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새로운 우울증 치료 약물

Novel Pharmacological Treatment for Depression

문은수|정희정
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2016.02|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제23권 제1호|pp. 1-11

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참고문헌

키워드

우울장애약물치료PharmacotherapyDepressive disorderTreatment-resistant depression치료저항성 우울증새로운 항우울제Novel antidepressant
주제분류정신과학

초록

모노아민 산화효소 억제제(monoamine oxidase inhibitor, 이하 MAO 억제제)와 삼환계 항우울제(tricyclic antidepressant, 이하 TCA) 계열의 항우울제들이 개발되면서 우울증의 약물치료 시대가 열렸다.1) 그 뒤를 이어 선택적 세로토닌 재흡수 억제제(selective serotonin reuptake inhibitor, 이하 SSRI)와 세로토닌 노르에피네프린 재흡수 억제제(serotonin norepinephrine reuptake inhibitor, SNRI), 도파민노르에피네프린 재흡수 억제제(dopamine norepinephrine reuptake inhibitor, DNRI), 노르아드레날린-세로토닌계 항우울제(noradrenergic and specific serotonergic antidepressant, NaSSA) 계열의 항우울제들이 개발되면서 MAO 억제제와 TCA 계열의 항우울제와 유사한 치료효과를 지니면서도 부작용이 많이 감소하여 우울증의 약물치료가 한층 발전하게 되었다.2)3) 하지만, 이러한 약물들을 단독요법 또는 병합요법으로 충분히 사용하더라도 치료가 되지 않는 치료 저항성 우울증이 여전히 존재하고 있다.4)5) 치료 저항성 우울증을 극복하기 위해 갑상선 호르몬이나양극성장애에서 사용하는 항정신병약물과 기분조절제를 우울증 치료에 이용함으로써 치료 저항성 우울증의 치료반응을 조금 더 높이기는 하였지만, 그 역시 한계가 있다.6) 항정신병약물과 기분조절제의 장기 사용에 따른 부작용의 발생 위험성이 문제가 될 수 있고, 이러한 약물을 사용하더라도 여전히 우울증상이 관해에 이르지 못하는 경우가 있다.7) 뿐만아니라, 현재까지 개발된 항우울제는 치료효과가 발생하기까 지 수주에서 수개월의 시간이 걸리는 측면도 우울증 환자를고통스럽게 하는 요소가 되고 있다.8)9) 따라서 이러한 우울증치료의 한계점들을 극복하기 위한 노력이 중요하다. 최근에는 세로토닌 수용체 길항제나 멜라토닌 길항제가 개발되어치료에 이용되고 있다.10)11) 이러한 항우울제들은 우울증 치료방법을 보다 다양하게 한 측면들이 있다는 점에서 관심을 받고 있지만, 우울증 치료의 한계점들을 충분히 해결하지는 못하고 있는 현실이다.12) 그동안 우울증의 병태생리나 항우울제의 기전을 밝히기위한 많은 연구들이 진행되어 왔다.13)14) 그러나 아직까지도우울증의 병태생리와 항우울제의 기전에 대해서 모든 부분들이 명확하게 밝혀져 있지는 않다. 하지만, 지금까지 알려진생물학적인 기전을 응용하여 새로운 항우울제를 개발하기 위한 시도들이 계속 이어지고 있다.14)15) 이러한 시도들이 항우울제의 개발로 모두 이어지는 것은 아니겠지만, 우울증 치료의한계점들을 극복하기 위한 현재의 노력들이 어떻게 진행되고있는지를 이해하는 것은 미래의 우울증 치료를 부분적으로나마 예측하는 데 도움이 될 수 있다. 따라서 본 논문에서는잠재적인 항우울제로 관심을 받고 있는 뇌염증반응(neuroinflammation) 조절제, 산화적 스트레스(oxidative stress) 조절제, 항콜린성 약물, 시상하부-뇌하수체-부신 축(Hypothalamic Pituitary Adrenal Axis, 이하 HPA 축) 조절제, 글루타메이트(glutamate) 조절제, opioid 조절제, substance P, neuropeptide Y, galanin과 같은 신경펩타이드(neuropeptide) 조절제에 대한 내용들을 소개하고자 한다.

Abstract

Development of various antidepressants such as monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressant has led to a tremendous progression of pharmaceutical treatment for depression, but still there are some limitations of current antidepressants, such as treatment- resistant depression and delayed onset of antidepressants. The pathogenesis of depression is unclear because depression is a heterogeneous disease state, and the mechanisms of antidepressants remain uncertain as well. Nevertheless, in an attempt to develop novel antidepressants, some trials have been conducted based on the potential biological mechanism discovered in the numerous research results. This review will provide information about the potential novel antidepressants and the current states of clinical studies using them. In particular, some potential novel antidepressants anti-inflammatory agents, antioxidants, anticholinergics, modulators of Hypothalamic Pituitary Adrenal Axis, glutamate, and opioid systems, as well as some neuropeptides such as susbstance P, neuropeptide Y, and galanin will be discussed.

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