阿戈美拉汀抗抑郁应用的现状与进展

目的:为促进阿戈美拉汀在治疗抑郁症中的合理应用提供参考。方法:通过查阅近期国内外对阿戈美拉汀的研究资料,对阿戈美拉汀的作用机制,药理学特性,临床应用中的起始治疗、停药、换药及联合治疗、对睡眠的影响,以及其耐受和安全性进行归纳和总结。结果与结论:阿戈美拉汀的不良反应小、促进睡眠作用较好,且撤药反应微弱,易与其他药物联用,是药理学特性新颖、临床应用前景广阔的抗抑郁药物。     

警惕阿戈美拉汀的肝脏毒性

2014年9月26日,欧洲药品管理局（ EMA）发布安全信息,指出抗抑郁药阿戈美拉汀的治疗效果优于其风险,但治疗期间应密切关注患者肝功能的变化,以防范药物的肝毒性。抑郁症是一种严重威胁人类健康的精神疾患,近年来各种新型抗抑郁药相继问世。新型褪黑素受体激动剂阿戈美拉汀就是其中一员。阿戈美拉汀是褪黑素类似物,可选择性激动褪黑素MT1、MT2受体,同时它还可拮抗5．羟色胺2C（S-HTx）受体,从而产生抗抑郁、抗焦虑及调整睡眠节律的作用。最新的多中心临床研究显示阿戈美拉汀的抗抑郁效果优异。     

药物警戒快讯

1欧盟进一步加强阿戈美拉汀肝损害风险警告 2014年9月26日,欧洲药品管理局（EMA）发布消息称,已完成对抗抑郁药阿戈美拉汀的审查,结论是该药品的获益仍大于风险。然而,EMA建议应采取进一步的措施,使发生肝毒性的风险降至最低。阿戈美拉汀用于治疗成人重症抑郁症。2009年2月在欧盟首次获得批准,现已在所有欧盟国家及冰岛上市。     

盐酸阿戈美拉汀与盐酸帕罗西汀治疗重症抑郁症的疗效和安全性研究

目的:研究阿戈美拉汀和帕罗西汀治疗重症抑郁症的疗效,安全性和耐受性.方法:选取医院2017年12月至2019年12月80例诊断为重度抑郁症的患者,依据随机抽签法分为阿戈美拉汀组(40例)与帕罗西汀组(40例).帕罗西汀组患者接受帕罗西汀20～40 mg·d-1,而阿戈美拉汀组患者接受阿戈美拉汀25～50 mg·d-1....     

阿戈美拉汀治疗抑郁症的研究进展

目的:为阿戈美拉汀的临床应用提供参考。方法:以"阿戈美拉汀""抑郁症""安全性""有效性""Agomelatine""Depression""Security""Effectiveness"等为关键词,组合查询2000年1月-2018年12月在中国知网、万方数据、PubMed、Medline、Science Direct等数据库中的相关文献,对阿戈美拉汀的药理作用机制、临床有效性和不良反应进行综述。结果与结论:共检索到相关文献242篇,其中有效文献52篇。阿戈美拉汀是首个靶向褪黑素的抗抑郁药物,具有调节昼夜节律的作用,对抑郁情绪及睡眠改善显著,具有对体质量及性功能影响小、耐受性好、撤药反应小等优势,其作用机制与激动褪黑素MT1/MT2受体和拮抗五羟色胺2c(5-HT2c)、5-HT2b受体等有关。阿戈美拉汀对抑郁症急性期、维持期患者及老年抑郁症患者具有明显疗效;与五羟色胺去甲肾上腺素再摄取抑制剂(SSRI)类抗抑郁药物(艾司西酞普兰、帕罗西汀、氟西汀等)和其他类抗抑郁症药物(沃替西汀、米氮平、文拉法辛等)疗效相当;其在治疗过程中常见不良反应有头痛、头晕、腹泻、恶心、转氨酶升高等,因此,建议在临床使用时应注意监测其不良反应。     

阿戈美拉汀治疗抑郁症伴睡眠障碍的疗效和安全性的系统评价

目的:基于荟萃分析(Meta分析)方法,系统评价阿戈美拉汀对抑郁症伴睡眠障碍患者的睡眠改善效果及其安全性,为临床治疗提供循证参考。方法:检索PubMed、the Cochrane Library、EMBase、中国知网、万方数据库和维普数据库,纳入从建库至2020年4月公开发表的关于阿戈美拉汀治疗抑郁症伴睡眠障碍患者的中英文文献[研究组患者单独使用阿戈美拉汀口服治疗,对照组患者单独使用5-羟色胺再摄取抑制类抗抑郁药(米氮平、帕罗西汀或艾司西酞普兰等)治疗或阿戈美拉汀联合其他药物治疗],提取汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分和匹茨堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)相关数据,采用Rev Man 5.3软件进行文献质量评价和Meta分析。结果:共纳入8项研究,合计332例患者。Meta分析结果显示,抑郁症伴睡眠障碍患者单独使用阿戈美拉汀治疗后,其HAMD评分(SMD=-5.31,95%CI=-6.28~-4.33,P<0.00001)、PSQI总分(SMD=-3.66,95%CI=-4.16~-3.17,P<0.00001)均较治疗前明显降低,差异均有统计学意义。结论:阿戈美拉汀对抑郁症伴睡眠障碍患者的抑郁症状和失眠症状均有较好的改善作用,但受纳入研究的质量和样本量限制,该结论需大样本、多中心、长时间的随访结果进行验证。     

阿戈美拉汀多晶型研究

目的研究抗抑郁药阿戈美拉汀的多晶型现象。方法比较阿戈美拉汀不同晶型的制备方法,采用红外光谱和粉末X-射线衍射法测定不同晶型的特征。结果发现了阿戈美拉汀的一种新晶型(Ⅹ型),并通过红外光谱和粉末Ⅹ-射线衍射法确定其不同于文献报道的Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵ等6种晶型。结论初步稳定性研究结果表明,阿戈美拉汀Ⅹ晶型具有适合作为药物应用的潜力。     

阿戈美拉汀联合认知行为疗法治疗首发抑郁症的临床疗效分析

目的 探讨阿戈美拉汀联合认知行为疗法治疗首发抑郁症的临床疗效.方法 选取2019年2月～2021年2月收治的150例首发抑郁症患者,随机分为观察组与对照组,每组75例.对照组患者接受阿戈美拉汀治疗,观察组患者接受阿戈美拉汀联合认知行为疗法干预.疗程结束后,分别记录两组患者的HAMD-17量表评分、综合治疗效果,并比较不...     

阿戈美拉汀对SD大鼠的长期毒性评价研究

随着抑郁症越来越被重视,抗抑郁的新药不断涌现。阿戈美拉汀(agometatine)作为第一个褪黑激素类抗抑郁药,由法国某公司研发,属于萘环类化合物,能同时激动MT1和MT2受体,且兼有拮抗5HT2C受体作用,可调节睡眠觉醒周期,调节患者的睡眠结构增加睡眠[1]。本研究主要对阿戈美拉汀原料药进行长期毒性研究,观察该药物对实验动物所产生的毒性反应、毒性靶器官及恢复情况,为临床安全用药提供参考。     

阿戈美拉汀与艾司西酞普兰治疗抑郁症有效性与安全性的对照研究

目的：对照分析阿戈美拉汀和艾司西酞普兰治疗抑郁症的临床效果及安全性,为临床治疗提供参考。方法：选取四川省南充精神卫生中心2016年6月至2018年6月期间所收治的150例抑郁症患者作为研究对象,随机分为2组,每组75例,对照组予以艾司西酞普兰治疗,研究组予以阿戈美拉汀治疗,治疗前和每个疗程结束后通过汉密尔顿抑郁量表（HAMD）对治疗效果进行评价,并通过不良反应量表（TESS）对药物不良反应（ADR）进行评价。结果：治疗前2组HAMD评分无显著性差异（P>0.05）,治疗后2组患者HAMD评分较治疗前均有显著改善（P<0.01）;治疗2周末研究组HAMD总评分明显低于对照组（P<0.05）,治疗4周及8周末2组患者的HAMD总评分无明显差异（P>0.05）;治疗期间,实验组TESS评分显著低于对照组（P<0.05）。结论：阿戈美拉汀治疗抑郁症的总显效率与艾司西酞普兰相当,但阿戈美拉汀起效更快、不良反应少,改善睡眠障碍效果更好,是一种安全、有效的抗抑郁药。     

Is the mGlu5 receptor a possible target for new antidepressant drugs?

The current treatment of depression, based on conventional antidepressant drugs that influence monoaminergic systems, is not satisfactory, and innovative antidepressant drugs are still needed. The next generation of treatments needs to be more effective, fasteracting and better tolerated than currently used antidepressants. Agrowing body of evidence indicates that compounds that modulate the glutamatergic system may be a group of novel and mechanistically distinct agents for the treatment of depression. Both preclinical and clinical data show strong, rapid and sustained effects of the NMDA receptor antagonist ketamine in treatment-resistant depression. However, ketamine cannot be considered as a novel antidepressant drug because of its side-effects and abuse potential. Because glutamatergic transmission is controlled not only by ionotropic but also by metabotropic glutamate receptors, their involvement in the etiology and the therapy of depression has also been postulated. Here, we review data supporting the potential antidepressant activity of mGlu5 receptor antagonists as well as the involvement of mGlu5 receptors in the pathophysiology of depression.     

Depression: emerging research and treatment approaches. 16-17 January 2003, Paris,France

In contrast to the more conventional meeting structure of describing the progress from molecule to man, this meeting began by illustrating the breadth of the problem of unipolar depression. Several speakers presented data indicating that unipolar depression is now the leading cause of disability-adjusted life years(DALY) in the world. Following several presentations regarding the recent advances in understanding the pathology of depression, the progress of antidepressant therapy over the last half-century was reviewed. The difficulties encountered in demonstrating the antidepressant activity of new compounds was analyzed, as was the way in which the signal-to-noise ratio might be improved in clinical trials. New antidepressant drugs, which are expected to enter the market in the near future, were represented by the pentapeptide nemifitide (Innapharma Inc) and the 5-HT 1B, receptor antagonist AR-A2 (AstraZeneca plc). The more distant future was envisaged by discussion of the problems and promises of genomic techniques in the discovery of new drug targets.     

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.     

常用抗抑郁药的疗效与安全性

由于社会发展迅速、生活节奏加快以及竞争日益激烈,人们的精神压力加大,导致抑郁症的发病率、患病率逐年增加.随着抗抑郁药物作用机制假说的不断提出,开发了一系列新型抗抑郁药物并应用于临床.本文就临床常见的新型抗抑郁药进行综述.     

Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics

Over the past several years, research has indicated that an individual's genetic makeup strongly influences not only their likelihood of developing depression, but also whether or not they will respond well to a particular antidepressant treatment. Identifying those genes regulating susceptibility to depression will increase our understanding of disease pathophysiology and direct the development of treatments that correct underlying neurobiological pathology related to stress-related psychiatric illnesses. Pharmacologically, the identification of genes regulating treatment response can lead to the design of novel pharmacological treatments and allow for more individualized, rational and successful drug treatments. Unfortunately, complex environmental and genetic mechanisms at play in depression and drug response make the discovery of susceptibility genes in humans quite difficult. Animal models may provide a more desirable system in which to discover susceptibility genes because environmental factors and tests can be regulated and more informative genetic methods can be used. Furthermore, a unique genetic opportunity exists with animal models of depression and antidepressant response because several rodent strains have been identified, or selectively bred, that display exaggerated depressive phenotypes on stress-related behavioral tests or divergent responses to antidepressant drugs. This paper reviews several of these rodent strains and illustrates the genetic strategies available to discover the long-sought susceptibility genes regulating these phenotypes.     

Recent progress in pharmacological and non-pharmacological treatment options of major depression

In spite of recent progress in the pharmacotherapy of depression major issues are still unresolved. These include the non-response rate of approximately 30% to conventional antidepressant pharmacotherapy, side effects of available antidepressants and the latency of several weeks until clinical improvement. The only non-pharmacological biological treatment options available so far which exert more rapid antidepressant efficacy are electroconvulsive therapy and, as an augmentation strategy, sleep deprivation. Current pharmacological treatments aim to enhance serotonergic and/or noradrenergic neurotransmission. In spite of emerging knowledge, the crucial mechanisms underlying both non-pharmacological treatments, which are responsible for antidepressant efficacy, are not yet clear so far. In the meantime several new pharmacological principles are under investigation with regard to their putative antidepressant potency. These include 5-HT1A receptor agonists, tachykinin receptor antagonists and various interventions within the hypothalamic-pituitary-adrenal system. While there is evidence for antidepressant properties of these new treatments in animal studies, in case series, in open studies and to some degree also in placebo controlled studies, no definite proof for the antidepressant efficacy of these new pharmacological strategies according to the requirements for evaluation of antidepressant drugs has been furnished so far. In contrast, for the established non-pharmacological treatment strategies including bright light therapy the clinical efficacy has been proven at least in subgroups of depression, but more knowledge of the main mechanisms underlying their antidepressant efficacy is still necessary. In addition new non-pharmacological treatments like repetitive transcranial magnetic stimulation, magnetic seizure therapy and Vagus nerve stimulation are currently under development. Nevertheless, a follow-up of both the new pharmacological strategies and non-pharmacological treatment options is of major importance to provide even better strategies for the clinical management of depression, which also is of great socio-economic impact.     

Strategies for the rapid treatment of depression

The purpose of this article is to review current literature relating to the determination of the time course of antidepressant effects. Further, this work explores studies examining the safety and effectiveness of pharmacological techniques for accelerating the therapeutic effects of antidepressant medication. A review of the literature pertaining to strategies for accelerating antidepressant medication effects was accomplished using the MEDLINE database, employing the key title words, antidepressant, rapid, and accelerating. A preponderance of evidence suggests that there is a multiple week latency for the onset of action of antidepressant medications. This latency appears to apply to virtually all standard antidepressants and may reflect slow adaptive changes to the inciting event of increased monoamine levels. Several strategies have received attention as potential strategies with which to accelerate the therapeutic effects of antidepressant medications. These include the use of high initial doses of some agents and also the use of initial augmentation strategies. Specifically, studies exist suggesting the acceleration of antidepressant effects using high initial doses of tricyclic antidepressants or venlafaxine, as well as the potential for acceleration by using initial augmentation with psychostimulants, lithium, or pindolol. Considering the morbidity and mortality associated with severe depression, a critical need exist for the exploration of ways in which to achieve antidepressant effects more quickly. A number of preliminary studies suggest strategies for the rapid treatment of depression, each with an apparent high degree of safety. Further investigations in more carefully defined patient populations and utilizing advances in the techniques for assessing antidepressant onset are needed. Copyright 2001 John Wiley & Sons, Ltd.     

抑郁症临床用药分析

目的：了解抑郁发作、双相障碍(抑郁相)患者的抗抑郁药应用和联合并用药等情况。方法：采用CCMD-3，对我院诊断为“抑郁发作、双相障碍(抑郁相)”患者共518例，按照住院年度分为5组，对每组患者临床应用的抗抑郁药和联合用药情况进行归类分析。结果：抑郁发作和双相障碍(抑郁相)的患者使用抗抑郁药的种类和比例均逐年变化，第一代抗抑郁药使用频度逐年下降，第二代抗抑郁药逐年上升，在使用种类和使用频度方面都有较大变化；合并苯二氮卓类药物较普遍，占40.15％。结论：抗抑郁药临床应用基本合理，第二代抗抑郁药临床应用逐年增加而合并苯二氮卓类药物比例偏高。     

Getting better, getting well: understanding and managing partial and non-response to pharmacological treatment of non-psychotic major depression in old age

In general, the pharmacological treatment of non-psychotic major depressive disorder in old age is only partially successful, with only approximately 50% of older depressed adults improving with initial antidepressant monotherapy. Many factors may predict a more difficult-to-treat depression, including coexisting anxiety, low self-esteem, poor sleep and a high coexisting medical burden. Being aware of these and other predictors of a difficult-to-treat depression gives the clinician more reasonable expectations about a patient's likely treatment course. If an initial antidepressant trial fails, the clinician has two pharmacological options: switch or augment/combine antidepressant therapies. About 50% of patients who do not improve after initial antidepressant therapy will respond to either strategy. Switching has several advantages including fewer adverse effects, improved treatment adherence and reduced expense. However, as a general guideline, if patients are partial responders at 6 weeks, they will likely be full responders by 12 weeks. Thus, changing medication is not indicated in this context. However, if patients are partial responders at 12 weeks, switching to a new agent is advised. If the clinician treats vigorously and if the patient and clinician persevere, up to 90% of older depressed patients will respond to pharmacological treatment. Furthermore, electroconvulsive therapy is a safe and effective non-pharmacological strategy for non-psychotic major depression that fails to respond to pharmacotherapy. Getting well and staying well is the goal; thus, clinicians should treat to remission, not merely to response. Subsequently, maintenance treatment with the same regimen that has been successful in relieving the depression strongly improves the patient's chances of remaining depression free.     

Mild depression in general practice: time for a rethink?

Clinical studies, conducted chiefly in hospital settings, have demonstrated that antidepressant drug therapy is effective treatment for major depressive disorder of at least moderate severity, and that cognitive therapy is an effective alternative to antidepressants in mild to moderate major depression. However, few clinical trials have taken place in general practice, where the great majority of patients with depression are managed. Most such patients in this setting do not meet diagnostic criteria for major depression, and are often described more loosely as having 'mild depression'. Many are given an antidepressant, often as the first step in treatment. Here, we consider whether this is the optimal approach for adults with mild depression in general practice.