Pharmacotherapy For Alcohol Use Disorder Research Articles

Mecamylamine treatment for alcohol dependence: a randomized controlled trial.

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects. Out-patient, randomized, double-blind clinical trial for 12weeks of treatment with mecamylamine (10mg) (n=65) versus placebo (n=63). Connecticut, USA. Individuals had current alcohol dependence (n=128), had an average age of 48.5 [standard deviation (SD)=9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non-smokers (42.2%). Participants were randomized to mecamylamine 10mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel. Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects. There were no significant differences in the percentage of heavy drinking days at 3months between the mecamylamine (mean=18.4, SD=29.0) and placebo treatment groups (mean=20.4, SD=29.2) [F1, 100 =1.3, P=0.25; effect size d=0.07; mean difference=2.06, 95% confidence interval (CI)=-8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions. Mecamylamine 10mg per day did not reduce alcohol consumption significantly in treatment-seeking smokers and non-smokers with alcohol use disorder.

Variation in receipt of pharmacotherapy for alcohol use disorders across racial/ethnic groups: A national study in the U.S. Veterans Health Administration

ObjectivePharmacologic treatment is recommended for alcohol use disorders (AUD), but most patients do not receive it. Although racial/ethnic minorities have greater AUD consequences than whites, whether AUD medication receipt varies across race/ethnicity is unknown. We evaluate this in a national sample. MethodsElectronic health records data were extracted for all black, Hispanic, and/or white patients who received care at the U.S. Veterans Health Administration (VA) during Fiscal Year 2012 and had a documented AUD diagnosis. Mixed effects regression models, with a random effect for facility, determined the likelihood of receiving AUD pharmacotherapy (acamprosate, disulfiram, topirimate or oral or injectable naltrexone ≤180days after AUD diagnosis) for black and Hispanic patients relative to white patients. Models were unadjusted and then adjusted for patient- and facility-level factors. Results297,506 patients had AUD; 26.4% were black patients, 7.1% were Hispanic patients and 66.5% were white patients; 5.1% received AUD medications. Before adjustment, black patients were less likely than white [Odds Ratio (OR) 0.77; 95% Confidence Interval (CI) 0.75 −0.82; (p<0.001)], while Hispanic patients were more likely than white (OR 1.09; 95% CI 1.01–1.16) to receive AUD medications. After adjustment, black patients remained less likely than white to receive AUD medications (OR 0.68; 95% CI 0.65–0.71; p<0.0001); no difference between Hispanic and white patients was observed (OR 0.94; 95% CI 0.87–1.00; p=0.07). ConclusionsIn this national study of patients with AUD, blacks were less likely to receive AUD medications than whites. Future research is needed to identify why these disparities exist.

Disparities in pharmacotherapy for alcohol use disorder in the context of universal health care: a Swedish register study.

Pharmacotherapy can be an important part of the continuum of care for alcohol use disorder (AUD). The Swedish universal health-care system emphasizes provision of care to marginalized groups. The primary aim was to test associations of neighborhood deprivation and disadvantaged social status with receipt of AUD pharmacotherapy in this context. Data from linked population registers were used to follow an open cohort over 7years. Sweden. Alcohol-related ICD-10 codes reported for all hospitalizations in the Swedish Hospital Discharge Register and all clinic/office visits in the Outpatient Care Register between 2005 and 2012 were used to identify 62 549 cases with AUD. The primary outcome was any AUD pharmacotherapy (naltrexone, disulfiram, acamprosate, nalmefene) picked up by patients between 2005 and 2012 (versus none), based on the Swedish Prescribed Drug Register. Neighborhood deprivation was defined using aggregated data from the Total Population Register; indicators of disadvantaged social status (income, education, country of origin) also came from this source. Approximately half the cases (53.7%) picked up one or more AUD pharmacotherapy prescriptions. In adjusted models, people living in neighborhoods with moderate [odds ratio (OR)=0.90, 95% confidence interval (CI)=0.86, 0.95] or high levels of deprivation (OR=0.75, 95% CI=0.70, 0.79) compared with low deprivation, those with lower incomes (for example, lowest quartile: OR=0.70, 95% CI=0.66, 0.73 compared with highest) and less education (for example, <10years: OR=0.82, 95% CI=0.78, 0.85 compared with 12+ years) and people born outside Sweden (OR=0.74, 95% CI=0.71, 0.78 compared with Swedish-born) were significantly less likely to pick up a prescription for AUD pharmacotherapy during the study period. There appear to be socio-economic disparities in the receipt of pharmacotherapy for alcohol use disorder in Sweden.

Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder.

Barriers to and facilitators of pharmacotherapy for alcohol use disorder in VA residential treatment programs

Among US military veterans, alcohol use disorder (AUD) is prevalent and in severe cases patients need intensive AUD treatment beyond outpatient care. The Department of Veterans Affairs (VA) delivers intensive, highly structured addiction and psychosocial treatment through residential programs. Despite the evidence supporting pharmacotherapy among the effective treatments for AUD, receipt of these medications (e.g., naltrexone, acamprosate) among patients in residential treatment programs varies widely. In order to better understand this variation, the current study examined barriers and facilitators to use of pharmacotherapy for AUD among patients in VA residential treatment programs. Semi-structured qualitative interviews with residential program management and staff were conducted and the Consolidated Framework for Implementation Research was used to guide coding and analysis of interview transcripts. Barriers to use of pharmacotherapy for AUD included cultural norms or philosophy against prescribing, lack of access to willing prescribers, lack of interest from leadership, and perceived lack of patient interest or need. Facilitators included cultural norms of openness or active promotion of pharmacotherapy; education for patients, program staff and prescribers; having prescribers on staff, and care coordination within residential treatment and with other clinic settings in and outside VA. Developing and testing improvement strategies to increase care coordination and consistent support from leadership may also yield increases in the use of pharmacotherapy for AUD among residential patients.

Pharmacotherapy for Alcohol Use Disorders: Physicians' Perceptions and Practices.

Alcohol use disorders (AUDs) are an important cause of morbidity and mortality. Despite the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommendations that medications be considered for patients with alcohol dependence, the mainstay of treatment has been counseling. We designed a survey to assess the treatment practices of psychiatrists and family medicine (FM) physicians in an effort to identify barriers to the use of pharmacotherapy and develop strategies to increase physician knowledge and utilization of these medications. An anonymous online survey was sent to FM physicians and psychiatrists nationwide. The survey collected demographic information and assessed prescription of medications in treating AUDs, including FDA-approved medications and other medications used off-label for this purpose. We also examined factors that would lead to an increase in AUDs pharmacotherapy. A total of 491 surveys were completed, with 475 responses included in the final analyses. 45.5% of participants were psychiatrists vs. 54.5% FM physicians. The 74.7% respondents had used medications to treat AUDs, with psychiatrists more likely to have prescribed acamprosate, naltrexone, and several off-label medications. FM physicians were more likely to report efficacy concerns. A majority of all physicians sampled would increase pharmacotherapy of AUDs with increased training. In our sample, most physicians have used medications to treat AUDs. There were concerns about efficacy with all non-FDA-approved medications, but limited treatment success even with FDA-approved medications. Greater education about pharmacotherapy, including predictors for treatment response amongst patients, should help alleviate some of the uncertainties reported with medications' efficacy and lead to a more individualized treatment approach.

Binge Ethanol Consumption Increases Inflammatory Pain Responses and Mechanical and Cold Sensitivity: Tigecycline Treatment Efficacy Shows Sex Differences.

BackgroundPhysicians have long reported that patients with chronic pain show higher tendencies for alcohol use disorder (AUD), and AUD patients appear to have higher pain sensitivities. The goal of this study was to test 2 hypotheses: (i) binge alcohol consumption increases inflammatory pain and mechanical and cold sensitivities; and (ii) tigecycline is an effective treatment for alcohol‐mediated‐increased pain behaviors and sensitivities. Both female and male mice were used to test the additional hypothesis that important sex differences in the ethanol (EtOH)‐related traits would be seen.Methods“Drinking in the Dark” (DID) alcohol consuming and nondrinking control, female and male, adult C57BL/6J mice were evaluated for inflammatory pain behaviors and for the presence of mechanical and cold sensitivities. Inflammatory pain was produced by intraplantar injection of formalin (10 μl, 2.5% in saline). For cold sensation, a 20 μl acetone drop was used. Mechanical withdrawal threshold was measured by an electronic von Frey anesthesiometer. Efficacy of tigecycline (80 mg/kg i.p.) to reduce DID‐related pain responses and sensitivity was tested.Results DID EtOH consumption increased inflammatory pain behavior, while it also produced sustained mechanical and cold sensitivities in both females and males. Tigecycline produced antinociceptive effects in males; a pro‐nociceptive effect was seen in females in the formalin test. Likewise, the drug reduced both mechanical and cold sensitivities in males, but females showed an increase in sensitivity in both tests.ConclusionsOur results demonstrated that binge drinking increases pain, touch, and thermal sensations in both sexes. In addition, we have identified sex‐specific effects of tigecycline on inflammatory pain, as well as mechanical and cold sensitivities. The development of tigecycline as an AUD pharmacotherapy may need consideration of its pro‐nociceptive action in females. Further studies are needed to investigate the mechanism underlying the sex‐specific differences in nociception.

Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity.

Pharmacogenetic studies of alcohol use disorder (AUD) have suggested that the efficacy of treatments for AUD is, in part, influenced by the genetic background of an individual. Since the frequency of alleles associated with pharmacotherapy for AUD varies by ancestral background, the effectiveness of medications used to treat AUD may vary among different populations. The purpose of this review is to summarize the existing pharmacogenetic studies of treatments for AUD in individuals of European, East Asian, African, and American Indian/Alaska Native ancestry. Electronic databases were searched for pharmacogenetic studies of AUD treatment that included individuals of diverse ancestral backgrounds. Pharmacogenetic studies of AUD reviewed here have primarily investigated genetic variation thought to play a role in the response to naltrexone, ondansetron, and topiramate. There is support that the A118G polymorphism should be further investigated in individuals of East Asian ancestry. Given the lack of pharmacogenetic research on response to AUD medication in ethnic minority populations and the mixed results, there is a critical need for future studies among individuals of different ancestries. More efforts should be devoted to standardizing procedures such that results can be more readily integrated into a body of literature that can directly inform clinical practice. This review highlights the importance for future research to aim for inclusiveness in pharmacogenetic studies of AUD and increase diversity of clinical trials in order to provide the best treatment outcomes for individuals across different racial and ethnic groups. (Am J Addict 2017;26:516-525).

Exposure-Response Relationships during Free-Access Intravenous Alcohol Self-Administration in Nondependent Drinkers: Influence of Alcohol Expectancies and Impulsivity.

Background:Self-administration is a hallmark of all addictive drugs, including alcohol. Human laboratory models of alcohol self-administration have characterized alcohol-seeking behavior and served as surrogate measures of the effectiveness of pharmacotherapies for alcohol use disorders. Intravenous alcohol self-administration is a novel method that assesses alcohol exposure driven primarily by the pharmacological response to alcohol and may have utility in characterizing unique behavioral and personality correlates of alcohol-seeking and consumption.Methods:This study examined exposure-response relationships for i.v. alcohol self-administration, and the influence of impulsivity and alcohol expectancy, in healthy, nondependent drinkers (n=112). Participants underwent a 2.5-hour free-access i.v. alcohol self-administration session using the Computerized Alcohol Infusion System. Serial subjective response measures included the Drug Effects Questionnaire and Alcohol Urge Questionnaire. To characterize the motivational aspects of alcohol consumption prior to potential acute adaptation, the number of self-infusions in the first 30 minutes of the free-access session was used to classify participants as low- and high-responders.Results:High-responders showed greater subjective responses during i.v. alcohol self-administration compared with low responders, reflecting robust exposure-driven hedonic responses to alcohol. High-responders also reported heavier drinking patterns and lower scores for negative alcohol expectancies on the Alcohol Effects Questionnaire. High-responders also showed higher measures of impulsivity on a delayed discounting task, supporting previous work associating impulsivity with greater alcohol use and problems.Conclusions:These findings indicate that early-phase measures of free-access i.v. alcohol self-administration are particularly sensitive to the rewarding and motivational properties of alcohol and may provide a unique phenotypic marker of alcohol-seeking behavior.

Multifaceted academic detailing program to increase pharmacotherapy for alcohol use disorder: interrupted time series evaluation of effectiveness.

BackgroundActive consideration of effective medications to treat alcohol use disorder (AUD) is a consensus standard of care, yet knowledge and use of these medications are very low across diverse settings. This study evaluated the overall effectiveness a multifaceted academic detailing program to address this persistent quality problem in the US Veterans Health Administration (VHA), as well as the context and process factors that explained variation in effectiveness across sites.MethodsAn interrupted time series design, analyzed with mixed-effects segmented logistic regression, was used to evaluate changes in level and rate of change in the monthly percent of patients with a clinically documented AUD who received naltrexone, acamprosate, disulfiram, or topiramate. Using data from a 20 month post-implementation period, intervention sites (n = 37) were compared to their own 16 month pre-implementation performance and separately to the rest of VHA.ResultsFrom immediately pre-intervention to the end of the observation period, the percent of patients in the intervention sites with AUD who received medication increased over 3.4 % in absolute terms and 68 % in relative terms (i.e., 4.9–8.3 %). This change was significant compared to the pre-implementation period in the intervention sites and secular trends in control sites. Sites with lower pre-implementation adoption, more person hours of detailing, but fewer people detailed, had larger immediate increases in medication receipt after implementation. The average number of detailing encounters per person was associated with steeper increases in slope over time.ConclusionsThis study found empirical support for a multifaceted quality improvement strategy aimed at increasing access to and utilization of pharmacotherapy for AUD. Future studies should focus on determining how to enhance the programs effects, especially in non-responsive locations.

Primary Care Providers' Interest in Using a Genetic Test to Guide Alcohol Use Disorder Treatment

BackgroundEfforts to identify genetic moderators of pharmacotherapy response have generated interest in clinical applications of pharmacogenetic tests in alcohol use disorder (AUD) treatment. To date, no research on providers' interest in using pharmacogenetic tests in the context of AUD treatment has been reported. We conducted qualitative interviews with primary care providers from 5 clinics in the Veterans Health Administration (VA) to assess their interest in using a hypothetical genetic test to inform treatment of AUD with pharmacotherapy. MethodsKey contacts were used to recruit 24 providers from 5 primary care clinics associated with a single large VA medical facility. Participants completed 30-minute in-person semi-structured interviews focused on barriers and facilitators to provision of pharmacotherapy for AUD. Interviews included a hypothetical scenario regarding the availability of a genetic test to inform AUD pharmacotherapy provision and/or selection. Provider responses to the hypothetical scenario were recorded, transcribed and analyzed qualitatively using inductive content analysis. Data were independently coded by three investigators, and themes were identified via consensus. ResultsParticipants were generally interested in a genetic test to aid in AUD treatment planning. Five common themes were identified, including: perceived benefits of a pharmacogenetic test (e.g., aiding with therapeutic choice, positively impacting patient motivation for and engagement with AUD treatment), perceived drawbacks (e.g., limiting potential benefits of pharmacotherapy by reducing the target population for its receipt, adverse impacts of “negative” results), caveats to clinical utility (e.g., utility would depend on prognostic accuracy and/or medication characteristics), uncertainty as to whether such a test would impact clinical decision-making, and pragmatic barriers to use (costs and other resources, such as laboratory facilities). ConclusionsPrimary care providers in this study generally believed a genetic test to aid in AUD treatment planning would be useful, due to its potential to hone treatment choice as well as to influence patient motivation and adherence to treatment. However, providers acknowledged that a test's utility would depend on the strength of its prognostic characteristics, its other benefits relative to standard care, and lack of pragmatic barriers.

Heavy-Drinking Smokers: Pathophysiology and Pharmacologic Treatment Options

Heavy-Drinking Smokers: Pathophysiology and Pharmacologic Treatment Options

Specifying and Pilot Testing Quality Measures for the American Society of Addiction Medicine's Standards of Care.

In 2013, the American Society of Addiction Medicine (ASAM) approved its Standards of Care for the Addiction Specialist Physician. Subsequently, an ASAM Performance Measures Panel identified and prioritized the standards to be operationalized into performance measures. The goal of this study is to describe the process of operationalizing 3 of these standards into quality measures, and to present the initial measure specifications and results of pilot testing these measures in a large health care system. By presenting the process rather than just the end results, we hope to shed light on the measure development process to educate, and also to stimulate debate about the decisions that were made. Each measure was decomposed into major concepts. Then each concept was operationalized using commonly available administrative data sources. Alternative specifications examined and sensitivity analyses were conducted to inform decisions that balanced accuracy, clinical nuance, and simplicity. Using data from the US Veterans Health Administration (VHA), overall performance and variation in performance across 119 VHA facilities were calculated. Three measures were operationalized and pilot tested: pharmacotherapy for alcohol use disorder, pharmacotherapy for opioid use disorder, and timely follow-up after medically managed withdrawal (aka detoxification). Each measure was calculable with available data, and showed ample room for improvement (no ceiling effects) and wide facility-level variability. Next steps include conducting feasibility and pilot testing in other health care systems and other contexts such as standalone addiction treatment programs, and also to study the specification and predictive validity of these measures.

Receipt of Pharmacotherapy for Alcohol Use Disorder by Male Justice-Involved U.S. Veterans Health Administration Patients.

This study examined whether, among Veterans Health Administration (VHA) patients, veterans with recent or current justice involvement have equal receipt of pharmacotherapy for alcohol use disorder compared to veterans with no justice involvement. Using national VHA records, we calculated the overall and facility rates of receipt as the number of patients who received pharmacotherapy for alcohol use disorder divided by the number of patients diagnosed with an alcohol use disorder. Using a mixed-effects logistic regression model, we tested whether justice involvement was associated with pharmacotherapy receipt. Male veterans with jail/court involvement had significantly higher odds of receiving pharmacotherapy for alcohol use disorder compared to other male veterans. Justice-involved veterans had equal or better receipt of pharmacotherapy for alcohol use disorder compared to veterans with no justice involvement. Pharmacotherapy rates are low overall, suggesting that more work can be done to connect veterans to these medications.

A Pilot Study of the Safety and Initial Efficacy of Ivermectin for the Treatment of Alcohol Use Disorder.

Ivermectin (IVM) is an antiparasitic agent that has been shown to reduce alcohol intake in mice, suggesting IVM as a potential treatment for alcohol use disorder (AUD). However, the safety profile of IVM administered in combination with an intoxicating dose of alcohol has not been characterized in humans. This pilot project sought to provide the first clinical evidence that IVM could be repositioned as an AUD pharmacotherapy by examining (i) the safety of combining IVM (30mg oral , once a day [QD]) with an intoxicating dose of intravenous alcohol (0.08g/dl) and (ii) the effects of IVM on alcohol cue-induced craving and subjective response to alcohol. Eleven individuals with AUD participated in a randomized, placebo-controlled, crossover study in which they received the study medication, participated in a cue exposure paradigm followed by intravenous alcohol administration, and remained in an inpatient unit overnight for observation. IVM treatment, versus placebo, did not increase the number or severity of adverse effects during alcohol administration or throughout the visit. However, IVM did not reduce cue-induced craving nor did it significantly affect subjective response to alcohol. These results suggest that IVM (30mg oral, QD) is safe in combination with an intoxicating dose of alcohol, but do not provide evidence that this dose of IVM is effective in reducing alcohol craving or its reinforcing effects. Given the preclinical data suggesting IVM is effective in reducing alcohol consumption in mice, additional studies testing larger samples and alternate dosing regimens are warranted to further characterize the potential efficacy of IVM as an AUD treatment.

The Effect of Varenicline on the Neural Processing of Fearful Faces and the Subjective Effects of Alcohol in Heavy Drinkers.

Pharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an α4β2-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored. In this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2mg/d) or placebo. After 2weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined. Results indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol. Our results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.

The Reasons for Heavy Drinking Questionnaire: Factor Structure and Validity in Alcohol-Dependent Adults Involved in Clinical Trials.

People consume alcohol at problematic levels for many reasons. These different motivational pathways may have different biological underpinnings. Valid, brief measures that discriminate individuals' reasons for drinking could facilitate inquiry into whether varied drinking motivations account for differential response to pharmacotherapies for alcohol use disorders. The current study evaluated the factor structure and predictive validity of a brief measure of alcohol use motivations developed for use in randomized clinical trials, the Reasons for Heavy Drinking Questionnaire (RHDQ). The RHDQ was administered before treatment to 265 participants (70% male) with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, in three pharmacotherapy randomized clinical trials. Principal components analysis was used in half the sample to determine the RHDQ factor structure. This structure was verified with confirmatory factor analysis in the second half of the sample. The factors derived from this analysis were evaluated with respect to alcohol dependence severity indices. A two-factor solution was identified. Factors were interpreted as Reinforcement and Normalizing. Reinforcement scores were weakly to moderately associated with severity, whereas normalizing scores were moderately to strongly associated with severity. In all cases in which significant associations between RHDQ scores and severity indices were observed, the relationship was significantly stronger for normalizing than for reinforcing. The RHDQ is a promising brief assessment of motivations for heavy alcohol use, particularly in the context of randomized clinical trials. Additional research should address factor structure stability in non-treatment-seeking individuals and the RHDQ's utility in detecting and accounting for changes in drinking behavior, including in response to intervention.

Service delivery and pharmacotherapy for alcohol use disorder in the era of health reform: Data from a national sample of treatment organizations

ABSTRACTBackground: Although there is a growing literature examining organizational characteristics and medication adoption, little is known about service delivery differences between specialty treatment organizations that have and have not adopted pharmacotherapy for alcohol use disorder (AUD). This study compares adopters and nonadopters across a range of treatment services, including levels of care, availability of tailored services for specific populations, treatment philosophy and counseling orientations, and adoption of comprehensive wraparound services. Methods: In-person interviews were conducted with program leaders from a national sample of 372 organizations that deliver AUD treatment services in the United States. Results: About 23.6% of organizations had adopted at least 1 AUD medication. Organizations offering pharmacotherapy were similar to nonadopters across many measures of levels of care, tailored services, treatment philosophy, and social services. The primary area of difference between the 2 groups was for services related to health problems other than AUD. Pharmacotherapy adopters were more likely to offer primary medical care, medications for smoking cessation, and services to address co-occurring psychiatric conditions. Conclusions: Service delivery differences were modest between adopters and nonadopters of AUD pharmacotherapy, with the exception of health-related services. However, the greater adoption of health-related services by organizations offering AUD pharmacotherapy represents greater medicalization of treatment, which may mean these programs are more strongly positioned to respond to opportunities for integration under health reform.

Role of astrocytic glutamate transporter in alcohol use disorder.

Alcohol use disorder (AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol (measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from non-neuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD.

Enhancing access to alcohol use disorder pharmacotherapy and treatment in primary care settings: ADaPT-PC.

BackgroundOnly 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation components.Methods/designThree large Veterans Health Administration (VHA) facilities are participating in the intervention. The intervention targets stakeholder groups with tailored strategies based on implementation theory and prior research identifying barriers to implementation of AUD pharmacotherapy. Local SUD providers and primary care mental health integration (PCMHI) providers are trained to serve as local implementation/clinical champions and receive external facilitation. PC providers receive access to consultation from local and national clinical champions, educational materials, and a dashboard of patients with AUD on their caseloads for case identification. Veterans with AUD diagnoses receive educational information in the mail just prior to a scheduled PC visit. Effectiveness of the intervention will be evaluated through an interrupted time series with matched controls to monitor change in facility level AUD pharmacotherapy prescribing rates. Following Stetler’s four-phase formative evaluation (FE) strategy, FE methods include (1) developmental FE (pre-implementation interviews with champions, PC providers, and Veterans), (2) implementation-focused FE (tracking attendance at facilitation meetings, academic detailing efforts by local champions, and patient dashboard utilization), (3) progress-focused FE (tracking rates of AUD pharmacotherapy prescribing and rates of referral to PCMHI and SUD specialty care), and (4) interpretive FE (post-implementation interviews with champions and PC providers). Analysis of FE data will be guided by the Consolidated Framework for Implementation Research (CFIR).DiscussionIf demonstrated to be successful, this implementation strategy will provide a replicable, feasible, and relative low-cost method for integrating AUD treatment services into PC settings, thereby increasing access to AUD treatment.