴ２ｃ 和５ -ＨＴ１ｄ 受体拮抗剂 ,也是５ -ＨＴ１ａ 受体激动剂和５ -ＨＴ、去甲肾上腺素重摄取抑制剂 ,其消除相Ｔ１／２ 可达１０ｈ ,饭后立即服用 ,ｂｉｄ ;老年人、轻度肾衰竭者或中度肝衰竭者勿需改变剂量。该药可能参与极少的药代动力学相互作用 ,对已知的细胞色素酶抑制作用不明显。人体的药效学研究表明 ,本品对精神分裂症和分裂情感性疾病的耐受性好 ,很少引起锥体外系副作用以及与高催乳血症有…     

非典型抗精神病药的较高花费是否值得

关于非典型抗精神病药物的应用，在12月的Australian Prescriber上发表了两种针锋相对的观点。双方都强调了非典型抗精神病药物的一些重要特点，其中包括，相比于传统的药物而言，这些非典型抗精神病药物较少或没有锥体外系的副作用。     

非典型抗精神病药的临床应用及不良反应

目的:对近几年出现的一些非典型抗精神病药物利培酮、奥氮平、奎的平、思普酮、思庭多进行介绍,并讨论这些药物的作用机制,临床应用,不良反应及经济学评价等问题.方法:通过查阅相关文献并进行综述.结果:这类药物的作用机制可能与多巴胺受体(D2)、5-羟色胺受体(5-HT)受体的联合阻断有关,具有用药简单,疗效显著,耐受性及安全性良好等优点,但仍然不可避免地存在一定的不良反应.结论:新一代非典型抗精神病药在改善精神分裂症的阳性,阴性症状以及安全性,耐受性方面明显优于传统抗精神病药,但仍应注意不良反应.     

非典型抗精神病药治疗难治性抑郁症的疗效观察

目的观察非典型抗精神病药治疗难治性抑郁症的疗效。方法回顾性分析采用一般抗抑郁药治疗无效的40例难治性抑郁症患者,在合并非典型抗精神病药治疗6周后,比较合并非典型抗精神病药治疗6周和合并用药前一般治疗的临床疗效和HAMD、HAMA评分及不良反应。结果合并非典型抗精神病药前一般治疗均无效。合并非典型抗精神病药6周时,总有效率为70％高于合并前的疗效。合并非典型抗精神病药后,姒MD、HAMA评分均低于治疗前,差异有统计学意义（P〈0．05）。合并用药前后不良反应发生率差异无统计学意义（P〉0．05）。结论非典型抗精神病药物增加了抗抑郁药的疗效,未增加药物不良反应。     

非典型抗精神病药治疗难治性抑郁症

目的观察并研究难治性抑郁症患者应用非典型抗精神病药进行治疗的临床效果。方法选取2016年8月至2018年10月来我院接受治疗的82例难治性抑郁症患者为例,按入院顺序将其分成两组,给予对照组患者一般治疗,也即在常规抗抑郁药治疗无效后,采取替换法或加强法展开治疗;观察组则在一般治疗的基础上联合应用非典型抗精神病药。统计两组患者的药物治疗效果,并展开对比与评价。结果①心理状态改善方面,观察组患者HAMA(汉密顿焦虑量表)与HAMD(汉密顿抑郁量表)评分下降幅度显著大于对照组,数据差异明显,P <0.05,存在统计学意义。②治疗总有效率方面,观察组高达85.4%,相比于对照组的68.3%明显升高(P<0.05)。③不良反应发生率方面,观察组与对照组分别为12.2%与17.1%,数据差异不大,无统计学意义(P> 0.05)。结论对于难治性抑郁症患者,通过应用非典型抗精神病药进行治疗,可有效改善患者的心理状态,提高抗抑郁药的治疗效果,且不会增加不良反应,值得重视。     

非典型抗精神病新药研究进展

精神分裂症发病机制复杂,治疗药物多以缓解症状为主要目的 ,临床尚无能有效治愈精神分裂症的药物。本文回顾了2007年以来美国食品药品管理局批准上市的治疗成人精神分裂症的非典型抗精神病药物,以期对精神分裂症的治疗提供参考。     

新型非典型抗精神病药:鲁拉西酮

鲁拉西酮为一新型非典型抗精神病药,属于苯并异噻唑衍生物,为多巴胺D_2和5-羟色胺2A(5-HT_(2A))受体拮抗剂。2010年10月28日美国食品和药物管理局批准鲁拉西酮上市,其商品名为Latuda,用于治疗成人精神分裂症。鲁拉西酮的有效剂量范围为40～120mg·d~(-1),推荐起始剂量为40mg·d~(-1),一般最大推荐剂量为80mg·d~(-1),应与食物同时服用。鲁拉西酮常见不良反应有嗜睡、静坐不能、恶心、帕金森病以及焦虑。本文对鲁拉西酮的药理作用、药动学、药物相互作用、临床评价和安全性等进行综述。     

Cost-effectiveness of atypical antipsychotic medications versus conventional medication

For almost 50 years, typical antipsychotics were the mainstay of pharmacological treatment for schizophrenia. However, during the last decade, the widespread use of expensive atypical antipsychotic medications has led to a dramatic increase in the proportion of the direct costs of schizophrenia being allocated for medications. Although there is evidence that the atypical antipsychotic clozapine may lead to cost savings in patients with refractory schizophrenia, the cost-effectiveness of the other atypical antipsychotics remains in question. Therefore, long-term randomised, prospective cost-effectiveness studies that compared an atypical to a typical antipsychotic have been reviewed in this paper. There were serious methodological problems with all the studies. In general, those that were based on efficacy trials showed an advantage for atypicals, whereas those based on effectiveness studies found the opposite. It seems that, to the extent that studies mimic real world conditions, they fail to support the cost-effectiveness of the atypical antipsychotics.     

新型抗精神病药：哌罗匹隆

哌罗匹隆是一种新型非典型抗精神病药,主要药理机制是5-羟色胺(5-HT)和多巴胺D_2受体拮抗作用。与传统抗精神病药相比,哌罗匹隆对阳性症状、阴性症状和情感症状均有较好疗效,锥体外系不良反应和致催乳素升高作用轻微。哌罗匹隆是一种安全有效的非典型抗精神病药。     

Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic

Ziprasidone (5-[2-(4-(1,2,-benzisothiazol-3-yl) piperazin-l-yl] ethyl]-6 -chloro indolin-2-one hydrochloride hydrate) is a novel antipsychotic with a pattern of receptor occupancy and preclinical attributes predictive of broad therapeutic efficacy and a favourable tolerability profile in the treatment of psychotic illness. Clinical trials indicate that ziprasidone is effective against positive, negative and affective symptoms in schizophrenia and schizoaffective disorder with minimal motor, cognitive, weight gain, prolactin related, or anticholinergic side effects. In addition, an im. formulation appears to be rapidly effective with significantly less motor side effect liability than haloperidol.     

An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

ABSTRACT

Background: This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated.

Methods: Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals.

Results: The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age-adjusted OR = 0.89, 95% CI = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10-year age increment (p-value < 0.0001).

Conclusions: This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.     

Ziprasidone: a new atypical antipsychotic

This paper reviews the clinical pharmacology, efficacy and safety of the new atypical antipsychotic, ziprasidone. All published citations regarding ziprasidone were retrieved and reviewed using a Medline^® search (completed for citations to early 2001). In addition, abstracts from recent scientific meetings presenting data not yet published were reviewed. Like other new antipsychotic medications, ziprasidone fits the profile of an atypical agent, exerting efficacy in positive and negative symptoms of psychosis, as well as affective symptoms, with a low risk of neurological and neuroendocrinological side effects. Unlike newer agents, it does not appear to be associated with weight gain in most patients.     

Recent advances towards the discovery of dopamine receptor ligands

Dopamine is a key regulator in the CNS, contributing importantly to functions of arousal and attention, initiation of movement, perception, motivation and emotion. Its imbalance has been implicated in the pathophysiology, and more clearly in the pharmacology, of a number of neurobehavioural disorders, including Parkinson’s disease, schizophrenia, mania and depression, alcohol and drug abuse, as well as attention and eating disorders. Five major dopamine receptor subtypes (D1 – D5) have been identified, with distinct differences in their genes and peptide composition, molecular functions and neuropharmacology. These receptors represent the rational targets for the treatment of a large number of neurological and psychiatric disorders. In recent years, substantial efforts have addressed the most recently described dopamine receptor types, particularly types D3, D4 and D5, although most research involves the longer-known D1 and D2 dopamine receptors. Current pharmacological efforts in medicinal chemistry and neuropharmacology include the development of D1 full agonists and D2 partial agonists, as well as agents with dopaminergic activity combined with effects at CNS serotonergic, muscarinic, adrenergic and histaminic receptors. This review provides an overview of the recent patent literature during 2003 – 2005 on the development of therapeutic agents, mainly targeting the five dopamine receptors.     

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient’s emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.