脑源性神经营养因子在抑郁症发生和治疗中的研究进展

目前临床常用的抗抑郁药主要通过增加脑内突触间隙单胺类递质的浓度、增强单胺类神经的功能而起效,但这一机制不能很好地解释抗抑郁药存在的起效时间长等现象.近年提出,抗抑郁药可能还通过增加海马区域脑源性神经营养因子(BDNF)基因表达起效.抗抑郁药能增加受试动物海马区BDNF基因表达,抑郁患者接受抗抑郁药治疗,其血清BDNF水平上升;BDNF基因的单核苷酸多态性也与抑郁症的发生有关;抗抑郁药可能还通过激活丝裂原活化蛋白激酶(MAPK)信号通路,磷酸化cAMP反应序列结合(cREB)蛋白,最终使BDNF基因表达上调.这一机制的提出为抑郁症生物学病因的阐明提供了必要信息,同时也有助于抗抑郁新药的开发,为研制安全、有效的新药提供新的思路.     

选择性5-羟色胺再摄取抑制剂类药物的研究进展

选择性5-羟色胺再摄取抑制剂(SSRIs)类药物始用于20世纪80年代,因其具有对5-羟色胺(5-HT)选择性高,对其他递质影响小,尤其对心血管系统和胆碱能作用较少,而半衰期普遍较长,患者依从性较好等优点,逐渐受到医患青睐,成为目前治疗抑郁症的一线药物,在临床上使用最为广泛,已占据世界抗抑郁药市场一半以上的份额。截至2008年底有8种畅销抗抑郁药销售额合计超过全球抗抑郁药市场的80%,而SSRIs类药物包揽了前4名。然而,我国的抗抑郁药市场长期以来发展速度较为缓慢。为尽快提升我国抑郁症人群治疗水平,充分开发抗抑郁药物市场,对SSRIs类药物的研究进展进行综述,以期为临床医师提供更详尽的、前沿的一手资料,从而更好地满足广大患者的临床需要。     

抑郁症治疗靶标及其药物研发进展

抑郁症的发病机制至今仍未完全阐明。传统的抗抑郁药是基于单胺递质假说而开发的。近年来,除了单胺类外,谷氨酸系统、HPA轴等一些新的抑郁症治疗靶标逐渐成为研究热点,基于这些靶标研发的新型抗抑郁药已取得重大进展,本文就抑郁症的治疗靶标和新药研发情况作一综述,为临床治疗和开发新药提供参考。     

新型抗抑郁药万拉法辛的临床应用

20世纪60年代第一个三环类抗抑郁药 (TCAs)丙咪嗪被证明有抗抑郁效应,相继出现多种此类药物,使许多抑郁症病人症状获得缓解.但是由于应用过程中的一些缺陷,一些病人并未得到较好的效果,有的甚至放弃治疗.近年来抗抑郁新药的研制迅速发展,开发了第二代抗抑郁药.     

抑郁动物模型的研究进展及评价

<正>世界卫生组织预测到2020年抑郁症(MDD)将会成为世界第一大疾病负担[1]。尽管单胺类抗抑郁药彻底改变了抑郁症治疗,但目前的抗抑郁药仍然没有符合预期标准。相当大比例的患者使用一线抗抑郁药治疗效果不佳[2]。对于使用一线抗抑郁药有效的患者,往往需要几周甚至几个月才出现效果。因此,目前迫切需要新的作用机制和更短起效时间的有效抗抑郁药。尽管目前有一些抑郁症模型,但没有一个能完全包括抑郁症的所有特点。此外,许     

老年抑郁症药物治疗进展

简述近年临床对老年抑郁症的认识，重点介绍抗抑郁药物机制、研究进展和药物筛选思路，分类介绍近年开发的代表性抗抑郁药物，讨论老年抑郁症治疗和对抗抑郁药物性能的要求。以期引起对老年抑郁症的共识和重视。     

米氮平口腔崩解片治疗抑郁症患者的临床研究概述

除了研发新药以外,现有药物新剂型的研发和应用也是治疗抑郁症的新思路。口崩剂型抗抑郁药米氮平口腔崩解片凭借其便于携带、口感良好及易于吞服等优点,作为能较好改善抑郁症患者依从性的一种剂型在临床广泛应用。本文从疾病本身的特点,结合抗抑郁药物的药理特征和不良反应,介绍米氮平口腔崩解片在抑郁症患者的临床研究情况。     

三唑仑与氟西汀合用的药动学评价

化学结构与三环和四环类无关的抗抑郁药氟西汀(Fluoxetine)已在美国认可用于治疗成人抑郁症。接受抗抑郁药如氟西汀治疗的患者可能出现失眠症状。这可能是精神疾患(如抑郁症)原有的症状或药物潜在的副作用,因而需用催眠药作短期治疗。广泛用于临床的苯二氮类催眠药三唑仑(Triazolam),     

抗抑郁药物新进展

抑郁症是一种常见的精神疾病,属情感性障碍.随着生活节奏不断加快,人们的精神压力也逐渐增大,抑郁症已成为现代社会的常见病、高发病,其发病率正在快速攀升.据不完全统计,目前全世界抑郁症患者已占世界人口的3%～5%.通过药物治疗,其中约2/3的患者可取得不同疗效.高发且难以根治的抑郁症使得抗抑郁药市场具有广阔的前景,这正是近年来国外热衷于抗抑郁药物研究与开发的主要原因之一[1].笔者将对各种抗抑郁药物的进展作一综述.     

中枢神经系统药物新制剂

抑郁症是最常见的精神疾病，全球约有1．2亿人罹患此病。WHO预测至2020年抑郁证将是导致伤残的主要原因。从2005年6月由中华医学会精神病学分会主办的亚洲精神科学高峰会（APNS）上获悉：目前中国抑郁症患者超过2600万，但只有不到10％的患者接受了相关的药物治疗。抑郁症带给中国的总经济负担达到622亿元人民币。抗抑郁药销售额占中枢神经系统药物市场最大的份额，2004年全球销售额为159亿美元，据预测2011年会下降至135亿美元。     

聚焦糖尿病治疗药物

糖尿病药物市场是当前制药行业最具价值和发展最快的市场之一,拥有大量需要药物干预的糖尿病患者。自从胰岛素被发现以来,制药公司研发了一大批具有数十亿美元销售额的药物。由于人们更倾向于久坐的生活习惯,世界卫生组织预测糖尿病患者数量将呈爆炸性增加,也极大地提高了大批新型重磅炸弹级抗糖尿病药物问世的几率。在新型药物（包括传统的胰岛素类似物）稳固地位的驱动下,糖尿病药物市场被预测将在未来5年内翻倍。本综述分析了当前市场动态,以及越来越不利于市场发展的管理环境对产品发展的影响。当创新药物面临着国家监管部门越来越多的审查,胰岛素类生物仿制药的法规也即将颁布,从长远来看,将在无形中削弱糖尿病市场。此外,还讨论了胰岛素仿制药进入市场带来的重要挑战,并对其治疗作用进行了评价。     

Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs

The birth of new neurons, or neurogenesis, in the hippocampal formation has been demonstrated throughout the lifetime of multiple species including humans. A major finding in the field of depression is that treatment with antidepressant drugs increases hippocampal neurogenesis. This review presents a current summary of this field of study and presents the hypothesis that increasing adult hippocampal neurogenesis may be a new drug target or mechanism for future antidepressant drugs. It has been demonstrated that multiple classes of antidepressant drugs increase hippocampal cell proliferation and neurogenesis in a chronic and not acute time course, which corresponds to the therapeutic time course necessary for effects. Conversely, animal models of depression or stress paradigms decrease cell proliferation. Clinically, there is evidence of reduced hippocampal volume in patients with major depressive disorder or other affective disorders. Taken together, this data indicates that reduced hippocampal cell number may be involved in the pathophysiology of depression and reversal of this may be one way the antidepressant drugs exert their effects. We hypothesize that the next generation of antidepressant drugs will, in addition to their effects on known transmitter or second messenger systems, involve either direct or indirect targeting of neurogenic factors. In addition, the ability of novel compounds to be tested for the neurogenic potential may become an additional way to evaluate a compound for putative antidepressant effects.     

Fibromyalgia syndrome: an overview of potential drug targets

Fibromyalgia syndrome (FMS) is a chronic disease of widespread and debilitating pain. The cause of FMS is unknown and its risk factors are poorly understood. It occurs frequently in the general population where it is often co-morbid with other rheumatoid and pain disorders, and psychiatric disorders such as anxiety and depression, making diagnosis particularly difficult. Several types of drugs are used to treat FMS, but none are specifically approved for this indication. FMS appears to be strongly associated with depression or at least with some symptoms of depression, and antidepressants appear to be effective in the treatment of this disorder. The advent of new classes of antidepressants with fewer side effects than older drugs has suggested new avenues of therapy for patients diagnosed with FMS.     

Paroxetine treatment of depression in late life

The elderly population is growing at a rapid rate and currently constitutes more than 12% of the United States' population. Within the next 30 years, the number of elderly persons is expected to more than double, creating a concerning situation regarding provision of healthcare services. Depression is a prevalent and underrecognized disorder in older adults and is associated with both increased healthcare utilization and suicide. Treatment of depression improves quality of life and reduces functional decline and suicidal ideation. Maintenance therapy for depression is commonly overlooked and must be emphasized for management of depression in elderly patients. First-line treatment options include selective serotonin reuptake inhibitors (SSRIs), one of which, paroxetine, has been studied extensively in older adults. The findings of studies that have evaluated the efficacy of paroxetine demonstrate successful treatment of depression and long-term relapse prevention in this population. With the significant personal and societal burden that is associated with major depression in the elderly, appropriate treatment is important and must be incorporated into standard practices by healthcare professionals.     

Sertraline. A pharmacoeconomic evaluation of its use in depression

Depression is a common condition that is often unrecognised, misdiagnosed and/or undertreated. It is associated with substantial direct, indirect and intangible costs. The indirect costs of lost earnings/productivity and premature death account for the majority of these costs; drug costs account for only about 1 to 2% of total costs and about 10 to 12% of direct costs. Thus, better recognition and appropriate treatment of depression would increase the direct costs associated with this illness, but would also have the potential to greatly reduce indirect costs and consequently the overall cost of depression. Because of their higher acquisition costs relative to tricyclic antidepressants (TCAs), there has been much debate about whether the use of sertraline or other selective serotonin reuptake inhibitors (SSRIs) for first-line treatment of depression can be justified. While these agents have similar efficacy to TCAs, they are better tolerated and have a lower risk of death on overdosage. Despite the large economic burden of depression on society, pharmacoeconomic data on sertraline and antidepressant drugs in general are scarce. Most of the available studies on sertraline are limited to considerations of direct costs and do not assess costs from a societal perspective. In addition, a number of studies have significant methodological problems which limit determination of meaningful conclusions. Nonetheless, data from 2 more recent studies with fewer methodological problems than earlier studies indicated that sertraline was more cost-effective than TCAs because of fewer psychiatrist consultations, and less costly than fluoxetine because of fewer absences from work and fewer medical consultations. The cost-utility ratio of maintenance therapy of depression with sertraline appears to fall within the range of accepted cost-utility ratios of common healthcare interventions. Thus, studies to date have generally shown that overall treatment costs with sertraline and other SSRIs are no greater than those for TCAs; this is despite the lower acquisition costs of the latter agents. Therefore, it is clear from these data that it is misleading to classify antidepressant agents as expensive or inexpensive based solely on their acquisition costs. Sertraline, therefore, can be considered as a first-line alternative to TCAs and other SSRIs for the treatment of depression on both clinical and pharmacoeconomic grounds.     

Transdermal Route: A Viable Option for Systemic Delivery of Antidepressants

The high rise in the population suffering from depression depicts the need for improved and highly effective treatment options for this condition. Efforts to develop existing drugs into user-friendly dosage forms with a number of advantages in major depressive states, including but not limited to: sustained drug release, reduced drug dosing frequency, improved tolerance and adherence, suitability for use in diverse populations and different treatment scenarios, as well as less central nervous system side effects are required. One such non-invasive drug delivery route that could provide the aforementioned benefits in the treatment of depression is the transdermal route. A number of conventional and emerging transdermal delivery strategies have been investigated for some potent antidepressants and results depict the potential of this route as a viable means for systemic delivery of therapeutically relevant doses of the tested agents, with Emsam®, the commercially available patch of selegiline, being an evidence for the same. The investigated approaches include the formulation of transdermal patches, use of vesicular drug carriers, pro-drug approach, microemulsification, chemical as well as physical enhancement technologies. This review provides a comprehensive account of the rationale, developments made till date, scope and future prospects of delivering antidepressants via the transdermal1 route of administration.     

Go with the flow - a review of the respiratory therapeutic area

This article recognises the present significance of respiratory disease as a finite number of conditions affecting over 5% of the developed world’s population and attracting a multitude of therapeutic responses. The global market is described in terms of present and future treatment options and their relative potential. The future prospects for emerging new drugs are affected by the prospects offered by a market approaching maturity. Blockbuster breakthroughs are unlikely to happen here. GlaxoSmithKline are expected to consolidate their dominant 30% market share in the medium term. Other contenders will not seriously challenge unless shrewd alliances and opportune development initiatives offer a radical treatment breakthrough. Oral compounds, genetic markers, new device technologies, safer steroids, new generation NSAIDs, cytokine/leukotrine-targeted compounds and vaccines are all fancied prospects for the longer term. It will be prohibitively expensive to back all such prospects, even for Glaxo. Focus is the only option. As for patients, the quality of life for the majority will continue to improve, without any shift in treatment protocols. Respiratory diseases are now well controlled, though prevention remains a distant prospect [1-7].     

Adapting problem-solving therapy for depressed older adults in methadone maintenance treatment

Late-life depression is prevalent in older adults who are dependent on opiates. Depressive disorders among opiate abusers have detrimental effects on their well-being and ability to refrain from illegal drugs. There are numerous barriers to the provision of appropriate mental health care to older adults receiving methadone maintenance treatment. This article focuses on problem-solving therapy (PST) and presents evidence that PST may be a promising nonpharmacological treatment for older methadone clients with comorbid depressive disorders that can be applied within the staffing and resource limits of methadone maintenance treatment facilities. The advantages of PST relative to other behavioral therapies for this population are based on evidence that PST is less cognitively demanding for an older adult population with mood and substance use disorders. A properly modified PST for an older adult substance-dependent population with subsyndromal or diagnosed depression may be a viable option for methadone maintenance programs with limited resources.     

人源肿瘤异种移植模型在罕见癌症中的应用进展

随着早期诊疗、靶向药物和免疫疗法的普遍应用,大部分常见癌症的5年生存率都有较明显的提升。相比于常见癌症,罕见癌症由于其发病率较低,长期缺乏足够的关注度。然而,基于庞大的人口总数,罕见癌症的发病数依然是不容忽视的,但有效治疗手段的缺失使得罕见癌症患者的预后不佳。罕见癌症的研究难点之一在于癌种群体分散,样本量较小,难以进行相关的临床研究。而患者来源的异种移植模型可有效保存患者样本,高度模拟原发肿瘤,是研究罕见癌症的有利工具。就罕见癌症的概念和人源肿瘤异种移植模型在不同类别的罕见癌症如腺样囊性癌、胆管癌、肛管癌、恶性间皮瘤、罕见妇科癌症、睾丸癌、黑色素瘤、恶性胚胎肿瘤、脊索瘤、胃肠胰神经内分泌肿瘤、肾上腺皮质癌、胶质母细胞瘤、血液系统恶性肿瘤中的应用进展进行综述,以期为探索罕见癌症发病机制及开发更具有前景的抗罕见癌症药物提供参考。     

Pharmacotherapy of dual substance abuse and dependence

The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug's original indication by the FDA. Such 'off-label' prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature.The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect.