无血性
临床终点
医学
临床试验
预测(人工智能)
心理学
腹侧纹状体
随机对照试验
精神科
萧条(经济学)
内科学
安慰剂
纹状体
精神分裂症(面向对象编程)
多巴胺
经济
替代医学
人工智能
病理
宏观经济学
计算机科学
作者
Sara Costi,Laurel S. Morris,Katherine A. Kirkwood,Megan Hoch,Morgan Corniquel,Brittany Vo-Le,Tabish Iqbal,Nisha Chadha,Diego A. Pizzagalli,Alexis E. Whitton,Laura Bevilacqua,Madhukar H. Trivedi,Stefan Ursu,Alan C. Swann,Katherine A. Collins,Ramiro Salas,Emilia Bagiella,Michael K. Parides,Emily Stern,Dan V. Iosifescu,Ming-Hu Han,Sanjay J. Mathew,James W. Murrough
标识
DOI:10.1176/appi.ajp.2020.20050653
摘要
Preclinical studies point to the KCNQ2/3 potassium channel as a novel target for the treatment of depression and anhedonia, a reduced ability to experience pleasure. The authors conducted the first randomized placebo-controlled trial testing the effect of the KCNQ2/3 positive modulator ezogabine on reward circuit activity and clinical outcomes in patients with depression.Depressed individuals (N=45) with elevated levels of anhedonia were assigned to a 5-week treatment period with ezogabine (900 mg/day; N=21) or placebo (N=24). Participants underwent functional MRI during a reward flanker task at baseline and following treatment. Clinical measures of depression and anhedonia were collected at weekly visits. The primary endpoint was the change from baseline to week 5 in ventral striatum activation during reward anticipation. Secondary endpoints included depression and anhedonia severity as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Snaith-Hamilton Pleasure Scale (SHAPS), respectively.The study did not meet its primary neuroimaging endpoint. Participants in the ezogabine group showed a numerical increase in ventral striatum response to reward anticipation following treatment compared with participants in the placebo group from baseline to week 5. Compared with placebo, ezogabine was associated with a significantly larger improvement in MADRS and SHAPS scores and other clinical endpoints. Ezogabine was well tolerated, and no serious adverse events occurred.The study did not meet its primary neuroimaging endpoint, although the effect of treatment was significant on several secondary clinical endpoints. In aggregate, the findings may suggest that future studies of the KCNQ2/3 channel as a novel treatment target for depression and anhedonia are warranted.
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