Double-blind pilot trial of mirtazapine for the treatment of co-occurring AD/MDD

描述(由申请人提供)：本提案是针对PA-10-252题为“共现酒精使用障碍和抑郁/焦虑障碍的治疗(R21)”而写的。酒精依赖(AD)和严重抑郁障碍(MDD)是普通人群中最常见的精神障碍之一，这两种疾病的并存代表着一个重大的公共卫生问题。研究表明，在共病人群中，酒精使用水平与抑郁症状水平有关。以前在这一并存人群中使用SSRI抗抑郁药进行的药物试验结果令人失望。米氮平是一种非SSRI类药物，具有独特的结构和作用机制。最近的研究结果表明，米氮平可能比其他抗抑郁药更有效、更快起效。我们自己最近的开放标签初步研究表明，米氮平在减少AD/MDD受试者的饮酒和抑郁症状方面具有强大的组内疗效。然而，在这项研究中没有使用安慰剂对照组，因此无法评估组间疗效与安慰剂的效果。目前的赠款申请建议进行第一项双盲、安慰剂对照的试点研究，以初步评估米氮平与安慰剂在减少AD/MDD共病患者的酒精使用和抑郁症状方面的疗效。如果这项拟议的双盲试点研究的结果是有希望的，那么在这项拟议研究中发现的效应大小将被用于 帮助设计一项动力充足的R01治疗试验，以明确测试米氮平与安慰剂在这一并存人群中的疗效。

DESCRIPTION (provided by applicant): This proposal is written in response to PA-10-252 entitled, "Treatment of Co-Occurring Alcohol Use Disorders and Depression/Anxiety Disorders (R21)". Alcohol dependence (AD) and Major Depressive Disorder (MDD) are among the most frequent psychiatric disorders in the general population, and the co-occurrence of those disorders represents a significant public health problem. Levels of alcohol use have been shown to be associated with levels of depressive symptoms among comorbid populations. Previous medication trials with SSRI antidepressants in this comorbid population have produced disappointing results. Mirtazapine is a non-SSRI medication with a unique structure and mechanism of action. Recent study results suggest that mirtazapine may be more effective and faster acting than other antidepressants. Our own recent open label pilot study suggested robust within-group efficacy for mirtazapine for decreasing both the drinking and the depressive symptoms of AD/MDD subjects. However, no placebo control group was employed in that study, so between-group efficacy versus placebo could not be assessed. The current grant submission proposes to conduct a first double-blind, placebo-controlled pilot study to provide a preliminary assessment of the efficacy of mirtazapine versus placebo for decreasing the alcohol use and depressive symptoms of persons with comorbid AD/MDD. If the results of this proposed double-blind pilot study are promising, then the effect sizes found in this proposed study will be used to help design an adequately-powered R01 treatment trial to definitively test the efficacy of mirtazapine versus placebo in this comorbid population.