[转译]新一代快速起效的抗抑郁药物(New Generation of Rapid-Acting Antidepressants)

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ScienceDaily (Mar. 6, 2010) — Conventional antidepressant treatments generally require three to four weeks to become effective, thus the discovery of treatments with a more rapid onset is a major goal of biological psychiatry. The first drug found to produce rapid improvement in mood was the NMDA glutamate receptor antagonist, ketamine.

In a new issue of Biological Psychiatry, published by Elsevier, researchers from the National Institutes of Health report that another medication, scopolamine, also appears to produce replicable rapid improvement in mood. Scopolamine temporarily blocks the muscarinic cholinergic receptor, thought to be overactive in people suffering from depression.
Drs. Wayne Drevets and Maura Furey recruited outpatients with major depressive disorder who were randomly assigned to receive placebo and then scopolamine treatment, or vice versa, in a double-blinded design so that neither the researchers nor the patients knew which treatment they were receiving.
"Scopolamine was found to reduce symptoms of depression within three days of the first administration. In fact, participants reported that they experienced relief from their symptoms by the morning after the first administration of drug," explained Dr. Furey. "Moreover, one-half of participants experienced full symptom remission by the end of the treatment period. Finally, participants remained well during a subsequent placebo period, indicating that the antidepressant effects persist for at least two weeks in the absence of further treatment."
The efficacy of scopolamine is very interesting because the potent blockade of muscarinic receptors was a property of tricyclic antidepressant medications, the oldest type of antidepressants. With these medications, the muscarinic receptor blockade was mostly viewed as the cause of unwanted side effects, such as constipation, sedation, and memory impairments. Newer antidepressants, such as serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, were explicitly designed to avoid blocking muscarinic receptors. Yet, the current data raise the possibility that this strategy may have increased safety and tolerability of these medications at the expense of providing effective and timely relief for depression symptoms.
Dr. John Krystal, Editor of Biological Psychiatry, commented that these findings "have the potential to raise expectations for new antidepressant treatments. Three-to-six weeks is a long time to wait for depression symptoms to be alleviated. Depressed people describe their emotional state using terms like 'agony' and others compare their condition to 'living in hell'. Further, depression is a life-threatening condition for some, preventing them from performing basic self-care functions or causing them to exhibit self-destructive behavior."
Although these findings open the door to a conceptually different approach to the treatment of depression, it remains to be seen whether rapid acting antidepressant effects will be viable clinically. One could imagine that they might mitigate hospitalization in some patients and enhance the overall effectiveness of the treatment of depression. However, this possibility remains to be demonstrated empirically in studies that show that a rapid-acting antidepressant treatment can be smoothly transitioned to definitive long-term treatment for depression.

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每日科学“（2010年3月6日，） - 传统的抗抑郁药治疗，一般需要三到四个星期才能生效，因此，生物精神病学的一个主要目标就是寻找一种更快速起效的治疗方式。已经发现的第一个能够迅速改善情绪的药物是ketamine（氯胺酮）- NMDA谷氨酸受体拮抗剂，。

新一期的《生物精神病学》杂志，由Elsevier出版，刊登了美国国立卫生研究院的研究人员的一项研究，另一种药物，Scopolamine（东莨菪碱），显示也产生可重复的情绪的迅速改善。Scopolamine暂时阻断毒蕈碱胆碱受体，该受体被认为在患抑郁症的人群中过于活跃。
  Wayne Drevets 博士和Maura Furey招募了一批重性抑郁症门诊患者，他们设计了双盲测试，随机分配这些人接受安慰剂和Scopolamine的治疗。无论研究人员还是病人都不知道他们正在接受哪一种治疗。
测试发现，在第一次指导患者进行治疗的头三天，Scopolamine减少了抑郁症的症状。事实上，患者报告在他们第一次接受指导进行服用Scopolamine的早上，便有了抑郁症装减轻的体验。 Maura Furey博士解释说“此外，有一半的参与者在治疗阶段结束后，感觉到抑郁症状完全缓解。最后，治疗结束后会给予参与者一段时间的安慰剂治疗，在这段时间内，患者仍然感觉良好。这表明，在没有抗抑郁药的情况下，Scopolamine的抗抑郁效果至少可以持续两个星期。”
Scopolamine疗效非常有趣，因为有力的毒蕈碱受体的阻断是一种三环类抗抑郁药物的特性，最古老的类型的抗抑郁药。这些药物，毒蕈碱受体阻断大多被视为有害的副作用，如便秘，镇静，记忆障碍，事业。较新的抗抑郁药，如5-羟色胺再摄取抑制剂或5-羟色胺-去甲肾上腺素再摄取抑制剂，便是有意设计成避免阻断毒蕈碱受体。然而，当前的数据增加这种可能性，这种策略可能增加了这些药物的安全性和耐受的可能性，但是却已牺牲提供有效和即时的抑郁症状的减轻为代价。
约翰克里斯塔尔博士，生物精神病学的编辑，评论说，这些研究结果”有可能增加人们对新的抗抑郁药治疗的预期。抑郁症症状得到缓解需要等待三至6个星期，这是很长一段时间。患抑郁症用“痛苦”和其他词语来描述自己的情绪状态，并且用“生活在地狱”来比较自己的生存现状。此外，抑郁症对于一些人来说是危及生命的疾病，它会阻碍他们执行基本的自我照顾能力，或使使他们他们有倾向于自我毁灭的行为。“  “
虽然这些发现开启一道大门，人们可以从一个完全不同的概念和方法上来治疗抑郁症，我们仍然有待观察这种速效抗抑郁作用是否将是临床可行的。人们可以想像，它可能会减少部分患者住院的可能性和提高治疗抑郁症的整体效果。但是经验研究表明，一个快速起效的抗抑郁药治疗顺利过渡到明确的长期抑郁症治疗，仍然是有可能的。

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2# freeinterface 我这里还有一些ketamine的英文介绍，我会随后将英文和翻译的中文放上去，希望大家可以一起讨论讨论。我觉得关于抗抑郁药物方面的研究，国外的进展还是非常快的。快速起效的抗抑郁药物的出现的希望，使我们可以大胆一点的预期，在不是太遥远的未来，抑郁症真的可以变成像“感冒”这样的普通疾病，得病了，去医院打几针，就可以迅速的缓解症状，从而尽量减少对工作和生活的影响。

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3# freeinterface ketamine据说可以在一次注射后，在数小时内起效，是迄今知道的起效最迅速的化学物质。