Acetyl-L-carnitine supplementation for co-occurring depression and alcohol use disorder in adolescents: A randomized placebo-controlled pilot study

项目摘要/摘要 青春期是饮酒和抑郁风险增加的时期。抑郁症和抑郁症的并存 酒精使用障碍(AUD)是年轻人中最普遍和最致残的精神疾病组合之一。这个 高患病率使这种共病成为治疗的标准，青少年也在与这种共病作斗争。 表现出不良的治疗结果。因此，这些人口有相当大的需求，目前还没有得到满足 可用的治疗方法。改善青少年共病酒精治疗的一种潜在方法 抑郁症是通过药物治疗来加强可用的最好的心理社会干预措施 同时治疗这两种情况。目前有四种FDA批准的药物用于治疗 成人中的AUD。然而，在青少年AUD和对照临床试验中没有药物治疗的迹象。 青少年明显缺席了文学课。改善年轻人的治疗选择将需要关闭这个 药物开发研究中的重要差距。这一为期两年的筹备项目(R21)将支持 收集综合疗法的试点数据，该疗法结合了一种有希望的新药，显示出可减少 成人的抑郁症状，即快感缺乏和酒精渴求，具有社会心理的黄金标准 干预对青少年AUD的治疗。具体来说，我们将使用严格的协议嵌入 人体实验室和生态学瞬时方法在随机安慰剂对照试验背景下的检查 如果我们的候选药物，乙酰肉碱-L-卡尼汀，增强了心理社会治疗的效果 在患有抑郁症的青少年中。我们的具体目标是：a)评估可行性、可接受性和 乙酰-L-卡尼汀对伴发抑郁症的青少年的耐受性；b)检测乙酰-L-卡尼汀 肉碱在人体实验室和现实环境中减少酒精渴望，并钝化强化 日常饮酒时饮酒的影响；c)测试乙酰肉碱是否能降低抑郁情绪， 抑郁症状和快感减退；以及d)测试乙酰肉碱-L-卡尼汀是否减少酒精的使用 人口。我们的目标是解决国家优先事项，收集用于治疗的药物的安全性和有效性数据 在年轻的时候。这项探索性研究的发现将有助于通过以下方式为AUD提供个性化药物 建立针对共发抑郁症和AUD的地方性内表型的证据。这个 建议的R21也将为未来乙酰基-L-肉碱的大规模临床试验提供关键的先导数据 人口。这一奖项与NIH满足全国临床研究需求的目标一致。

PROJECT SUMMARY/ABSTRACT Adolescence is a time of increased risk for alcohol use and depression. The co-occurrence of depression and alcohol use disorder (AUD) is one of the most prevalent and disabling psychiatric combinations in youth. The high prevalence makes this comorbidity a treatment norm and adolescents who struggle with this comorbidity exhibit poor treatment outcomes. As such, this population has considerable needs that are currently unmet by available treatments. One potential way to improve alcohol treatment for adolescents who have co-occurring depression is to augment the best available psychosocial interventions with pharmacotherapy designed to simultaneously treat both conditions. Currently there are four FDA approved medications for the treatment of AUD in adults. However, no medication is indicated for AUD in adolescents and controlled clinical trials with teenagers are noticeably absent for the literature. Improving treatment options for youth will require closing this important gap in medication development research. This two-year preparatory project (R21) will support the collection of pilot data for an integrative therapy that combines a promising novel medication, shown to reduce depressive symptoms, namely anhedonia, and alcohol craving in adults, with a gold standard psychosocial intervention for treating AUD among adolescents. Specifically, we will use rigorous protocol that embeds human lab and ecological momentary methods in the context of randomized placebo-controlled trial to examine if our candidate pharmacotherapy, acetyl-L-carnitine, enhances the effects of psychosocial treatment for AUD in adolescents with comorbid depression. Our specific aims are to: a) evaluate the feasibility, acceptability, and tolerability of acetyl-L-carnitine in adolescents with comorbid depression and AUD; b) test whether acetyl-L- carnitine decreases alcohol craving in the human laboratory and real-world setting and blunts the reinforcing effects of alcohol while drinking in daily life; c) test whether acetyl-L-carnitine reduces depressed mood, depression symptoms, and anhedonia; and d) test whether acetyl-L-carnitine decreases alcohol use in this population. Our aims address national priorities to gather safety and efficacy data on medications for treating AUD in youth. Findings from this exploratory study will contribute to personalized medicine for AUD by establishing evidence for targeting endophenotypes endemic to co-occurring depression and AUD. The proposed R21 will also provide critical pilot data for a future large-scale clinical trial of acetyl-L-carnitine in this population. This award is consistent with NIH's goal to address the nation's clinical research needs.