불안장애의 새로운 치료제로서의 Agomelatine = Agomelatine as a Novel Pharmacotherapy of Anxiety Disorders

다국어 초록 (Multilingual Abstract)

Anxiety disorders are the most common mental health problems and frequently cause functional impairment. Although current pharmacological agents are recognized to be effective, partial or total resistance to drug treatment and distressing side effects have leaded to continued search of a new pharmacotherapy of anxiety disorders. Agomelatine is a novel agent with a melatonergic agonist at MT1 and MT2 receptors and an antagonist at 5HT2C receptors. Despite substantial evidence of its antidepressant properties, the anxiolytic properties of agomelatine have been underscored. Therefore, this article reviews previous studies on anxiolytic properties of agomelatine. In several rat models, agomelatine actively reduces anxiety-related behaviors comparable to benzodiazepine. These anxiolytic properties seem to be mediated by both melatonergic and 5HT2C receptors.
Randomized, double-blind, clinical trials demonstrated that agomelatine 25-50 mg/day significantly reduced anxiety symptoms in patients with generalized anxiety disorder as well as major depressive disorder. Recently, cases of panic disorder and social anxiety disorder successfully treated with agomelatine were reported. In addition, the tolerability of agomelatine seems broadly favorable, particularly in sexual dysfunction and discontinuation syndrome. Based on these sound efficacy and tolerability profiles, further studies on the use of agomelatine in anxiety disorders will be required for wider clinical application.

국문 초록 (Abstract)

불안장애는 매우 흔하고 상당한 기능장애를 동반한 질환으로 다양한 약물들이 치료에 사용되고 있지만, 그 효과와 부작용 측면에서 다소 한계가 있어 새로운 치료제의 개발에 대한요구가 있어왔다. agomelatine은 MT1 및 MT2의 작용제이며5-HT2C 수용체의 길항제라는 작용 기전을 가진 약물로, 임상연구들에서 항우울 효과가 입증된 데 비해서 항불안제로서의효과는 아직 충분히 연구되지 않았다. 이에 본 종설에서는 agomelatine의항불안 효과에 대한 근거가 되는 약리학적 기전, 동물연구 및 임상연구에서의 항불안 효과, 내약성에 대해서 고찰하였다.
agomelatine은 다양한 불안 관련 동물모델에서 불안을 의미 있게 감소시켰으며, 항불안 효과에는 멜라토닌 수용체와5-HT2C 수용체가 모두 관여하였다. 임상연구에서는 주요 우울장애와 관련된 불안증상 이외에도, 범불안장애 환자들을 대상으로 한 무작위, 이중맹검, 위약 대조 연구에서도 유의하게 주요 불안증상 및 동반된 신체불안, 불면을 호전시키고 일상생활 기능을 향상시켰다. 이 외에 치료저항성 사회불안증 환자및 성기능장애 등의 부작용으로 약물 비순응을 보이는 공황장애 환자들에서 유용한 대안으로 보고되었다. 항불안 효과에 있어 기존 치료제들과 동등하며 및 성기능장애와 중단증후군 증상을 비롯한 내약성 측면에서는 오히려 우수하여,agomelatine은 불안장애에서 기존 약물의 문제점을 극복할수 있는 하나의 대안으로의 가능성이 시사된다.
agomelatine의 항불안 효과를 확정하기 위해서는 불안장애에서의 향후 더 많은 연구와 임상경험이 필요할 것이다. 장기간 치료 및 추적 연구를 통해 관해 및 재발방지 효과를 규명하고, 장, 단기 부작용에 대한 더 많은 자료가 필요 하겠다.
아울러 우울 및 불안과 관련된 감정 처리 과정의 변화와 스트레스로 인해 유발된 신경가소성 감소를 개선시키는 등의 효과에 대한 결과들을 바탕으로 항불안 효과와 관련된 심리학적 및생물학적 기전에 대한 연구도 동반되어야 하겠다.

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