Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials A Secondary Analysis of 3 Randomized Clinical Trials
Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials A Secondary Analysis of 3 Randomized Clinical Trials
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DOI：
10.1001/jamapsychiatry.2018.3079
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发表时间：
2019-04-01
期刊：
影响因子：
25.8
通讯作者：
Ramey, Tanya
中科院分区：
文献类型：
--
作者：
Falk, Daniel E.;O'Malley, Stephanie S.;Ramey, Tanya
重要性：美国食品和药物管理局承认完全戒酒和无大量饮酒日是酒精使用障碍（AUD）关键药物治疗试验的结果。许多患者很难达到这些结果，这可能会阻碍寻求治疗，并减缓了影响酒精使用的药物的开发。目的比较完全戒酒和不重度饮酒的两种减少饮酒的结果。设计、环境和参与者数据来自3个多地点、随机、安慰剂对照的临床试验，这些试验是针对dsm - iv分类的酒精依赖成人患者治疗酒精依赖的药物（纳曲酮、伐尼克兰和托吡酯）。在每项试验中，积极和安慰剂条件下符合戒断、无重度饮酒天数、who 1级降低和who 2级降低定义的参与者的百分比按月计算，并具有相应的效应量（Cohen h）。结果在这3项试验中（N = 1169，平均年龄45岁，824名男性，70.5%），在治疗的最后4周被分类为有反应的参与者比例最低的是戒酒（纳曲酮，34.7%[100 / 288]；伐尼克兰，7.3%[96 / 96]；托吡酯，11.7%[21 / 179]），其次是不重度饮酒（纳曲酮，51.0%[147 / 288]；伐尼克兰，24.0%[23 / 96]；托吡酯，20.7%[37 / 179]），WHO 2级降低(纳曲酮，75.0%[216 / 288]；伐尼克兰，55.2%[53 / 96]；托吡酯，44.7%[179 / 80])和WHO 1级降低（纳曲酮，83.3%[288 / 240]；伐尼克兰，69.8[96 / 67]；托吡酯，54.7%[179 / 98]）结果。who2水平降低结果（纳曲酮，Cohen h = 0.214 [95% CI, 0.053 -0.375]；伐尼克兰，0.273 [95% CI, -0.006 - 0.553]；托吡酯，0.230 [95% CI, 0.024-0.435]）和who1水平降低（纳曲酮，Cohen h = 0.116 [95% CI, -0.046 - 0.277]；伐尼克兰，0.338 [95% CI, 0.058-0.617]；托吡酯，0.014 [95% CI, -0.192 - 0.219]）的标准化治疗效果与戒断获得的结果(纳曲酮，Cohen h = 0.142 [95% CI, -0.020-0.303]；伐尼克兰，0.146 [95% CI, -0.133至0.426]；托吡酯，0.369 [95% CI, 0.163-0.574])和无重度饮酒天数（纳曲酮，Cohen h = 0.140 [95% CI, -0.021 - 0.302]；伐尼克兰，0.232 [95% CI, -0.048 - 0.511]；托吡酯，0.207 [95% CI, 0.002-0.413]）。结论和相关性在AUD药物治疗试验中，who饮酒风险水平的降低似乎是治疗结果的值得指标。这些结果可能与许多患者减少饮酒的目标一致，并且比戒酒或不大量饮酒的日子获得更多患者经历的临床有意义的改善。
IMPORTANCE The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use.OBJECTIVE To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes.DESIGN, SETTING, AND PARTICIPANTS Datawere obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence.MAIN OUTCOMES AND MEASURES Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h).RESULTS Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4weeks of treatmentwas lowest for abstinence (naltrexone, 34.7%[100 of 288]; varenicline, 7.3%[7 of 96]; topiramate, 11.7%[21 of 179]) followed by no heavy drinking days (naltrexone, 51.0%[147 of 288]; varenicline, 24.0%[23 of 96]; topiramate, 20.7%[37 of 179]), WHO 2-level reduction (naltrexone, 75.0%[216 of 288]; varenicline, 55.2%[53 of 96]; topiramate, 44.7%[80 of 179]), and WHO 1-level reduction (naltrexone, 83.3%[240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7%[98 of 179]) outcomes. Standardized treatment effects observed for the WHO2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020-0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]).CONCLUSIONS AND RELEVANCE WHOdrinking risk level reductions appear to beworthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomesmay align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days.