Utrecht University, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Division of Pharmacology, Universiteitsweg, The Netherlands.
Expert Opin Investig Drugs. 2011 Aug;20(8):1107-30. doi: 10.1517/13543784.2011.594039. Epub 2011 Jun 20.
Major depression is one of the most prevalent forms of mental illnesses and is among the leading causes of disability, affecting about 121 million people worldwide. Approximately 30% of patients fail to respond to present therapies. Therefore, the search for novel antidepressant drugs continues.
The most prescribed antidepressants are serotonin reuptake inhibitors and/or noradrenaline reuptake inhibitors, which only indirectly affect dopaminergic neurotransmission. As a consequence, residual symptoms remain, including impaired motivation and impaired pleasure. This article reviews the development of new broad-spectrum antidepressants, the triple reuptake inhibitors, which also increase brain dopamine levels.
In this review, a distinction is made between the subtypes of melancholic and atypical depressions and their associated brain abnormalities and dysfunctions in neurotransmitter systems. Subsequently, we propose a hypothetical model: 'the monoamine hypothesis revisited' to predict what kind of pharmacological treatment will be effective in the different subtypes of depression. It is expected that the triple reuptake inhibitors, inhibiting the reuptake of all three monoamines, can produce a greater efficacy than traditional antidepressants especially in atypical depression. Since triple reuptake inhibitors may also dampen states of hyperglutamatergic activity and subsequent excitotoxicity, it is suggested that these new drugs have a considerable neuroprotective potential in major depression, especially in melancholic depression.
重度抑郁症是最常见的精神疾病之一，也是导致残疾的主要原因之一，全球约有 1.21 亿人受到影响。大约 30%的患者对现有疗法没有反应。因此，人们继续寻找新的抗抑郁药物。
最常开的抗抑郁药是血清素再摄取抑制剂和/或去甲肾上腺素再摄取抑制剂，它们只是间接影响多巴胺能神经传递。因此，仍然存在残留症状，包括动机受损和快感缺失。本文回顾了新的广谱抗抑郁药——三重再摄取抑制剂的发展，这种药物也能增加大脑中的多巴胺水平。
在这篇综述中，对忧郁症和非典型抑郁症的亚型及其相关的大脑异常和神经递质系统功能障碍进行了区分。随后，我们提出了一个假设模型：“重新审视单胺假说”，以预测哪种药物治疗在不同类型的抑郁症中会有效。预计三重再摄取抑制剂可同时抑制三种单胺的再摄取，其疗效可能优于传统的抗抑郁药，尤其是在非典型抑郁症中。由于三重再摄取抑制剂也可能抑制过度谷氨酸活性和随后的兴奋性毒性状态，因此建议这些新药在重度抑郁症中具有相当大的神经保护潜力，尤其是在忧郁性抑郁症中。
