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.

Reductions in World Health Organization Risk Drinking Level Are Associated With Reductions in Alcohol Use Disorder Diagnosis and Criteria: Evidence From an Alcohol Pharmacotherapy Trial.

OBJECTIVES: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria. METHODS: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346). Participants received gabapentin enacarbil extended release or placebo for 6 months. The timeline follow-back was used to assess WHO risk drinking level reductions, and the Mini-International Neuropsychiatric Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria at baseline (past year) and end of treatment (past month). RESULTS: Most participants (80.1%) achieved at least a 1-level reduction in the WHO risk drinking levels from baseline to end of treatment, and nearly half of participants (49.8%) achieved at least a 2-level reduction. At least a 1-level reduction or at least a 2-level reduction in WHO risk drinking level predicted lower odds of an active AUD diagnosis (1-level: odds ratio, 0.74 [95% confidence interval (CI), 0.66-0.84]; 2-level: odds ratio, 0.71 [95% CI, 0.64-0.79]) and fewer AUD criteria (1-level: B, -1.66 [95% CI, -2.35 to -0.98]; 2-level: B, -1.76 [95% CI, -2.31 to -1.21]) at end of treatment. CONCLUSIONS: World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment.

Reductions in WHO risk drinking levels correlate with alcohol craving among individuals with alcohol use disorder.

BACKGROUND: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery. Whether reductions in drinking during AUD treatment are associated with reductions in craving has not been well examined. METHODS: We conducted secondary analyses of data from three AUD clinical trials (N's= 1327, 346, and 200). Drinking reductions from baseline to the end of treatment were measured as changes in World Health Organization (WHO) risk drinking levels; alcohol craving was measured using validated self-report measures. Regression analyses tested whether drinking reductions were associated with end-of-treatment craving reductions; moderation analyses tested whether associations between drinking reduction and end-of-treatment craving differed across AUD severity. RESULTS: Reductions of at least 1 or at least 2 WHO risk drinking levels were associated with lower craving (all p's < 0.05). Results were substantively similar after removing abstainers at the end-of-treatment. Associations between drinking reductions and craving were generally not moderated by AUD severity. CONCLUSIONS: Individuals with WHO risk drinking level reductions reported significantly lower craving, as compared to those who did not achieve meaningful reductions in drinking. The results demonstrate the utility of WHO risk drinking levels as AUD clinical trial endpoints and provide evidence that drinking reductions mitigate craving.

Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey.

INTRODUCTION: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. METHODS: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. RESULTS: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. DISCUSSION: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group.

The Role of Unawareness, Volition, and Neural Hyperconnectivity in Alcohol Use Disorder: A Functional Magnetic Resonance Imaging Study.

BACKGROUND: Automated alcohol craving and habitual alcohol consumption characterize the later stages of alcohol use disorder (AUD). This study reanalyzed previously collected functional neuroimaging data in combination with the Craving Automated Scale for Alcohol (CAS-A) questionnaire to investigate the neural correlates and brain networks underlying automated drinking characterized by unawareness and nonvolition. METHODS: We assessed 49 abstinent male patients with AUD and 36 male healthy control participants during a functional magnetic resonance imaging-based alcohol cue-reactivity task. We performed whole-brain analyses examining the associations between CAS-A scores and other clinical instruments and neural activation patterns in the alcohol versus neutral contrast. Furthermore, we performed psychophysiological interaction analyses to assess the functional connectivity between predefined seed regions and other brain areas. RESULTS: In patients with AUD, higher CAS-A scores correlated with greater activation in dorsal striatal, pallidal, and prefrontal regions, including frontal white matter, and with lower activation in visual and motor processing regions. Between-group psychophysiological interaction analyses showed extensive connectivity between the seed regions inferior frontal gyrus and angular gyrus and several frontal, parietal, and temporal brain regions in AUD versus healthy control participants. CONCLUSIONS: The present study applied a new lens to previously acquired alcohol cue-reactivity functional magnetic resonance imaging data by correlating neural activation patterns with clinical CAS-A scores to elucidate potential neural correlates of automated alcohol craving and habitual alcohol consumption. Our results support previous findings showing that alcohol addiction is associated with hyperactivation in habit-processing regions, with hypoactivation in areas mediating motor and attention processing, and with general hyperconnectivity.

The impact of life satisfaction in the treatment of gaming disorder and other internet use disorders: Results from a randomized controlled trial.

Objective: According to ICD-11 gaming disorder is currently defined as a behavioral addiction. While our understanding of crucial aspects of this new condition including other subtypes of internet use disorders is growing, less is known about treatment strategies and their effectiveness. Particularly, dimensions of life satisfaction and their meaning for internet use disorders are poorly investigated. The aim of this study was addressing the role of life satisfaction dimensions in a randomized controlled trial. We examined life satisfaction as an additional treatment outcome and investigated in how far life satisfaction is predictive for symptom reduction and related to personality traits. Methods: A multicenter randomized controlled trial with three measure points (baseline, post-treatment, 6-month follow-up) was conducted based on N = 143 patients aged 17 and above meeting diagnostic criteria for internet use disorders. A cognitive-behavioral disorder specific intervention was applied in n = 72 and compared to a wait list control (n = 71). Endpoints included symptoms of internet use disorders, psychosocial functioning, and life satisfaction. Personality traits were assessed as moderating factors. Results: Life satisfaction (η2 = 0.106) and health satisfaction (η2 = 0.173) significantly increased in the intervention group with large effect sizes. Decreasing symptoms of internet use disorders at follow-up were predicted by life satisfaction at post-treatment (ß = -0.51) with extraversion (B = 1.606) and openness (B = 2.069) moderating this association. Conclusion: Life satisfaction yields additional value as a secondary treatment outcome in internet use disorders and can be therapeutically addressed in order to stabilize treatment effects in the long run. Our study indicates that existing treatment strategies might benefit from explicitly addressing and enhancing psychosocial resources in order to prevent relapses in patients.

Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in AUD. Here we report a double-blind randomized controlled trial comparing active DBS ("DBS-EARLY ON") against sham stimulation ("DBS-LATE ON") over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving, depressiveness and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples.

Carbohydrate Sources Influence the Microbiota and Flavour Profile of a Lupine-Based Moromi Fermentation.

Lupine-based seasoning sauce is produced similarly to soy sauces and therefore generates a comparable microbiota and aroma profile. While the koji state is dominated by Aspergillus oryzae, the microbiome of the moromi differs to soy moromi, especially in yeast composition due to the absence of Zygosaccharomyces rouxii and Debaryomyces hansenii as the dominant yeast. In this study, we monitored the addition of a carbohydrate source on the microbiome and aroma profile of the resulting sauce. Compared to previous studies, the usage of a yeast starter culture resulted in a sparsely diverse microbiota that was dominated by D. hansenii and T. halophilus. This led to a pH below 5 even after four months of incubation and most of the measured aroma compounds were pyrazines and acids. The addition of wheat and buckwheat resulted in a temporary change in the yeast consortium with the appearance of Z. rouxii and additional bacterial genera. The aroma profile differs in the presence of pyrazines and esters. Since no significant differences in the taste and odour of wheat-added and buckwheat-added sauce was sensed, both substrates influence the lupine sauce in a similar way.

The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study.

RATIONALE: Central aspects of alcohol use disorder (AUD) are the irresistible desire for alcohol and impaired control over its intake. According to the triadic neurocognitive model of addiction, this arises from aberrant functioning of different neural and cognitive systems: an impulsive system, a reflective system, and the abnormal dynamics between both systems based on an insular-dependent system. OBJECTIVES: In this study, we examined the effects of a single dose of nalmefene on resting-state functional connectivity (rsFC) patterns within and between these addiction-related neural systems in AUD. METHODS: Non-treatment seeking participants with AUD (N = 17; 19-66 years, 6 female) took part in a randomized, placebo-controlled, double-blind, crossover study and received either a single dose of 18 mg nalmefene or a placebo. Using seed-based correlation analyses on resting-state functional magnetic resonance imaging data, we examined the effects of nalmefene on key nodes related to the (1) impulsive system; (2) reflective system; (3) salience network; and (4) default mode network. RESULTS: Under nalmefene, participants showed reduced rsFC between components of the impulsive system (Nucleus accumbens-putamen/pallidum/insula). Reduced rsFC was found between elements of the reflective system and impulsive system (orbitofrontal cortex-insula/putamen/pallidum), salience network (orbitofrontal cortex-insula/inferior frontal gyrus), and default mode network (lateral prefrontal cortex-precuneus/cuneus). Components of the salience network showed both increased (anterior cingulate cortex) and decreased (insular cortex) rsFC to elements of the reflective system. CONCLUSION: A single dose of nalmefene impacts rsFC and alters the interaction between key nodes of addiction-related neural systems in non-treatment seeking participants with AUD. Nalmefene may normalize rsFC patterns by weakening the impulsive system while strengthening the reflective system. TRIAL REGISTRATION: clinicaltrials.gov: NCT02372318.

Colocalization analysis of pancreas eQTLs with risk loci from alcoholic and novel non-alcoholic chronic pancreatitis GWAS suggests potential disease causing mechanisms.

BACKGROUND: Previous genome-wide association studies (GWAS) identified genome-wide significant risk loci in chronic pancreatitis and investigated underlying disease causing mechanisms by simple overlaps with expression quantitative trait loci (eQTLs), a procedure which may often result in false positive conclusions. METHODS: We conducted a GWAS in 584 non-alcoholic chronic pancreatitis (NACP) patients and 6040 healthy controls. Next, we applied Bayesian colocalization analysis of identified genome-wide significant risk loci from both, our recently published alcoholic chronic pancreatitis (ACP) and the novel NACP dataset, with pancreas eQTLs from the GTEx V8 European cohort to prioritize candidate causal genes and extracted credible sets of shared causal variants. RESULTS: Variants at the CTRC (p = 1.22 × 10-21) and SPINK1 (p = 6.59 × 10-47) risk loci reached genome-wide significance in NACP. CTRC risk variants colocalized with CTRC eQTLs in ACP (PP4 = 0.99, PP4/PP3 = 95.51) and NACP (PP4 = 0.99, PP4/PP3 = 95.46). For both diseases, the 95% credible set of shared causal variants consisted of rs497078 and rs545634. CLDN2-MORC4 risk variants colocalized with CLDN2 eQTLs in ACP (PP4 = 0.98, PP4/PP3 = 42.20) and NACP (PP4 = 0.67, PP4/PP3 = 7.18), probably driven by the shared causal variant rs12688220. CONCLUSIONS: A shared causal CTRC risk variant might unfold its pathogenic effect in ACP and NACP by reducing CTRC expression, while the CLDN2-MORC4 shared causal variant rs12688220 may modify ACP and NACP risk by increasing CLDN2 expression.

Examining a brief measure and observed cutoff scores to identify reward and relief drinking profiles: Psychometric properties and pharmacotherapy response.

BACKGROUND: Precision medicine approaches attempt to reduce variability in alcohol use disorder (AUD) outcomes by identifying patient characteristics that predict response to a particular treatment. Recent work has examined the extent to which individuals with AUD may seek alcohol to enhance positive experiences (reward drinking) or relieve negative states (relief drinking) and shown that a high reward/low relief phenotype predicts naltrexone treatment response. Yet, limitations of reward/relief drinking measures may hamper efforts to translate findings to clinical practice. We sought to refine a brief measure of reward/relief drinking and develop cutoff scores to identify reward/relief subgroups that predict pharmacotherapy response. METHODS: The Inventory of Drinking Situations (IDS), used in previous studies to measure reward/relief drinking, was administered to 426 participants (77% male; average age = 45.3) in a clinical trial examining naltrexone and acamprosate. RESULTS: Item response theory and tests of differential item functioning across sex, age, and alcohol dependence severity were used to create a 10-item measure, titled the Reward and Relief IDS (RR-IDS). Cutoff scores on the RR-IDS for the reward/relief drinking subgroups were identified using latent profile and area under the curve analyses. The cutoff scores demonstrated good construct validity. Individuals in the high reward/low relief subgroup who received naltrexone or acamprosate had a decreased likelihood of heavy drinking (large effect sizes) versus those who received placebo. CONCLUSIONS: The RR-IDS is a practical measure for identifying reward/relief subgroups and predicting pharmacotherapy response. Pending replication of these findings, the RR-IDS could be a critical precision medicine tool for prescribing AUD medications.

Association Between Functional and Structural Brain Connectivity of the Default Mode Network in Non-treatment Seeking Individuals With Alcohol Use Disorder.

AIMS: Alcohol use disorder (AUD) is associated with alterations within the default mode network (DMN) at rest. Also, impaired white matter structures have been observed in individuals with AUD. This study developed a workflow for examining the relation between functional and structural connectivity, exemplary for nodes of the DMN within a sample of non-treatment seeking individuals with AUD. Furthermore, AUD severity was correlated with both measures independently. METHODS: The functional magnetic resonance imaging (fMRI) protocol included anatomical, resting state and diffusion weighted imaging measurements. Independent component analyses and deterministic fiber tracking as well as correlation analyses, including the severity of AUD, were performed. N = 18 out of 23 adult study participants took part in the fMRI examination, and N = 15 were included in the final analyses. RESULTS: Established resting-state networks were reliably identified in our sample. Structural connections were found between several nodes of the DMN, whereas only fibers between the medial prefrontal cortex and the posterior cingulate cortex were reliably detected in all individuals. A negative correlation was observed between brain activation during rest and AUD severity in left parietal and temporal regions and the putamen. A more severe AUD predicted impairments in white matter integrity of the cingulum. CONCLUSION: In AUD, information obtained from a combination of resting-state, diffusion weighted data and clinical information has great potential to provide a more profound understanding of the disorder since alterations may already become apparent at earlier stages of the disorder, e.g. in non-treatment seeking individuals. SUMMARY: Alcohol use disorder leads to alterations in the default mode network of the resting brain that is associated with the severity of the disorder. Following our workflow, white matter impairments can be observed between some of the nodes of the default mode network using diffusion tensor imaging. Both, resting-state functional and structural connectivity relate to the severity of alcohol use disorder.

Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study.

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥ 5 drinks for men, ≥4 drinks for women in a day), during the first 3 months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N = 1083 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p = 1.6E-8) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p = 3.9E-8; acamprosate TR: rs77583603, p = 3.1E-9). The top association signal for TR (p = 7.7E-8) and second strongest signal in the THR (p = 6.1E-8) analysis of naltrexone-treated patients maps to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p = 3.7E-4) and THR (p = 2.6E-4). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.

Nalmefene attenuates neural alcohol cue-reactivity in the ventral striatum and subjective alcohol craving in patients with alcohol use disorder.

RATIONALE: Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available. OBJECTIVES: We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving. METHODS: Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues. RESULTS: An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo. CONCLUSION: In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.

FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17-46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02-0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

Reward drinking and naltrexone treatment response among young adult heavy drinkers.

AIMS: Theory-driven, exploratory study to: (i) identify a reward drinking phenotype in young adults; (ii) evaluate this phenotype as a predictor of naltrexone response; and (iii) examine mechanisms of naltrexone in reward drinkers. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: USA. PARTICIPANTS: A total of 128 young adult (ages 18-25) heavy drinkers. INTERVENTIONS: Naltrexone versus placebo. MEASUREMENTS: Daily surveys assessed affect, urge, drinking, and context. The Drinking Motives Questionnaire was used to identify phenotypes based on reward (enhancement motives) and relief (coping motives) drinking. FINDINGS: We identified three profiles: "Low reward/Low relief" (14.1%; low enhancement/low coping motives); "Reward drinkers" (62.2%; high enhancement/low coping motives); and "High reward/High relief" (22.7%; high enhancement/high coping motives). Among reward drinkers (versus low profile), naltrexone significantly reduced percent days drinking to intoxication (blood alcohol concentration [BAC] ≥0.08) (PDI) (d = 0.56; 95% CI [0.17, 0.96]) and percent high intensity drinking days (PHID) (8/10 drinks for women/men) (d = 0.32; 95% CI [0.01, 0.68]). Among the high reward/high relief profile drinkers (versus low profile), naltrexone reduced PHID (d = 0.69; 95% CI [0.02, 1.50]). Using profile-informed cutoffs and observed scores (for clinical applicability): (i) among cutoff-derived reward drinkers, we found a medium-to-large (d = 0.66; 95% CI [0.24, 1.16]) and small effect (d = 0.28; 95% CI [0.04, 0.72]) of naltrexone in reducing PDI and PHID, respectively; and (ii) among the cutoff-derived high reward/high relief subgroup, we found a medium-to-large effect (d = 0.63; 95% CI [0.05, 1.1]) of naltrexone in reducing PHID. Among reward drinkers (not other profiles), naltrexone reduced drinking on days a drinking event occurred by weakening the within-day association between positive affect and urges (P < 0.05). CONCLUSIONS: Naltrexone has pronounced effects in reducing risky drinking among young adult reward drinkers (high reward/low relief) by reducing urges on days when individuals have higher positive affect and are exposed to a drinking event. Naltrexone also appears to reduce risky drinking among young adult high reward/high relief drinkers, but not via the same mechanism.

The World Health Organization Risk Drinking Levels Measure of Alcohol Consumption: Prevalence and Health Correlates in Nationally Representative Surveys of U.S. Adults, 2001-2002 and 2012-2013.

OBJECTIVE: Little is known about change over time in the prevalence of World Health Organization (WHO) risk drinking levels (very high, high, moderate, low) and their association with health conditions, overall and by gender. The authors used two sets of nationally representative U.S. survey data to determine whether changes over time varied by gender and to examine whether health conditions related to alcohol were associated with WHO risk drinking level within each survey, and whether these associations differed by gender. METHODS: Data on current drinkers from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N=26,655) and the 2012-2013 NESARC-III (N=25,659) were analyzed using logistic regression. Prevalence differences between surveys were estimated for each drinking level overall and by gender. Within each survey, prevalence differences by WHO risk drinking level were estimated for alcohol use disorder (AUD), drug use disorders, functional impairment, liver disease, and depressive and anxiety disorders. RESULTS: In the 2012-2013 survey, the prevalences of moderate, high, and very high risk drinking were 5.9%, 3.2%, and 3.5%, respectively, representing significant increases from the prevalences in the 2001-2002 survey, which were 1.0%, 0.6%, and 0.9%, respectively. The increase for very high risk drinking among men (0.5%) was smaller than the increase among women (1.4%). Within both surveys, compared with low risk, health conditions were significantly associated with very high risk (range of prevalence differences, 2.2%-57.8%), high risk (2.6%-41.3%), and moderate risk (0.6%-29.8%) drinking. Associations were similar by gender, except that there were stronger effects for AUD in men and for functional impairment and depressive and anxiety disorders in women. CONCLUSIONS: The increase in potentially problematic drinking levels among U.S. adults emphasizes the need for better prevention and treatment strategies. The study results support the validity of the WHO risk drinking levels, which show clinical utility as nonabstinent drinking reduction treatment goals. Such goals could engage more people in treatment, improving public health by decreasing personal and societal consequences of risk drinking.

Comparison of European Clinical Guidelines on the Management of Alcohol Use Disorders.

BACKGROUND: Alcohol is a leading cause of morbidity and mortality in the European region, and tackling the harmful use of alcohol is a public health priority. Most countries in the region have national strategies for treating alcohol use disorders (AUD), but there is significant between-country variation. OBJECTIVES: This study aimed to compare clinical guidelines for the management of AUD from countries of the European region and to determine whether countries' relative wealth or quality of their health systems had affected the guidelines. METHODS: A survey was conducted of 24 countries. The survey encompassed how AUD clinical guidelines were researched, the range and expertise of contributors, which topics of AUD treatment were included, the definition of a "standard drink" used, and the publishing, funding, endorsement, and dissemination of the guideline. RESULTS: Twenty-one of the 24 countries surveyed had a clinical guideline for AUD. All guidelines were underpinned by a literature review, and psychiatrists were the professional group most commonly involved in producing them. Most of the guidelines covered typical cornerstones of AUD care such as treatment of alcohol dependence, pharmacotherapy for relapse prevention, and detoxification. Definitions of a "standard drink" ranged from 8 to 20 grams of ethanol. Governments or governmental bodies were the main publishers and funders of guidelines, and the vast majority of guidelines were freely available online. There were no statistically significant effects of GDP, GDP per capita, or World Health Organization's World Health Report rankings on whether countries were more likely to have an AUD clinical guideline, to have performed a systematic literature review, or to have involved service users in producing their guideline. CONCLUSIONS: The results of this survey reflect widespread good practice in producing AUD clinical guidelines across European countries. Regional research collaborations could offer significant time and cost savings in producing the evidence base from which guidelines are then written.

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.