Program on Forced Migration and Health, Columbia University Mailman School of Public Health, New York, New York, USA.
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Cochrane Database Syst Rev. 2023 May 9;5(5):CD013350. doi: 10.1002/14651858.CD013350.pub2.
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
We used standard methodological procedures expected by Cochrane.
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS: In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
有害饮酒是指因饮酒而导致不良的身体、心理、社会或社会后果，并成为全球疾病、残疾和过早死亡的主要风险因素之一的不健康饮酒。在中低收入国家（LMICs），有害饮酒的负担正在增加，在这些环境中，减少有害饮酒的有针对性的预防和治疗干预措施仍有很大的未满足需求。关于哪些干预措施对解决 LMICs 中有害和其他不健康饮酒模式有效和可行的证据有限，这导致了服务方面的差距。
评估心理社会和药物治疗以及有针对性的预防干预措施与对照条件（等待名单、安慰剂、无治疗、标准护理或活性对照条件）相比，在减少 LMICs 中有害饮酒方面的疗效和安全性。
我们在 Cochrane 药物和酒精组（CDAG）专业登记册、Cochrane 图书馆中的 Cochrane 对照试验登记册（CENTRAL）、PubMed、Embase、PsycINFO、CINAHL 和拉丁美洲和加勒比健康科学文献（LILACS）中搜索了随机对照试验（RCTs），并于 2021 年 12 月 12 日进行了检索。我们在 clinicaltrials.gov、世界卫生组织国际临床试验注册平台、Web of Science 和 Opengrey 数据库中搜索了未发表或正在进行的研究。我们还查阅了纳入研究的参考文献列表和相关综述文章，以获取合格的研究。
我们纳入了所有将有针对性的预防或治疗干预（药物或心理社会）与 LMICs 中有害饮酒者的对照条件进行比较的 RCT。
我们使用了 Cochrane 预期的标准方法学程序。
我们纳入了 66 项 RCT，涉及 17626 名参与者。其中 62 项试验纳入了荟萃分析。63 项研究在中等收入国家（MICs）进行，其余 3 项研究在低收入国家（LICs）进行。25 项试验专门招募了有酒精使用障碍的参与者。其余 51 项试验招募了有有害饮酒行为的参与者，其中一些参与者既有酒精使用障碍，也有报告了不符合障碍标准的危险饮酒模式的人。52 项 RCT 评估了心理社会干预的疗效；其中 27 项是基于动机访谈的简短干预措施，与简短建议、信息或评估进行了比较。由于纳入研究的高度异质性，我们不确定有害饮酒的减少是否归因于简短干预措施（报告连续结果的研究：Tau²=0.15，Q=139.64，df=16，P<.001，I²=89%，3913 名参与者，17 项试验，低确定性；报告二分类结果的研究：Tau²=0.18，Q=58.26，df=3，P<.001，I²=95%，1349 名参与者，4 项试验，低确定性）。其他类型的心理社会干预措施包括一系列治疗方法，如行为风险降低、认知行为疗法、行为契约管理、理性情绪疗法和复发预防。这些干预措施最常与涉及各种心理教育、咨询和药物治疗组合的常规护理进行比较。由于纳入研究的高度异质性，我们不确定有害饮酒的减少是否归因于心理社会治疗（异质性：Tau²=1.15；Q=444.32，df=11，P<.001；I²=98%，2106 名参与者，12 项试验，低确定性）。八项试验比较了联合药物和心理社会干预与安慰剂、单独心理社会干预或另一种药物治疗。活性药物研究条件包括双硫仑、纳曲酮、昂丹司琼或托吡酯。这些干预措施的心理社会组成部分包括咨询、鼓励参加匿名戒酒会、动机访谈、简短认知行为疗法或其他心理治疗（未指定）（不是特定的）。对比较联合药物和心理社会干预与单独心理社会干预的研究进行分析发现，联合方法可能与更大程度地减少有害饮酒有关（标准化平均差异（标准化平均差异（SMD））=-0.43，95%置信区间（CI）：-0.61 至-0.24；475 名参与者；4 项试验；低确定性）。四项试验比较了药物干预与安慰剂，三项试验比较了药物干预与另一种药物治疗。评估的药物包括：安非他酮、阿米替林、巴氯芬双硫仑、加巴喷丁、米氮平和纳曲酮。这些试验均未评估有害饮酒这一主要临床结局。31 项试验报告了干预措施的保留率。荟萃分析显示，在任何比较中，研究条件之间的保留率没有差异（药物风险比（RR）=1.13，95%置信区间（CI）：0.89 至 1.44，247 名参与者，3 项试验，低确定性；药物联合心理社会干预：RR=1.15，95%置信区间（CI）：0.95 至 1.40，363 名参与者，3 项试验，中度确定性）。由于高度异质性，我们没有计算比较简短（异质性：Tau²=0.00；Q=172.59，df=11，P<.001；I=94%；5380 名参与者；12 项试验，低确定性）或其他心理社会干预（异质性：Tau²=0.01；Q=34.07，df=8，P<.001；I=77%；1664 名参与者；9 项试验，低确定性）的保留率的汇总估计值。两项药物试验和三项联合药物和心理社会试验报告了副作用。这些研究发现，与米氮平相比，阿米替林的副作用更多，与安慰剂相比，纳曲酮和托吡酯的副作用更多，而与安慰剂相比，阿坎酸或昂丹司琼则没有差异。在所有干预类型中，都存在严重的偏倚风险。主要的有效性威胁包括缺乏盲法和差异/高失访率。
在 LMICs 中，有低确定性证据支持联合心理社会和药物干预措施在减少有害饮酒方面优于心理社会干预单独使用。由于结局、比较和干预措施的高度异质性，我们无法确定药物或心理社会干预在减少有害饮酒方面的疗效，这使得无法对这些数据进行荟萃分析。大多数研究都是简短的干预措施，主要针对男性，并且使用的是未经目标人群验证的措施。由于存在偏倚风险和研究之间以及研究中不同结局测量之间的显著异质性，这些结果的可信度降低。需要更多关于药物干预的有效性以及特定类型的心理社会干预的证据，以提高这些结果的确定性。
