Margaret E. Mattson

Early Developmental Processes and the Continuity of Risk for Underage Drinking and Problem Drinking

Developmental pathways to underage drinking emerge before the second decade of life. Many scientists, however, as well as the general public, continue to focus on proximal influences surrounding the initiation of drinking in adolescence, such as social, behavioral, and genetic variables related to availability and ease of acquisition of the drug, social reinforcement for its use, and individual differences in drug responses. In the past 20 years, a considerable body of evidence has accumulated on the early (often much earlier than the time of the first drink) predictors and pathways of youthful alcohol use and abuse. These early developmental influences involve numerous risk, vulnerability, promotive, and protective processes. Some of these factors are not related directly to alcohol use, whereas others involve learning and expectancies about later drug use that are shaped by social experience. The salience of these factors (identifiable in early childhood) for understanding the course and development of adult alcohol and other drug use disorders is evident from the large and growing body of findings on their ability to predict adult clinical outcomes. This review summarizes the evidence on early pathways toward and away from underage drinking, with a particular focus on the risk and protective factors and the mediators and moderators of risk for underage drinking that become evident during the preschool and early school years. It is guided by a developmental perspective on the aggregation of risk and protection and examines the contributions of biological, psychological, and social processes within the context of normal development. Implications of this evidence for policy, intervention, and future research are discussed.

National Estimates of Marijuana Use and Related Indicators — National Survey on Drug Use and Health, United States, 2002–2014

PROBLEM/CONDITION In the United States, marijuana is the most commonly used illicit drug. In 2013, 7.5% (19.8 million) of the U.S. population aged ≥12 years reported using marijuana during the preceding month. Because of certain state-level policies that have legalized marijuana for medical or recreational use, population-based data on marijuana use and other related indicators are needed to help monitor behavioral health changes in the United States. PERIOD COVERED 2002-2014. DESCRIPTION OF SYSTEM The National Survey on Drug Use and Health (NSDUH) is a national- and state-level survey of a representative sample of the civilian, noninstitutionalized U.S. population aged ≥12 years. NSDUH collects information about the use of illicit drugs, alcohol, and tobacco; initiation of substance use; frequency of substance use; substance dependence and abuse; perception of substance harm risk or no risk; and other related behavioral health indicators. This report describes national trends for selected marijuana use and related indicators, including prevalence of marijuana use; initiation; perception of harm risk, approval, and attitudes; perception of availability and mode of acquisition; dependence and abuse; and perception of legal penalty for marijuana possession. RESULTS In 2014, a total of 2.5 million persons aged ≥12 years had used marijuana for the first time during the preceding 12 months, an average of approximately 7,000 new users each day. During 2002-2014, the prevalence of marijuana use during the past month, past year, and daily or almost daily increased among persons aged ≥18 years, but not among those aged 12-17 years. Among persons aged ≥12 years, the prevalence of perceived great risk from smoking marijuana once or twice a week and once a month decreased and the prevalence of perceived no risk increased. The prevalence of past year marijuana dependence and abuse decreased, except among persons aged ≥26 years. Among persons aged ≥12 years, the percentage reporting that marijuana was fairly easy or very easy to obtain increased. The percentage of persons aged ≥12 reporting the mode of acquisition of marijuana was buying it and growing it increased versus getting it for free and sharing it. The percentage of persons aged ≥12 years reporting that the perceived maximum legal penalty for the possession of an ounce or less of marijuana in their state is a fine and no penalty increased versus probation, community service, possible prison sentence, and mandatory prison sentence. INTERPRETATION Since 2002, marijuana use in the United States has increased among persons aged ≥18 years, but not among those aged 12-17 years. A decrease in the perception of great risk from smoking marijuana combined with increases in the perception of availability (i.e., fairly easy or very easy to obtain marijuana) and fewer punitive legal penalties (e.g., no penalty) for the possession of marijuana for personal use might play a role in increased use among adults. PUBLIC HEALTH ACTION National- and state-level data can help federal, state, and local public health officials develop targeted prevention activities to reduce youth initiation of marijuana use, prevent marijuana dependence and abuse, and prevent adverse health effects. As state-level laws on medical and recreational marijuana use change, modifications might be needed to national- and state-level surveys and more timely and comprehensive surveillance systems might be necessary to provide these data. Marijuana use in younger age groups is a particular public health concern, and changing the perception of harm risk from smoking marijuana is needed.

A Double-Blind, Placebo-Controlled Trial to Assess the Efficacy of Quetiapine Fumarate XR in Very Heavy-Drinking Alcohol-Dependent Patients

BACKGROUND Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol-dependent population of very heavy drinkers. METHODS In this double-blind, placebo-controlled trial, 224 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization. RESULTS No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy-drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%). CONCLUSIONS This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy-drinking alcohol-dependent patients.

A Double‐Blind, Placebo‐Controlled Trial Assessing the Efficacy of Levetiracetam Extended‐Release in Very Heavy Drinking Alcohol‐Dependent Patients

BACKGROUND Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers. METHODS In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16. RESULTS No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001). CONCLUSIONS This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.

Evaluation Plan for the Community Intervention Trial for Smoking Cessation (COMMIT).

The National Cancer Institute is sponsoring the Community Intervention Trial for Smoking Cessation (COMMIT), a multi-center research project designed to test the value of a community-based effort to promote smoking cessation. The trial involves eleven matched pairs of communities with random assignment of one community per pair to the intervention or to the comparison condition. This article reviews the rationale and methodology of the COMMIT evaluation plan which is organized into four components: 1) outcome assessment, monitoring changes in community smoking patterns; 2) impact assessment, measuring the effect of the COMMIT intervention on mediating factors thought to be important in facilitating changes in community smoking behavior (e.g., social norms supporting nonsmoking); 3) process assessment, monitoring the quality and timeliness of intervention delivery; and 4) economic assessment, estimating the cost effectiveness of the intervention.

Cigarette Smoking Predicts Differential Benefit from Naltrexone for Alcohol Dependence

BACKGROUND Identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. Cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. Nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. METHODS We examined the association between cigarette smoking and drinking outcomes in the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management, combined behavioral therapy) in 1383 alcohol-dependent individuals. RESULTS Smokers (i.e., more than one half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. However, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. This pattern of findings occurred independent of whether patients received combined behavioral intervention or medical management and remained after controlling for alcoholism typology and baseline demographic differences. Approximately 9% of smokers quit smoking, and an additional 10% reduced their cigarette intake during treatment. Reductions in smoking did not vary by treatment assignment. CONCLUSIONS These results suggest that naltrexone might be particularly beneficial for improving alcohol use outcomes in alcohol-dependent smokers.

Development of medications for alcohol use disorders: recent advances and ongoing challenges.

During the past decade, efforts to develop medications for alcoholism have burgeoned. Three agents, disulfiram, naltrexone and acamprosate, are now approved in a large number of countries. Although many patients have benefited from existing medications, their effects are moderate, and some alcoholics fail to respond to them. A host of new agents are currently under active investigation. Critical barriers must be overcome to ensure that future efforts in the development of medications for alcohol use disorders reach full fruition. These challenges include: establishing key targets for drug discovery; validating animal and human screening models; and developing biomarkers to help predict treatment success. In addition, it is important to formulate methodological and statistical strategies to efficiently conduct alcohol pharmacotherapy trials; to specify genetic and phenotypic patient characteristics associated with efficacy and safety for lead compounds; to forge productive alliances among governmental agencies, the pharmaceutical industry and academic researchers to further drug development; and, ultimately and perhaps most difficult, to engage the practitioner community to incorporate medications into the alcohol treatment process.

Binge drinking and the risk of suicidal thoughts, plans, and attempts

BACKGROUND Major depression is one of the strongest known risk factors for suicide. However, of the estimated 8.5 million adults with serious thoughts of suicide in the past year, only half had a major depressive episode (MDE). Identifying risk factors for suicide in the absence of depression may provide additional targets for prevention and intervention. This study uses nationally representative data to evaluate the association of binge drinking with suicidal thoughts, plans, and attempts in adults with and without MDE. METHODS Combined 2008-2012 National Survey on Drug Use and Health data were analyzed. Sex-stratified prevalence estimates of past year suicide indicators were generated by past month binge drinking and past year MDE status. Logistic regression was used to evaluate the association of binge drinking with suicide indicators by sex with and without MDE. RESULTS Unadjusted prevalence estimates for suicide indicators in males and females were higher among binge drinkers than among nonbinge drinkers, regardless of MDE status. Regression analyses indicated that binge drinking was associated with suicidal thoughts (adjusted odds ratio [aOR]=1.51, 95% confidence interval [CI]=1.28-1.79), plans (aOR=1.75, CI=1.23-2.48), and attempts (aOR=2.57, CI=1.74-3.79) in females without MDE and with suicidal thoughts in males without MDE (aOR=1.25, CI=1.04-1.49). Among males and females with MDE, binge drinking was not associated with any of the suicide indicators (p>.05). CONCLUSIONS Binge drinking in females without MDE may be an indicator for identifying at risk individuals for targeting suicide prevention activities.

Developments in alcoholism treatment research: Patient-treatment matching

This article describes patient-treatment matching, a recent advance in alcoholism treatment research. A general description of the concept is presented and the challenges patient-treatment matching poses for investigators and for treatment providers are described. Project MATCH, a multisite clinical trial designed to test the matching hypothesis is used to illustrate approaches to addressing the research challenge. Two additional avenues of promising patient-treatment matching research, one relating to patient characteristics and the other to pharmacological treatments, are also summarized. The article concludes with a brief prescription for individual providers to implement and test treatment matching strategies in their own clinical practice.

Psychometric instruments to assist in alcoholism treatment planning

The clinical practice of alcoholism treatment can be enhanced by the judicious use of standardized psychometric instruments to characterize clients during the course of treatment. Knowledge of key behavioral, personality, and alcohol-specific factors will increase the clinicians ability to select the most appropriate treatment option, or, even if treatment options are limited, at least to develop a treatment plant with the patients unique needs in mind. Monitoring of progress towards treatment goals can also be facilitated by the use of selected assessment tools. Seven examples of well-validated instruments are discussed, with suggestions on how data derived from them may be applied in the treatment planning process.