Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Willingness to reduce alcohol consumption predicted by short-form video exposure, media involvement, psychological bias, and cognitive factor.

Introduction: Through previous studies, Chinese college students are known to be prone to alcohol consumption, which can lead to health-risk behaviors such as high blood pressure, heart disease, stroke, liver disease, and digestive problems. However, little is known about how popular social media platforms (e.g., short-form video applications) can positively impact their willingness to reduce alcohol consumption. This study was guided by the theory of optimistic bias; we investigated the direct, mediated, and moderating effects of exposure to anti-alcohol consumption short-form videos and short-form video involvement on Chinese college students' willingness to reduce their alcohol consumption. Methods: The current study has an empirical cross-sectional design and employed an online survey from September 1st, 2022, to November 1st, 2022. The survey specifically targeted Chinese college students, who are the most common users of short-form video applications. The accumulated data underwent rigorous examination, including hierarchical regression, mediation, and moderation analyses, all conducted using the PROCESS macro 4.0 within SPSS version 22. Results: A total of 434 participants, aged 18-24 years, were included in this study. There were mediating effects regarding Chinese college students' exposure to anti-alcohol consumption short-form videos (ß = 0.35, p < 0.01, 95% CI [0.17, 0.63]) and short-form video involvement (ß = 0.44, p < 0.001, 95% CI [0.20, 0.65]) on their willingness to reduce alcohol consumption via reversed optimistic bias. Moreover, perceived prevention of heavy drinking control (ß = 0.05, p < 0.001, 95% CI [0.01, 0.09]) played mediating roles in the relationship between exposure to anti-alcohol consumption short-form videos and willingness to reduce alcohol consumption. Conclusion: This study is one of the earliest studies to examine the intricate effects of exposure to anti-alcohol consumption short-form videos and short-form video involvement on the willingness to reduce alcohol consumption among Chinese college students. In addition, this study confirms that regardless of whether Chinese college students are conscientious, exposure to anti-alcohol consumption short-form videos did not increase their level of reversed optimistic bias. The empirical findings of this study are critical and can provide practical insights for Chinese health departments that encourage Chinese college students to minimize alcohol consumption.

Gender differences in changes in alcohol consumption achieved by free provision of non-alcoholic beverages: a secondary analysis of a randomized controlled trial.

BACKGROUND: We recently demonstrated that a 12-week intervention consisting of the provision of free non-alcoholic beverages reduced alcohol consumption in excessive drinkers for 8 weeks after the intervention. However, gender differences in this effect were not explored. Thus, this secondary analysis investigated gender differences in the influence of non-alcoholic beverage provision on alcohol consumption. METHODS: Individuals who frequently drank excessively (at least 40 g/day in men and 20 g/day in women) and who were not diagnosed with alcoholism were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total). The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks' of data. In this study, we compared the longitudinal changes in alcohol consumption between genders in both groups. RESULTS: The provision of non-alcoholic beverages significantly reduced alcohol consumption in both genders; however, significant differences in alcohol consumption between the control and intervention groups were observed only in men. The average alcohol consumption during the intervention fell below the level associated with a high risk of non-communicable diseases in men (32.7 g/day), but not in women (24.8 g/day). Correlation coefficient analysis showed that replacing alcoholic beverages with the provided non-alcoholic beverages resulted in different drinking patterns according to gender. The percent changes in the consumption of alcoholic and non-alcoholic beverages relative to baseline levels did not differ between genders. CONCLUSIONS: Our results suggest that the provision of non-alcoholic beverages reduced alcohol consumption irrespective of gender. Of note, providing non-alcoholic beverages might be particularly useful for reducing high-risk alcohol consumption in male excessive drinkers. TRIAL REGISTRATION: UMIN UMIN000047949. Registered 4 June 2022.

Effect of provision of non-alcoholic beverages on alcohol consumption: a randomized controlled study.

BACKGROUND: The use of alcohol-flavored beverages not containing alcohol (hereinafter referred to as non-alcoholic beverages) is recommended to reduce alcohol consumption. However, it is unclear if this reduces excessive drinking. OBJECTIVE: To verify whether non-alcoholic beverages impact the alcohol consumption of excessive drinkers. STUDY DESIGN: Single-center, open-label, randomized, parallel-group study. METHODS: Participants aged 20 years or older who were not diagnosed with alcoholism, who drank at least four times a week, and whose alcohol consumption on those days was at least 40 g in males and 20 g in females, were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total), and thereafter, the number of alcoholic and non-alcoholic beverages consumed were recorded for up to 20 weeks. The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks of data. The primary endpoint was the change from baseline in total alcohol consumption during past 4 weeks at week 12. The participants were not blinded to group allocations. RESULTS: Fifty-four participants (43.9%) were allocated to the intervention group and 69 (56.1%) to the control group. None of the participants in the intervention group dropped out, compared to two (1.6%) in the control group. The change in alcohol consumption was - 320.8 g (standard deviation [SD], 283.6) in the intervention group and - 76.9 g (SD, 272.6) in the control group at Week 12, indicating a significant difference (p < 0.001). Even at Week 20 (8 weeks after the completion of the intervention), the change was - 276.9 g (SD, 39.1) in the intervention group, which was significantly greater than - 126.1 g (SD, 41.3) in the control group (p < 0.001). The Spearman rank correlation coefficient between the change in non-alcoholic beverage consumption and alcohol consumption at Week 12 was significantly negative only in the intervention group (ρ = - 0.500, p < 0.001). There were no reports of adverse events during the study. CONCLUSIONS: Providing non-alcoholic beverages significantly reduced alcohol consumption, an effect that persisted for 8 weeks after the intervention. TRIAL REGISTRATION: UMIN UMIN000047949. Registered 4 June 2022.

Combination treatment with varenicline and naltrexone reduces World Health Organization risk drinking levels.

BACKGROUND: The U.S. Food and Drug Administration identifies abstinence and the absence of heavy drinking days as outcomes for pharmacotherapy trials for alcohol use disorder (AUD). However, many individuals with AUD struggle to achieve these outcomes, which may discourage them from seeking treatment. World Health Organization (WHO) risk drinking levels have garnered attention in the alcohol field as potential non-abstinent outcomes for AUD medication trials. Further, testing combination pharmacotherapy for AUD represents an important direction in the field, particularly using medications such as naltrexone and varenicline, which are approved for treating AUD and smoking, respectively. The objective of the current study was to test the utility of the WHO risk drinking levels as a drinking outcome in a randomized clinical trial of combined varenicline and naltrexone for smoking cessation and drinking reduction. These analyses provide additional tests of the efficacy of this combination treatment. METHODS: The current study is a secondary analysis of a phase 2, randomized, double-blind clinical trial, wherein participants (N = 165) who were daily smokers and heavy drinkers were randomly assigned to receive either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus placebo for 12 weeks. Medication effects on 1- and 2-level reductions in WHO risk drinking levels were assessed at 4, 8, and 12 weeks into the active medication period. RESULTS: In logistic growth curve models individuals receiving the combined treatment had greater reductions in WHO risk drinking levels than individuals taking varenicline alone when assessed at 4 weeks into the active medication period. Among individuals who were WHO high and very high risk drinkers at baseline, the largest effect sizes favoring combination treatment were at Week 4 for the WHO 2-level reduction outcome (Cohen's h = 0.202) and Week 12 for the WHO 1-level reduction outcome (Cohen's h = 0.244), although these effects did not reach statistical significance. CONCLUSIONS: These findings provide evidence that combined varenicline plus naltrexone treatment is effective at reducing WHO risk drinking levels, particularly among individuals who smoke cigarettes daily and drink heavily. These results add to a growing body of literature validating reductions in WHO risk drinking levels as outcomes of alcohol medication trials.

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

BACKGROUND: The World Health Organization (WHO) categorizes alcohol consumption according to grams consumed into low-, medium-, high-, and very-high-risk drinking levels (RDLs). Although abstinence has been considered the ideal outcome of alcohol treatment, reductions in WHO RDLs have been proposed as primary outcomes for alcohol use disorder (AUD) trials. OBJECTIVE: The current study examines the stability of WHO RDL reductions and the association between RDL reductions and long-term functioning for up to 3 years following treatment. DESIGN AND PARTICIPANTS: Secondary data analysis of patients with AUD enrolled in the COMBINE Study and Project MATCH, two multi-site, randomized AUD clinical trials, who were followed for up to 3 years post-treatment (COMBINE: n = 694; MATCH: n = 806). MEASURES: Alcohol use was measured via calendar-based methods. We estimated all models in the total sample and among participants who did not achieve abstinence during treatment. KEY RESULTS: One-level RDL reductions were achieved by 84% of patients at the end of treatment, with 84.9% of those individuals maintaining that reduction at a 3-year follow-up. Two-level RDL reductions were achieved by 68% of patients at the end of treatment, with 77.7% of those individuals maintaining that reduction at a 3-year follow-up. One- and two-level RDL reductions at the end of treatment were associated with significantly better mental health, quality of life (including physical quality of life), and fewer drinking consequences 3 years after treatment (p < 0.05), as compared to no change or increased drinking. CONCLUSION: AUD patients can maintain WHO RDL reductions for up to 3 years after treatment. Patients who had WHO RDL reductions functioned significantly better than those who did not reduce their drinking. These findings are consistent with prior reports suggesting that drinking reductions, short of abstinence, yield meaningful improvements in patient health, well-being, and functioning.

World Health Organization risk drinking level reductions are associated with improved functioning and are sustained among patients with mild, moderate and severe alcohol dependence in clinical trials in the United States and United Kingdom.

AIMS: To examine whether World Health Organization (WHO) risk-level reductions in drinking were achievable, associated with improved functioning and maintained over time among patients at varying initial alcohol dependence severity levels. Design and setting Secondary data analysis of multi-site randomized clinical trials: the US Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study and the UK Alcohol Treatment Trial (UKATT). PARTICIPANTS: Individuals with alcohol dependence enrolled in COMBINE (n = 1383; 68.8% male) and seeking treatment for alcohol problems in UKATT (n = 742; 74.1% male). Interventions Naltrexone, acamprosate or placebo, and combined behavioral intervention or medication management in COMBINE. Social behavior network therapy or motivational enhancement therapy in UKATT. MEASUREMENTS: WHO risk-level reductions were assessed via the calendar method. Alcohol dependence was measured by the Alcohol Dependence Scale, the Leeds Dependence Questionnaire and the Diagnostic and Statistical Manual of Mental Disorders. Measures of functioning included alcohol-related consequences (Drinker Inventory of Consequences and Alcohol Problems Questionnaire), mental health (Short Form Health Survey) and liver enzyme tests. FINDINGS: One- and two-level reductions in WHO risk levels in the last month of treatment were maintained at the 1-year follow-up [adjusted odds ratio (OR), 95% confidence interval (CI) = one-level reduction in COMBINE: 3.51 (2.73, 4.29) and UKATT: 2.65 (2.32, 2.98)] and associated with fewer alcohol-related consequences [e.g. B, 95% CI = one-level reduction COMBINE: -26.22 (-30.62, -21.82)], better mental health [e.g. B, 95% CI = one-level reduction UKATT: 9.53 (7.36, 11.73)] and improvements in γ-glutamyltransferase [e.g. B, 95% CI = one-level reduction UKATT: -89.77 (-122.50, -57.04)] at the end of treatment, even among patients with severe alcohol dependence. Results were similar when abstainers were excluded. Conclusions Reductions in World Health Organization risk levels for alcohol consumption appear to be achievable, associated with better functioning and maintained over time in both the United States and the United Kingdom.

Maintenance of World Health Organization Risk Drinking Level Reductions and Posttreatment Functioning Following a Large Alcohol Use Disorder Clinical Trial.

BACKGROUND: Reductions in the World Health Organization (WHO) risk drinking levels have been proposed as an alternative primary outcome for alcohol clinical trials. Yet, little is known about whether reductions in WHO risk drinking levels can be maintained over time. The current study examined whether reductions in WHO risk drinking levels were maintained for up to 1 year following treatment, and whether reductions over time were associated with improvements in functioning. METHODS: Secondary data analysis of individuals with alcohol dependence (n = 1,226) enrolled in the COMBINE study, a multisite, randomized, placebo-controlled clinical trial. Logistic regression was used to examine the maintenance of end-of-treatment WHO risk level reductions and WHO risk level reductions at the 1-year follow-up. Repeated-measures mixed models were used to examine the association between WHO risk level reductions and functional outcomes over time. RESULTS: Achieving at least a 1- or 2-level reduction in risk by the end of treatment was significantly associated with WHO risk level reductions at the 1-year follow-up assessment (p < 0.001). Among individuals who achieved at least a 1-level reduction by the end of treatment, 85.5% reported at least a 1-level reduction at the 1-year follow-up. Among individuals who achieved at least a 2-level reduction by the end of treatment, 77.8% reported at least a 2-level reduction at the 1-year follow-up. WHO risk level reductions were associated with significantly lower alcohol consumption, better physical health (p < 0.01), and fewer alcohol-related consequences (p < 0.001) up to 1 year following treatment. CONCLUSIONS: One- and 2-level reductions in WHO risk levels during alcohol treatment were maintained after treatment and associated with better functioning over time. These findings support the use of the WHO risk level reductions as an outcome measure that reflects clinically significant improvement in how individuals seeking treatment for alcohol use disorder feel and function.

Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder.

BACKGROUND: Abstinence and no heavy drinking days are currently the only Food and Drug Administration-approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One- and two-level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence. METHODS: Secondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo-controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self-reported quality of life following treatment for alcohol dependence. RESULTS: One- and two-level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001). CONCLUSIONS: One- and two-level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person "feels and functions" following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life.

Clinical Validation of Reduced Alcohol Consumption After Treatment for Alcohol Dependence Using the World Health Organization Risk Drinking Levels.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent public health problem associated with considerable individual and societal costs. Abstinence from alcohol is the most widely accepted target of treatment for AUD, but it severely limits treatment options and could deter individuals who prefer to reduce their drinking from seeking treatment. Clinical validation of reduced alcohol consumption as the primary outcome of alcohol clinical trials is critical for expanding treatment options. One potentially useful measure of alcohol treatment outcome is a reduction in the World Health Organization (WHO, International Guide for Monitoring Alcohol Consumption and Related Harm. Geneva, Switzerland, 2000) risk levels of alcohol use (very high risk, high risk, moderate risk, and low risk). For example, a 2-shift reduction in WHO risk levels (e.g., high risk to low risk) has been used by the European Medicines Agency (2010, Guideline on the Development of Medicinal Products for the Treatment of Alcohol Dependence. UK) to evaluate nalmefene as a treatment for alcohol dependence (AD; Mann et al. 2013, Biol Psychiatry 73, 706-13). METHODS: The current study was a secondary data analysis of the COMBINE study (n = 1,383; Anton et al., ) to examine the association between reductions in WHO risk levels and reductions in alcohol-related consequences and mental health symptoms during and following treatment in patients with AD. RESULTS: Any reduction in WHO risk drinking level during treatment was associated with significantly fewer alcohol-related consequences and improved mental health at the end of treatment and for up to 1 year posttreatment. A greater reduction in WHO risk drinking level predicted a greater reduction in consequences and greater improvements in mental health. CONCLUSIONS: Changes in WHO risk levels appear to be a valid end point for alcohol clinical trials. Based on the current findings, reductions in WHO risk drinking levels during treatment reflect meaningful reductions in alcohol-related consequences and improved functioning.