Identifying treatment responders to the combination of varenicline and naltrexone.

IF 1.9 4区 医学 Q2 SUBSTANCE ABUSE
Suzanna Donato, Lara A Ray
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引用次数: 0

Abstract

Background and objectives: The heterogeneity of alcohol and tobacco co-use suggests that only a subset of individuals will respond to a given pharmacotherapy. Toward identifying treatment responders, statistical learning was applied to a clinical trial combining naltrexone and varenicline for smoking cessation and drinking reduction.

Method: Individuals (N = 165) who smoke cigarettes daily and drink alcohol heavily completed a Phase 2, double blind, randomized clinical trial comparing the efficacy of combination varenicline plus naltrexone versus varenicline plus placebo. Smoking cessation was defined by bio-verified nicotine abstinence. Drinking reduction was defined as a 2-level reduction in the World Health Organization (WHO) risk drinking level. Three statistical learning methods (ridge regression, LASSO regression, and random forest) were tested psychosocial and biological predictors of clinical response.

Results: For drinking reduction, the LASSO regression had the highest overall accuracy (86%) and AUC (0.88). Important predictors included baseline alcohol consumption, baseline smoking urge, age of first cigarette use, and years of education. For nicotine abstinence, LASSO regression had the highest overall accuracy AUC (0.69). Important predictors included medication condition, expired alveolar CO level, baseline alcohol consumption, depression symptoms, and years of education.

Conclusions: Baseline consumption patterns are a strong predictor of clinical outcome for both smoking cessation and drinking reduction. Results also underscore the important cross-relationship between drinking and smoking. Statistical learning models converged with previous hypothesis-driven studies and were well-suited for clinical trial datasets.

Scientific significance: These findings highlight candidate variables that, with further validation, may support the development of personalized treatment strategies.

鉴别伐尼克兰和纳曲酮联合治疗的应答者。
背景和目的:酒精和烟草共同使用的异质性表明,只有一小部分个体对给定的药物治疗有反应。为了确定治疗反应,统计学习应用于纳曲酮和伐尼克兰联合戒烟和减少饮酒的临床试验。方法:每天吸烟和大量饮酒的个体(N = 165)完成了一项2期、双盲、随机临床试验,比较了伐尼克兰联合纳曲酮与伐尼克兰联合安慰剂的疗效。戒烟被定义为生物验证的尼古丁戒断。减少饮酒被定义为世界卫生组织(世卫组织)危险饮酒水平降低2级。三种统计学习方法(脊回归、LASSO回归和随机森林)测试了临床反应的社会心理和生物学预测因子。结果:对于减少饮酒,LASSO回归具有最高的总体准确度(86%)和AUC(0.88)。重要的预测因素包括基线饮酒量、基线吸烟冲动、首次吸烟年龄和受教育年限。对于尼古丁戒断,LASSO回归具有最高的总体准确度AUC(0.69)。重要的预测因素包括药物状况、肺泡过期CO水平、基线酒精摄入量、抑郁症状和受教育年限。结论:基线消费模式是戒烟和减少饮酒的临床结果的有力预测因子。研究结果还强调了饮酒和吸烟之间重要的相互关系。统计学习模型与以前的假设驱动研究融合,非常适合临床试验数据集。科学意义:这些发现突出了候选变量,经过进一步验证,可能支持个性化治疗策略的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.00
自引率
0.00%
发文量
118
期刊介绍: The American Journal on Addictions is the official journal of the American Academy of Addiction Psychiatry. The Academy encourages research on the etiology, prevention, identification, and treatment of substance abuse; thus, the journal provides a forum for the dissemination of information in the extensive field of addiction. Each issue of this publication covers a wide variety of topics ranging from codependence to genetics, epidemiology to dual diagnostics, etiology to neuroscience, and much more. Features of the journal, all written by experts in the field, include special overview articles, clinical or basic research papers, clinical updates, and book reviews within the area of addictions.
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