Medications For Alcohol Use Disorder Research Articles

Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder

Current medications for alcohol use disorder do not target brain noradrenergic pathways. Theoretical and preclinical evidence suggests that noradrenergic circuits may be involved in alcohol reinforcement and relapse. After a positive pilot study, the authors tested the α-1 adrenergic receptor antagonist prazosin to treat alcohol use disorder in a larger sample. Ninety-two participants with alcohol use disorder but without posttraumatic stress disorder were randomly assigned to receive prazosin or placebo in a 12-week double-blind study. Medication was titrated to a target dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime by the end of week 2. The behavioral platform was medical management. Participants provided daily data on alcohol consumption. Generalized linear mixed-effects models were used to examine the impact of prazosin compared with placebo on number of drinks per week, number of drinking days per week, and number of heavy drinking days per week. Eighty participants completed the titration period and were included in the primary analyses. There was a significant interaction between condition and week for both number of drinks and number of heavy drinking days, such that the rate of drinking and the probability of heavy drinking showed a greater decrease over time for participants in the prazosin condition compared with those in the placebo condition. Participants in the prazosin condition were more likely to report drowsiness and edema than participants in the placebo condition. Prazosin holds promise as a harm-reduction pharmacologic treatment for alcohol use disorder and deserves further evaluation by independent research groups.

Medications for Alcohol Use Disorder and Predicting Severe Withdrawal

Medications for Alcohol Use Disorder and Predicting Severe Withdrawal

Mobile alcohol biosensors and pharmacotherapy development research.

Recent advances in biosensor technology herald a major shift in the way alcohol use will be tracked in humans. Wearable biosensors can passively and continuously monitor wearers' alcohol consumption in real time. An important application of these biosensors is to improve the way medication for alcohol use disorder (AUD) is tested in clinical research. Both laboratory-based screening paradigms and clinical trials have methodological problems that impact their efficiency and predictive validity. Medication screening using laboratory-based methods is a resource-intensive assessment of a single episode of behavior in a non-representative setting. Clinical trials rely on participant self-report to document medication-induced changes in drinking behavior. This review describes how mobile biosensors can be leveraged to improve AUD medication development research. We first review the current state of alcohol biosensor technology with a focus on strengths and limitations of the devices. We describe how multiple biosensors can be combined to create a far more detailed record of drinking compared to single biosensor platforms. We then discuss each phase of the medication development pipeline in turn (i.e., phases 1-4) and describe how mobile biosensors can be incorporated in standard medication testing paradigms to improve efficiency and predictive validity. We conclude with discussion of challenges associated with using currently available biosensors for medication testing and recommendations for researchers wishing to incorporate alcohol biosensors into their own research.

Cyclic nucleotide phosphodiesterases: potential therapeutic targets for alcohol use disorder.

Alcohol use disorder (AUD), which combines the criteria of both alcohol abuse and dependence, contributes as an important causal factor to multiple health and social problems. Given the limitation of current treatments, novel medications for AUD are needed to better control alcohol consumption and maintain abstinence. It has been well established that the intracellular signal transduction mediated by the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) crucially underlies the genetic predisposition, rewarding properties, relapsing features, and systemic toxicity of compulsive alcohol consumption. On this basis, the upstream modulators phosphodiesterases (PDEs), which critically control intracellular levels of cyclic nucleotides by catalyzing their degradation, are proposed to play a role in modulating alcohol abuse and dependent process. Here, we highlight existing evidence that correlates cAMP and cGMP signal cascades with the regulation of alcohol-drinking behavior and discuss the possibility that PDEs may become a novel class of therapeutic targets for AUD.

Alcohol-Related Nurse Care Management in Primary Care

Experts recommend that alcohol use disorders (AUDs) be managed in primary care, but effective approaches are unclear. To test whether 12 months of alcohol care management, compared with usual care, improved drinking outcomes among patients with or at high risk for AUDs. This randomized clinical trial was conducted at 3 Veterans Affairs (VA) primary care clinics. Between October 11, 2011, and September 30, 2014, the study enrolled 304 outpatients who reported heavy drinking (≥4 drinks per day for women and ≥5 drinks per day for men). Nurse care managers offered outreach and engagement, repeated brief counseling using motivational interviewing and shared decision making about treatment options, and nurse practitioner-prescribed AUD medications (if desired), supported by an interdisciplinary team (CHOICE intervention). The comparison was usual primary care. Primary outcomes, assessed by blinded telephone interviewers at 12 months, were percentage of heavy drinking days in the prior 28 days measured by timeline follow-back interviews and a binary good drinking outcome, defined as abstinence or drinking below recommended limits in the prior 28 days (according to timeline follow-back interviews) and no alcohol-related symptoms in the past 3 months as measured by the Short Inventory of Problems. Of 304 participants, 275 (90%) were male, 206 (68%) were white, and the mean (SD) age was 51.4 (13.8) years. At baseline, both the CHOICE intervention (n = 150) and usual care (n = 154) groups reported heavy drinking on 61% of days (95% CI, 56%-66%). During the 12-month intervention, 137 of 150 patients in the intervention group (91%) had at least 1 nurse visit, and 77 of 150 (51%) had at least 6 nurse visits. A greater proportion of patients in the intervention group than in the usual care group received alcohol-related care: 42% (95% CI, 35%-49%; 63 of 150 patients) vs 26% (95% CI, 19%-35%; 40 of 154 patients). Alcohol-related care included more AUD medication use: 32% (95% CI, 26%-39%; 48 of 150 patients in the intervention group) vs 8% (95% CI, 5%-13%; 13 of 154 patients in the usual care group). No significant differences in primary outcomes were observed at 12 months between patients in both groups. The percentages of heavy drinking days were 39% (95% CI, 32%-47%) and 35% (95% CI, 28%-42%), and the percentages of patients with a good drinking outcome were 15% (95% CI, 9%-22%; 18 of 124 patients) and 20% (95 % CI, 14%-28%; 27 of 134 patients), in the intervention and usual care groups, respectively (P = .32-.44). Findings at 3 months were similar. The CHOICE intervention did not decrease heavy drinking or related problems despite increased engagement in alcohol-related care. clinicaltrials.gov Identifier: NCT01400581.

APA Releases Practice Guideline for AUD Pharmacotherapy

Back to table of contents Previous article Next article PsychopharmacologyFull AccessAPA Releases Practice Guideline for AUD PharmacotherapyNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:19 Jan 2018https://doi.org/10.1176/appi.pn.2018.pp1b4AbstractAPA’s new guideline for alcohol use disorder provides information on the comparative benefits and risks of acamprosate, disulfiram, gabapentin, naltrexone, and topiramate. Despite the high prevalence of alcohol use disorder (AUD) in the United States, and the significant financial and public health burden of excess drinking, most people do not receive adequate treatment for this disorder. A recent analysis estimated that only 1 in 10 people diagnosed with AUD receive any treatment, and fewer still receive an evidence-based treatment. There are likely many reasons for the underuse of treatments for AUD, including a lack of awareness by both patients and providers about their options. To increase awareness about medications available to treat AUD, APA earlier this month released the Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder.“This new guideline is an important step in bringing effective, evidence-based treatments for alcohol use disorder to many more people and in helping address the public health burden of alcohol use,” APA President Anita Everett, M.D., said in a press release announcing the guideline’s release.This guideline offers recommendations or suggestions on various aspects of AUD pharmacotherapy. Recommendations reflect confidence that the benefits of the intervention clearly outweigh the harms. Suggestions reflect more uncertainty; the benefits of the intervention are still viewed as outweighing the harms, but the balance between the two may be harder to judge and patient preference is likely to play a greater role in deciding the treatment used.The specific guidance statements related to the prescribing of the five AUD medications are as follows: APA recommends that naltrexone or acamprosate be offered to patients with moderate to severe AUD who want to reduce drinking or achieve abstinence, prefer pharmacotherapy or have not responded to nonpharmacological treatments alone, and have no contraindications to the use of these medications.APA recommends that acamprosate not be used by patients who have severe renal impairment. For individuals with mild to moderate renal impairment, APA recommends that acamprosate not be used as a first-line treatment and, if used, the dose of acamprosate be reduced compared with recommended doses in individuals with normal renal function.APA recommends that naltrexone not be used by patients who have acute hepatitis or hepatic failure.APA recommends that naltrexone not be used as a treatment for AUD by individuals who use opioids or who have an anticipated need for opioids.APA suggests that disulfiram be offered to patients with moderate to severe AUD who want to achieve abstinence and prefer disulfiram or are intolerant to or have not responded to naltrexone and acamprosate. Patients should be informed of the risks of alcohol consumption while taking disulfiram (adverse reactions such as flushing and elevated heart rate occur if alcohol is consumed within 12 to 24 hours of taking disulfiram), and have no contraindications to the use of this medication.APA suggests that topiramate or gabapentin be offered to patients with moderate to severe AUD who want to reduce drinking or achieve abstinence and prefer topiramate or gabapentin or are intolerant to or have not responded to naltrexone and acamprosate, and have no contraindications to the use of these medications.In addition, the practice guideline includes recommendations and suggestions related to the psychiatric evaluation of patients with AUD and treatment planning, which are integral first steps toward using pharmacotherapy to treat AUD. While the guideline statements provide a good synopsis of the current understanding of these medications, Oscar Bukstein, M.D., M.P.H., a member of the Guideline Writing Group, said that it is important for physicians to read other portions of the practice guideline, which include explanations for each recommendation and suggestion.“The explanations provide important context about when and where certain pharmacotherapies might be appropriate,” said Bukstein, who is a psychiatrist at Boston Children’s Hospital. Bukstein added patient preference is always important to consider when choosing a pharmacotherapy. He explained that this is why the language reflected some interchangeability among the available options as opposed to ranking the medications in an algorithmic fashion. Still, as noted in the guideline, naltrexone and acamprosate are the treatments best supported by clinical and research evidence. “It’s important to keep in mind that these medications are to be used as adjuncts in a comprehensive AUD treatment program, which is why it was important to include statements related to treatment planning,” Bukstein told Psychiatric News. Recommending a particular nonpharmacological approach to be used alongside pharmacotherapy was outside the scope of this practice guideline. ■ ISSUES NewArchived

The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder.

The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder.

Medications for alcohol use disorders: An overview.

Patients who suffer from alcohol use disorders (AUDs) usually go through various socio-behavioral and pathophysiological changes that take place in the brain and other organs. Recently, consumption of unhealthy food and excess alcohol along with a sedentary lifestyle has become a norm in both developed and developing countries. Despite the beneficial effects of moderate alcohol consumption, chronic and/or excessive alcohol intake is reported to negatively affect the brain, liver and other organs, resulting in cell death, organ damage/failure and death. The most effective therapy for alcoholism and alcohol related comorbidities is alcohol abstinence, however, chronic alcoholic patients cannot stop drinking alcohol. Therefore, targeted therapies are urgently needed to treat such populations. Patients who suffer from alcoholism and/or alcohol abuse experience harmful effects and changes that occur in the brain and other organs. Upon stopping alcohol consumption, alcoholic patients experience acute withdrawal symptoms followed by a protracted abstinence syndrome resulting in the risk of relapse to heavy drinking. For the past few decades, several drugs have been available for the treatment of AUDs. These drugs include medications to reduce or stop severe alcohol withdrawal symptoms during alcohol detoxification as well as recovery medications to reduce alcohol craving and support abstinence. However, there is no drug that completely antagonizes the adverse effects of excessive amounts of alcohol. This review summarizes the drugs which are available and approved by the FDA and their mechanisms of action as well as the medications that are under various phases of preclinical and clinical trials. In addition, the repurposing of the FDA approved drugs, such as anticonvulsants, antipsychotics, antidepressants and other medications, to prevent alcoholism and treat AUDs and their potential target mechanisms are summarized.

Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals.

Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg-1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97±10.65, P=0.04, Cohen's d=0.74). Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin, compared to placebo (P=0.03). The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration. Neuroimaging data showed that ghrelin increased the alcohol-related signal in the amygdala (P=0.01) and modulated the food-related signal in the medial orbitofrontal cortex (P=0.01) and nucleus accumbens (P=0.08). These data indicate that ghrelin signaling affects alcohol seeking in humans and should be further investigated as a promising target for developing novel medications for alcohol use disorder.

Barriers to and Facilitators of Alcohol Use Disorder Pharmacotherapy in Primary Care: A Qualitative Study in Five VA Clinics.

Three medications are FDA-approved and recommended for treating alcohol use disorders (AUD) but they are not offered to most patients with AUD. Primary care (PC) may be an optimal setting in which to offer and prescribe AUD medications, but multiple barriers are likely. This qualitative study used social marketing theory, a behavior change approach that employs business marketing techniques including "segmenting the market," to describe (1) barriers and facilitators to prescribing AUD medications in PC, and (2) beliefs of PC providers after they were segmented into groups more and less willing to prescribe AUD medications. Qualitative, interview-based study. Twenty-four providers from five VA PC clinics. Providers completed in-person semi-structured interviews, which were recorded, transcribed, and analyzed using social marketing theory and thematic analysis. Providers were divided into two groups based on consensus review. Barriers included lack of knowledge and experience, beliefs that medications cannot replace specialty addiction treatment, and alcohol-related stigma. Facilitators included training, support for prescribing, and behavioral staff to support follow-up. Providers more willing to prescribe viewed prescribing for AUD as part of their role as a PC provider, framed medications as a potentially effective "tool" or "foot in the door" for treating AUD, and believed that providing AUD medications in PC might catalyze change while reducing stigma and addressing other barriers to specialty treatment. Those less willing believed that medications could not effectively treat AUD, and that treating AUD was the role of specialty addiction treatment providers, not PC providers, and would require time and expertise they do not have. We identified barriers to and facilitators of prescribing AUD medications in PC, which, if addressed and/or capitalized on, may increase provision of AUD medications. Providers more willing to prescribe may be the optimal target of a customized implementation intervention to promote changes in prescribing.

Effects of a multifaceted implementation intervention to increase utilization of pharmacological treatments for alcohol use disorders in the US Veterans Health Administration

Over 16 million Americans meet diagnostic criteria for alcohol use disorder (AUD), but only 7.8% of them receive formal treatment each year. Safe and effective pharmacological treatments for AUD exist; however, they are rarely prescribed. Therefore, we developed and pilot tested a multifaceted implementation intervention to improve consideration and receipt of effective pharmacologic treatments for AUD, focusing on primary care settings where patients have the most frequent contact with healthcare systems. The intervention included training of local providers to serve as champions and a website for primary care providers that included educational materials, a case-finding dashboard, and contact information for local and national clinical experts. We also mailed patients educational material about treatment options. The intervention was implemented at three large facilities of the Veterans Health Administration (VHA). An interrupted time series design, analyzed with segmented logistic regression, was used to evaluate the intervention's effects. The odds of a patient with AUD receiving one of the AUD medications was increasing throughout the pre-implementation period, and the rate of change (slope) increased significantly in the implementation period. Translating these numbers into percentages, at baseline 2.9% of patients filled a prescription for an AUD medication within 30days of a primary care visit. This increased to 3.8% by the end of the pre-implementation period (increasing 0.037% per month), and increased to 5.2% by the end of the implementation period (increasing 0.142% per month). However, the intervention effect was not significant when control sites were added, suggesting that improvement may have been driven by secular trends rather than solely by this intervention. Although the intervention was feasible, it was not effective. Continued analysis of process and implementation data including qualitative interviews with key stakeholders, may elucidate the reasons this intervention was not successful and ways to strengthen its effects.

Promoting Adoption of Medication for Opioid and Alcohol Use Disorders Through System Change.

The Medication Research Partnership (MRP), a collaboration between a national commercial health plan and nine addiction treatment centers, implemented organizational and system changes to promote use of federally approved medications for treatment of alcohol and opioid use disorders. A difference-in-differences analysis examined change over time in the percentage of patients receiving a prescription medication for alcohol or opioid use disorders treated in MRP (n = 9) and comparison (n = 15) sites. MRP clinics experienced a 2.4-fold increase in patients receiving an alcohol or opioid prescription (13.2% at baseline to 31.7% at 3 years after MRP initiation); comparison clinics experienced significantly less change (17.6% to 23.5%) with an adjusted difference-in-differences of 12.5% (95% CI [5.4, 19.6], p = .001). MRP sites increased the patients with prescriptions to treat opioid use disorder from 17.0% (baseline) to 36.8% (3 years after initiation), with smaller changes observed in comparison sites (23.2% to 24.0%) and a 3-year post-initiation adjusted difference-in-differences of 19% (95% CI [8.5, 29.5], p = .000). Medications for alcohol use disorders increased in both MRP (9.0% to 26.5%) and comparison sites (11.4% to 23.1%). Promoting the use of medications to support recovery required complex interventions. The Advancing Recovery System Change Model, initially developed in publicly funded systems of care, was successfully adapted for commercial sector use. The model provides a framework for providers and commercial health plans to collaborate and increase patient access to medications.

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.

NIAAA Strategic Plan Targets Areas Where Immediate Impact Is Possible

Back to table of contents Previous article Next article Government NewsFull AccessNIAAA Strategic Plan Targets Areas Where Immediate Impact Is PossibleNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:12 Jun 2017https://doi.org/10.1176/appi.pn.2017.6b6AbstractNIAAA’s five-year plan will emphasize areas where most progress can be made in the coming years and includes developing new tools and paradigms for diagnosing alcohol-related disorders.The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has released a five-year strategic plan that focuses on areas in which the institute hopes to advance the diagnosis, treatment, and prevention of alcohol-related problems. The plan encompasses five broad goals for biomedical research: identifying the mechanisms underlying alcohol’s effects, improving diagnosis of alcohol disorders and their consequences, developing and improving prevention strategies, advancing treatment options, and increasing public awareness.“Rather than just create a list of generic strategies within each goal, NIAAA focused on key areas where we are poised to make the most progress in the coming years,” said NIAAA Acting Deputy Director Patricia Powell, Ph.D.Powell added that this new vision will not dramatically shift funding allocated to NIAAA’s various research portfolios. Rather, each specific portfolio will prioritize certain objectives. For example, under the diagnosis goal, NIAAA is investing in three-dimensional image analysis to improve the diagnosis of fetal alcohol spectrum disorder (FASD). These scanners create heat maps of facial topography that can be quickly analyzed to determine whether an FASD is present. The institute also hopes to identify prenatal biomarkers, whether metabolic, genetic, or image based, to diagnose FASD in utero and allow for early intervention efforts.Pharmacology is another important area. There are only three FDA-approved medications for alcohol use disorder (AUD), and each has some drawbacks. Powell said that recent early-stage clinical work in this area has shown some promise (for example, a vasopressin receptor antagonist, ABT-436, has had encouraging phase 2b clinical results), but agreed that many obstacles remain that slow the drug-development process and contribute to high failure rates of initially promising drugs.As part of the strategic plan, NIAAA is seeking to improve both animal models of alcohol disorders and human laboratory paradigms. “We must appreciate that alcohol disorders are heterogenous and build clinical studies around specific aspects of the disorder,” she said. For example, if a medication being studied is targeted at anxiety pathways, the research needs to include participants with high anxiety levels and employ validated tests that assess anxiety-induced cravings.Powell said that NIAAA will also continue to develop better technology for measuring alcohol exposure. Current tools for alcohol monitoring work well but can be cumbersome and do not offer true real-time monitoring. The institute recently held a monitoring-device competition that resulted in a prototype wristband that continuously measures alcohol levels via sweat readings. Such a device is useful for not only research purposes but also commercial applications so that, for example, individuals can unobtrusively monitor their level of intoxication, said Powell.Perhaps one of the most significant items noted in the NIAAA strategic plan is the proposed development of a new diagnostic model of AUD, the Addictions Neuroclinical Assessment (ANA). The ANA is envisioned as a wide-ranging battery of tests, including genetic, neuroimaging, and behavioral assessments, that can identify clinical subtypes of AUD, which in turn can guide the development of personalized treatments.In some ways, this initiative resembles the National Institute of Mental Health’s (NIMH) initiative to reclassify mental disorders by integrating clinical symptoms with neurobiological measures.“Our approach is not as sweeping as NIMH’s, since we are only looking at one psychiatric disorder, but it goes back to the fact that AUD is heterogenous,” Powell said. “One person may drink too much because alcohol is wonderful and intoxicating, while another does so because that person can’t leave the house and face the world. Right now, both would be considered as having the same disease.”Even though the approach may not be that sweeping, Powell said this is still a dramatic change, and NIAAA will pilot the adoption of ANA within the institute’s intramural research division. ■The NIAAA Strategic Plan 2017-2021: Charting a Course for the Next Five Years of Alcohol Research can be accessed here. ISSUES NewArchived

Patient-centered primary care for adults at high risk for AUDs: the Choosing Healthier Drinking Options In primary CarE (CHOICE) trial

BackgroundMost patients with alcohol use disorders (AUDs) never receive alcohol treatment, and experts have recommended management of AUDs in primary care. The Choosing Healthier Drinking Options In primary CarE (CHOICE) trial was a randomized controlled effectiveness trial of a novel intervention for primary care patients at high risk for AUDs. This report describes the conceptual and scientific foundation of the CHOICE model of care, critical elements of the CHOICE trial design consistent with the Template for Intervention Description and Replication (TIDieR), results of recruitment, and baseline characteristics of the enrolled sample.MethodsThe CHOICE intervention is a multi-contact, extended counseling intervention, based on the Chronic Care Model, shared decision-making, motivational interviewing, and evidence-based options for managing AUDs, designed to be practical in primary care. Outpatients who received care at 3 Veterans Affairs primary care sites in the Pacific Northwest and reported frequent heavy drinking (≥4 drinks/day for women; ≥5 for men) were recruited (2011–2014) into a trial in which half of the participants would be offered additional alcohol-related care from a nurse. CHOICE nurses offered 12 months of patient-centered care, including proactive outreach and engagement, repeated brief motivational interventions, monitoring with and without alcohol biomarkers, medications for AUDs, and/or specialty alcohol treatment as appropriate and per patient preference. A CHOICE nurse practitioner was available to prescribe medications for AUDs.ResultsA total of 304 patients consented to participate in the CHOICE trial. Among consenting participants, 90% were men, the mean age was 51 (range 22–75), and most met DSM-IV criteria for alcohol abuse (14%) or dependence (59%). Many participants also screened positive for tobacco use (44%), depression (45%), anxiety disorders (30-41%) and non-tobacco drug use disorders (19%). At baseline, participants had a median AUDIT score of 18 [Interquartile range (IQR) 14–24] and a median readiness to change drinking score of 5 (IQR 2.75–6.25) on a 1–10 Likert scale.ConclusionThe CHOICE trial tested a patient-centered intervention for AUDs and recruited primary care patients at high risk for AUDs, with a spectrum of severity, co-morbidity, and readiness to change drinking.Trial registration The trial is registered at clinicaltrial.gov (NCT01400581).

Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study

Recently, the Food and Drug Administration (FDA) proposed to expand the options for primary end points in the development of medications for alcohol use disorder to include either abstinence from alcohol or a nonabstinent outcome: no heavy drinking days (with a heavy drinking day defined as more than 3 drinks per day for women and more than 4 drinks per day for men [>3/>4 cutoff]). The FDA also suggested that 6months would be the most appropriate length for a clinical trial to demonstrate the stability of this nonabstinent drinking outcome. However, few alcohol clinical trials have examined the stability of nonheavy drinking during and after treatment. In a secondary analysis of the COMBINE study data (n=1,383), we examined transitions in heavy drinking days during the course of treatment (months 1 through 4), during the transition out of treatment (months 4 through 7), and up to 12months afterward (months 13 through 16) using latent variable mixture models. Heavy drinking and nonheavy drinking were relatively stable in consecutive months (minimum agreement [kappa]=0.64 for months 1 to 2). Most individuals were stable low-risk drinkers/abstainers or heavy drinkers by the end of treatment, as characterized by a 10% probability (or less) of transitioning out of either a no heavy drinking state or a heavy drinking state. More than two-thirds of the heavy drinkers who exceeded the heavy drinking threshold during treatment reported, on average, a 64% reduction in drinking frequency and a 38% reduction in drinking intensity from pretreatment drinking levels. The results show stability of no heavy drinking as an outcome within the first 4months of treatment and that the >3/>4 drink cutoff may mask substantial reductions in alcohol consumption among some patients. Future studies should explore the clinical utility of reduction end points.

The safety and efficacy of baclofen to reduce alcohol use in veterans with chronic hepatitis C: a randomized controlled trial.

Alcohol use disorders (AUDs) are common among people with chronic hepatitis C (HCV) and accelerate the development of fibrosis and cirrhosis caused by HCV. Baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist, differs from medications for AUDs currently approved by the United States Food and Drug Administration (FDA), as it is metabolized primarily through the kidneys. The primary outcome of this study was to compare baclofen with a placebo in the percentage of days abstinent from alcohol. A double-blind, placebo-controlled randomized trial. Hepatology clinics in four separate US Veteran Affairs Medical Centers in the United States. One hundred and eighty Veteran men and women older than 18years with chronic HCV, a comorbid AUD and current alcohol use. Oral baclofen was given at dosages of 0 (placebo) or 30mg/day over 12weeks with concomitant manual-guided counseling. The primary measurement was percentage of days abstinent during the 12-week study period between the baclofen and placebo groups [measured by time-line follow-back (TLFB)]. Secondary measurements were the percentage of Veterans who achieved complete abstinence, the percentage of Veterans who achieved no heavy drinking between weeks 4 and 12 of the study, alcohol craving, anxiety, depression and post-traumatic stress disorder (PTSD). Primary outcome: compared with placebo, baclofen did not improve the percentage of days abstinent. For all subjects there were significant reductions from baseline to 12weeks in percentage of days abstinent from 37.0% [standard error (SE)=2.7] to 68.6% (SE=2.8, F(1151.1) =66.1, P<0.001). However, there was no statistically significant difference between groups for change in percentage of days abstinent over the 12-week study period [absolute difference 1.3% (-9.1 to 1.7%), F(1152.6) =0.005, P=0.95]. Of subjects who completed the first 4weeks of the study, 8.9% (15 of 168) achieved complete abstinence; 10.1% (nine of 89) in the placebo group and 7.6% (six of 79) in the baclofen group [χ2(1) =0.33, odds ratio (OR)=0.73 (0.24-2.15)]. The percentage of no heavy drinking for all subjects between weeks 4 and 12 was 20.2% (34 of 168), but no statistically significant differences were found between placebo 15.7% (14 of 89) and baclofen 25.3% (20 of 79) [χ2(1) =2.38, OR=1.82 (0.85-3.90)]. There were significant reductions for all subjects in all other secondary variables over the course of the study, but no differences between groups. Measures of various biomarkers of alcohol use did not change significantly throughout the course of the study for either the baclofen or placebo groups. Baclofen administered at 30mg/day does not appear to be superior to placebo in increasing abstinence or in reducing alcohol use, cravings for alcohol or anxiety among people with alcohol use disorder.

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.

Risk/Benefit Discussion of Alcohol Use Disorder Medications: Behavioral Economic Considerations and General Recommendations

Background: Despite the development of several relatively safe and effective medications to treat alcohol use disorder (AUD), underutilization of these medications continues to be a challenge. With other factors, judgments about medications’ risks and benefits can influence prescribers’ practices and patients’ acceptance of these medications. Objective: Describe how behavioral economic principles and presentation of risks/benefits of AUD medications can impact these medications’ utilization and suggest guidelines for how prescribers should describe these medications to patients. Methods: Literature selected by the authors was used in this commentary and formulation of guidelines. Results: Behavioral economic principles relevant to judging risks and benefits of AUD medications include salience, recency, the halo effect, narrative thinking, avoiding cognitive dissonance, and patients’ interoceptive effects. Benefits of reduced alcohol use may be too abstract without elaboration. Medications are more likely to be taken by patients who envision their benefits as salient, prompt, and consistent with other ideas they have about their alcohol use and/or tailored to their psychological state. Explaining risks and benefits using established quantitative and qualitative terms has predictable effects on patients’ perceptions. Risk/benefit discussion should be bi-directional between patient and provider, personalized to issues valued by each patient, and tailored to the individual’s alcoholinduced state. We propose methods to improve information transfer and reduce biased decision making. Conclusion: Whether and how a risk/benefit discussion of AUD medications is conducted can influence utilization of these medications.

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).