Alcohol Use Disorder Treatment: The Association of Pretreatment Use and the Role of Drinking Goal

BACKGROUND: In a recent study conducted in a family medicine setting, the medication acamprosate was found not to be efficacious in the treatment of alcohol dependence, but a drinking goal of abstinence was found to have positive effects on alcohol use outcomes. The purpose of this secondary analysis was to further understand which patients with an alcohol use disorder may be most successfully treated in a primary care setting. METHODS: The study was exploratory and used a trajectory-based approach based on data from the acamprosate treatment trial of 100 participants (recruited mostly by advertisement) who were randomly assigned to receive either acamprosate or a matching placebo. Post hoc trajectories of alcohol use before treatment were identified to examine whether trajectory classes and their interactions with treatment arm (acamprosate or placebo), pretreatment drinking goal (abstinence or a reduction), and time predicted alcohol use outcomes. RESULTS: Three distinct trajectory classes were identified: frequent drinkers, nearly daily drinkers, and consistent daily drinkers. Consistent daily drinkers with a goal of abstinence significantly improved over time on the primary outcome measure of percent days abstinent when compared with frequent and nearly daily drinkers. In addition, all participants with a goal of abstinence, regardless of trajectory class, significantly reduced their percentage of heavy drinking days over time. CONCLUSIONS: Patients with an alcohol use disorder who have a drinking goal of abstinence, in particular consistent daily drinkers, may maximally benefit from alcohol use disorder treatment, including the use of medication, in a primary care setting

Association of the Sweet-Liking Phenotype and Craving for Alcohol With the Response to Naltrexone Treatment in Alcohol Dependence: A Randomized Clinical Trial

Identification of moderators of the response to naltrexone hydrochloride treatment for alcohol dependence could improve clinical care for patients with alcohol use disorders. To investigate the preliminary finding that the sweet-liking (SL) phenotype interacts with a high level of craving for alcohol and is associated with an improved response to naltrexone in alcohol dependence. This 12-week double-blind, randomized, placebo-controlled clinical trial was conducted from February 1, 2010, to April 30, 2012, in an academic outpatient medical center. Eighty actively drinking patients were randomized by the SL (n = 22) or the sweet-disliking (SDL) (n = 58) phenotype and by pretreatment high (n = 40) or low (n = 40) craving for alcohol, with high craving defined as greater than the median. Patients and staff were blinded to categorization. Patients were excluded for unstable medical or psychiatric illness, including dependence on drugs other than nicotine. Four patients (2 in the placebo arm and 2 in the naltrexone arm) stopped medication therapy because of adverse effects. Data were analyzed from January 15, 2013, to May 15, 2016, based on intention to treat. Oral naltrexone hydrochloride, 50 mg/d, or daily placebo with weekly to biweekly brief counseling. The a priori hypothesis tested SL/SDL phenotype, pretreatment craving, and their interaction as moderators of frequency of abstinent and heavy drinking days during treatment, assessed with the timeline follow-back method. Eighty patients were randomized (57 men [71%]; 23 women [29%]; mean [SD] age, 47.0 [8.6] years). A nonsignificant effect of naltrexone on heavy drinking was noted (4.8 fewer heavy drinking days; Cohen d = 0.45; 95% CI, -0.01 to 0.90; F1,67 = 3.52; P = .07). The SL phenotype moderated the effect of naltrexone on heavy drinking (6.1 fewer heavy drinking days; Cohen d = 0.58; 95% CI, 0.12-1.03; F1,67 = 5.65; P = .02) and abstinence (10.0 more abstinent days; Cohen d = 0.57; 95% CI, 0.11-1.02; F1,67 = 5.36; P = .02), and high craving moderated heavy drinking (7.1 fewer heavy drinking days; Cohen d = 0.66; 95% CI, 0.20-1.11; F1,67 = 7.37; P = .008). The combination of the SL phenotype and high craving was associated with a strong response to naltrexone, with 17.1 fewer heavy drinking days (Cohen d = 1.07; 95% CI, 0.58-1.54; F1,67 = 19.33; P < .001) and 28.8 more abstinent days (Cohen d = 0.72; 95% CI, 0.25-1.17; F1,67 = 8.73; P = .004) compared with placebo. The SL phenotype and a high craving for alcohol independently and particularly in combination are associated with a positive response to naltrexone. The SL/SDL phenotype and a high craving for alcohol merit further investigation as factors to identify patients with alcohol dependence who are responsive to naltrexone. clinicaltrials.gov Identifier: NCT01296646

Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (FHP) were compared to 15 young men without a family history of alcoholism (FHN). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148 ± 36 mg/kg/hr, compared to FHN subjects, 124 ± 18 mg/kg/hr, p=.01. However, FHN subjects increased their rate of metabolism by 10 ± 27 percent compared to a decrease of -15 ± 24 percent in FHP subjects, p =.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, p=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence

Unipolar depression does not moderate responses to the Sweet Taste Test

The Sweet Taste Test (STT) measures hedonic responses to sweet tastes and has been linked to both alcoholism and to a family history of alcoholism. However, STT response profiles in unipolar major depressive disorder (MDD), a disorder characterized by anhedonia, have been minimally investigated

Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

Recent clinical trials and case-reports indicate that baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol dependent individuals in two placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States

Intact hedonic responses to sweet tastes in autism spectrum disorder

The Sweet Taste Test (STT) is a standardized measure designed to index the ability to detect differences in sweet tastes (sweet taste sensitivity) and hedonic responses to sweet tastes (sweet taste liking). Profiles of response on the STT suggest enhanced hedonic responses to sweet tastes in psychiatric disorders characterized by dysfunctional reward processing systems, including binge-eating disorders and substance use disorders, and a putative mechanism governing STT responses is the brain opioid system. The present study examined STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy control adults. There were no differences in sweet taste sensitivity or hedonic response to sweet tastes between the ASD and control groups. Within the ASD sample, ASD symptom severity was associated with sweet taste sensitivity, but not hedonic response to sweet taste. Results may ultimately shed light on brain opioid system functioning in ASD

Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects

The neuropeptide, oxytocin, has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that oxytocin administered by the intranasal route penetrates into and exerts effects within the brain

Woodland, cropland and hedgerows promote pollinator abundance in intensive grassland landscapes, with saturating benefits of flower cover

1. Pollinating insects provide economic value by improving crop yield. They are also functionally and culturally important across ecosystems outside of cropland. To understand landscape-level drivers of pollinator declines, and guide policy and intervention to reverse declines, studies must cover (a) multiple insect and plant taxa and (b) a range of agricultural and semi-natural land uses. Furthermore, in an era of woodland restoration initiatives and rewilding ideologies, the contribution of woodland and woody linear features (WLFs; e.g. hedgerows) to pollinator abundance demands further investigation. 2. We demonstrate fine-scale analysis of high-quality, co-located measurements from a national environmental survey. We relate pollinator transect counts to ground-truth habitat and WLF maps across 300 1 km squares in Wales, UK. We look at effects of habitat type, flower cover, WLF density and habitat diversity on summer abundance (July and August) of eight insect groups, representing three insect orders (Lepidoptera, Hymenoptera and Diptera). 3. Compared with improved grassland (the dominant habitat in Wales), pollinator abundance is consistently higher in cropland and woodland—especially broadleaved woodland. For mining bees and two hoverfly groups, abundance is predicted to be at least 1.5× higher in woodland ecosystems than elsewhere. Furthermore, we estimate contributions of WLFs to abundance in agriculturally improved habitats to be up to 14% for honeybees and up to 21% for hoverflies. 4. The abundance of all insect groups increases with flower cover, which is a key mechanism through which woodland, cropland and grassland support pollinators. Importantly, we observe diminishing returns of increasing flower cover for abundance of non-Apis pollinator groups, expecting roughly twice the increase in abundance per % flower cover from 0% to 5%, as compared with 10% to 15%. However, the shape of the relationship was inverted for honeybees, which showed steeper increases in abundance at higher flower cover. 4. Synthesis and applications: We provide a holistic view of the drivers of pollinator abundance in Wales, in which flower cover, woodland, hedgerows and cropland are critical. We propose a key role for woodland creation, hedge-laying and farmland heterogeneity within future land management incentive schemes. Finally, we suggest targeting of interventions to maximise benefits for non-Apis pollinators. Specifically, increasing floral provision in areas where existing flower cover is low—for example, in flower-poor improved grasslands—could effectively increase pollinator abundance and diversity while prioritising wild over managed species