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

ABSTRACT: 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.

SUBMITTER: Witkiewitz K

PROVIDER: S-EPMC6286196 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Witkiewitz Katie K Kranzler Henry R HR Hallgren Kevin A KA O'Malley Stephanie S SS Falk Daniel E DE Litten Raye Z RZ Hasin Deborah S DS Mann Karl F KF Anton Raymond F RF

Alcoholism, clinical and experimental research 20181105 12

<h4>Background</h4>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 reduce ...[more]

PMID: 30395350

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Project description:BackgroundReductions 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.MethodsSecondary 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.ResultsAchieving 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.ConclusionsOne- 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.

Project description:BackgroundThe 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.ObjectiveThe 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 participantsSecondary 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).MeasuresAlcohol 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 resultsOne-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.ConclusionAUD 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.

Project description:BackgroundGhrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD).MethodsWe used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3 µg/kg) followed by continuous infusion (16.9 ng/kg/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self-administration (IV-ASA) session and the second experiment included an IV alcohol clamp (IV-AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session.ResultsIn both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV-ASA q-value = 0.0003 and IV-AC q < 0.0001), corticosterone (IV-ASA q = 0.0202 and IV-AC q < 0.0001), and glycochenodeoxycholic acid (IV-ASA q = 0.0375 and IV-AC q = 0.0013). In the IV-ASA experiment, ghrelin infusion increased levels of cortisone (q = 0.0352) and fatty acids 18:1 (q = 0.0406) and 18:3 (q = 0.0320). Moreover, in the IV-AC experiment, ghrelin infusion significantly increased levels of glycocholic acid (q < 0.0001) and phenylalanine (q = 0.0458).ConclusionIV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine-conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.

Project description:BackgroundAlcohol-induced blackouts, a form of anterograde amnesia that restricts the encoding of short-term memories into long-term ones, are among the most severe alcohol-related consequences. College students are at high risk of experiencing alcohol-induced blackouts, and there is a need to determine whether alcohol interventions can effectively reduce blackouts in this population. The current study uses data from 3 randomized clinical trials to examine the effect of various intervention approaches on alcohol-induced blackouts.MethodsFour interventions were compared over 3 studies: (i) a computerized feedback intervention (electronic Check-Up To Go [e-Chug]; Study 1); (ii) a single-session brief motivational intervention (BMI; Study 1); (iii) a BMI plus behavioral economic session focused on increasing substance-free activities (BMI + Substance-Free Activity Session [SFAS]; Studies 2 and 3); and (iv) a BMI plus supplemental Relaxation Training session (BMI + Relaxation Training; Studies 2 and 3). Studies 1 and 3 also included an assessment-only control condition. For each study, participants reported whether they had experienced an alcohol-induced blackout at each time point; binary logistic regressions examined differential likelihood of experiencing an alcohol-induced blackout over time.ResultsNeither the single-session BMI nor e-Chug reduced alcohol-induced blackouts over assessment only; however, participants in the BMI + SFAS or BMI + Relaxation Training condition were significantly less likely to experience an alcohol-induced blackout compared to assessment only at 1-month (Wald = 4.77, odds ratio [OR] = 0.53, p = 0.03) and 6-month follow-ups (Wald = 5.72, OR = 0.52, p = 0.02). Study 2 also revealed a larger effect for the BMI + SFAS over the BMI + Relaxation Training condition at 6 months (Wald = 4.11 OR = 0.22, p = 0.043), although this was not replicated in Study 3. The effects for the 2-session BMIs lasted 6 months, at which point maturation effects diminished differences between assessment-only and intervention conditions.ConclusionsTwo sessions of BMI are a substantial enough dose to result in reductions in alcohol-induced blackouts among college student heavy drinkers.

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

Publications

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

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