Allen Zweben

A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence

Abstract: The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals. This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene (5, 20, or 40 mg) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals. Participants concomitantly received 4 sessions of a motivational enhancement therapy (with a medication compliance component) delivered from trained counselors. Although more subjects in the active medication groups terminated the study early secondary to adverse events, the rates did not differ significantly from that of placebo. The 20-mg/d group experienced more insomnia, dizziness, and confusion, while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group. Most of these symptoms were mild and improved over time. Although all subjects had a reduction in heavy drinking days, craving, γ-glutamyl transferase, and carbohydrate-deficient transferrin concentrations over the course of the study, there was no difference between the active medication and placebo groups on these measures. The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups. This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics. However, possibly because of variation among the sites or the comparatively small sample size, there was no evidence of superior efficacy outcomes with nalmefene treatment.

Sustaining motivational interviewing: a meta-analysis of training studies

BACKGROUND AND AIMS Previous research indicates that motivational interviewing (MI) skills decline over time among participants in training workshops when post-workshop feedback and coaching are not provided. This study explored moderators of skill retention among trainees learning MI mainly for substance use disorder treatment in real-world treatment settings, including workshop enhancements and type and dose of post-workshop feedback and coaching. METHODS A meta-analysis of training studies was conducted with studies that reported MI skills using observational measures and that included trainees from real-world agency settings. Standardized change scores were calculated to indicate the magnitude of pre-post training change in MI skills; standardized change scores from post-training to 3 and 6+ months follow-up were calculated to indicate the sustainability of training gains over time. Effect sizes were aggregated using random effects models. RESULTS Twenty-one papers that reported the effects of MI training on agency staff were included in this review. Across studies, training yielded gains in MI skills (d = 0.76). Studies that did not include feedback and/or coaching reported eroding skills over a 6-month follow-up (d = -0.30), whereas post-workshop feedback/coaching sustained skills (d = 0.03). Effects of post-workshop feedback/coaching were moderated by frequency, duration and length of training. Moreover, studies reporting low levels of attrition from training protocols showed small increases in skills over the 6-month follow-up period (d = 0.12), whereas studies with high attrition showed skill erosion (d = -0.29). CONCLUSIONS On average, three to four feedback/coaching sessions over a 6-month period sustain skills among trainees for motivational interviewing, mainly for substance use disorder treatment. However, high rates of attrition from feedback/coaching contributes to post-workshop skill erosion.

Clinical and Methodological Utility of a Composite Outcome Measure for Alcohol Treatment Research

BACKGROUND How to capture different response patterns resulting from alcohol treatment has been a troublesome issue for alcohol researchers. A composite measure is one approach to capturing multiple treatment outcomes among diverse client populations. This article provides the rationale, development, and work conducted thus far on the composite outcome index and discusses the clinical utility of the measure. METHODS With the use of Project MATCH data, the composite outcome measure was examined in relation to self-reported alcohol consumption and alcohol problems and biological markers as well as in relation to other areas of functioning, such as psychiatric dysfunction and quality of life. Also, for assessing the stability of the measure, different composite outcomes statuses were assessed over time. RESULTS Individuals with better scores on composite outcome index had fewer percent days abstinent, consumed more alcohol when they drank, had a greater number of alcohol problems, and evidenced higher blood levels as measured by gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin. Individuals with poorer composite outcome statuses had poorer social and behavioral role functioning and mental and physical health-related quality of life. Findings on short- and long-term composite outcome statuses revealed that only a minority of clients (30%) sustained a remitted status (i.e., abstinent or moderate drinking without problems) over the 1-year follow-up, and fully 70% of the clients had reached a nonremitted status (i.e., heavy drinking and/or problems) on the composite measure at one or more time points during the 12-month follow-up. CONCLUSIONS The composite outcome index could be used usefully along with singular measures of consumption to obtain a more complete picture of what has occurred among clients posttreatment. Future work will involve the testing of the composite outcome index with other client populations and/or different treatments to further our understanding of the varying response patterns found among alcohol-dependent clients.

Composite Outcome Measures in Alcoholism Treatment Research: Problems and Potentialities

Alcoholism treatment researchers have increasingly incorporated multiple measures representing multiple dimensions in assessing treatment outcomes. However, no satisfactory model exists for examining the dynamic interrelationships of multiple measures in determining clinically meaningful and interpretable outcomes. One approach to analyzing multiple outcomes is to combine them into a composite measure. In their most elementary form, composite measures combine alcohol consumption and consumption-related problems dimensions into treatment outcome classifications. This paper discusses conceptual and methodological issues in studies reporting composite outcomes and provides a model and recommendations for using composite measures in alcohol treatment research.

Effective Strategies for Maintaining Research Participation in Clinical Trials

Achieving high protocol adherence is essential for ensuring the overall success and scientific merit of clinical trials. Strategies for maximizing recruitment and treatment adherence have been previously explored in the literature. There has been less focus, however, on effective methods for maintaining participants in research follow-up. This article examines factors associated with poor follow-up rates as well as strategies for facilitating research commitment and addressing sources of nonadherence. Special attention is devoted to alcohol- and substance-dependent populations, groups known to have poor adherence rates. Examples are drawn from the COMBINE Study, an NIAAA-funded, nationwide, multisite, combined behavioral and pharmacotherapy trial for alcohol problems that achieved high one-year follow-up rates. The important role of coordinating centers in facilitating research retention is also discussed.

Does Session Attendance by a Supportive Significant Other Predict Outcomes in Individual Treatment for Alcohol Use Disorders

BACKGROUND A significant amount of research has supported the efficacy of couple versus individual treatment for alcohol use disorders, yet little is known about whether involving a significant other during the course of individual treatment can improve outcomes. Likewise, several barriers to couple treatment exist and a more flexible approach to significant other involvement may be warranted. METHODS This study constituted secondary analyses of the COMBINE data, a randomized clinical trial that combined pharmacotherapy and behavioral intervention for alcohol dependence. Data were drawn from the 16-week individual combined behavioral intervention (CBI), which had 776 participants, 31% of which were female, and 23% were non-white. The current study examined whether attendance by a supportive significant other (SSO) during CBI sessions would predict better outcomes. It was further hypothesized that active SSO involvement, defined by attendance during drink refusal or communication skills training sessions, would predict better outcomes. RESULTS SSOs attended at least 1 session for 26.9% of clients. Clients with SSOs who attended at least 1 session had significantly fewer drinking days and fewer drinking-related problems at the end of treatment. The presence of an SSO during a drink refusal training session predicted significantly better outcomes, as compared to SSO attendance at other sessions and drink refusal training without an SSO present. SSO attendance at a communication training session did not predict better outcomes. CONCLUSIONS These results suggest that specific types of active involvement may be important for SSO-involved treatment to have greater efficacy than individual treatment.

Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial

Importance Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking. Objectives To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence. Design, Setting, and Participants This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017. Interventions Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking. Main Outcomes and Measures Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16. Results Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, −0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, −0.69; 95% CI, −1.63 to 0.25; P = .15; Cohen d = −0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = −0.60; 95% CI, −1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07). Conclusions and Relevance Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks. Trial Registration clinicaltrials.gov Identifier: NCT01553136

Assessment and Treatment Implications of Adjustment and Coping Capacities in Children Living with Alcoholic Parents

A developmental framework is offered for assessing and designing interventions for children living with alcoholic parents. The assessment scheme is comprised of several components: aspects related to the stressor events (parental alcoholism), characteristics of the individual child, and qualities of the childs social environment. The assessment and intervention procedures which are discussed attend to a complex set of factors that serve mediating, potentiating, and protective functions for children. The proposed framework is based upon contemporary models of development and research concerning adjustment and coping among children. This framework is offered as a foundation to be utilized in the planning and implementation of appropriate and suitable interventions for these children.

The clinical utility of the Medication Adherence Questionnaire (MAQ) in an alcohol pharmacotherapy trial

BACKGROUND Medication nonadherence is a ubiquitous problem in pharmacology treatment for alcohol use disorders. Unintentional and purposeful nonadherence as measured by the Medication Adherence Questionnaire (MAQ) has been shown to predict problems with medication adherence; however, feedback from the MAQ has never been incorporated into a behavioral intervention to facilitate medication adherence. We assessed the integration of the MAQ into medical management (MM), a counseling approach frequently employed in conjunction with alcohol pharmacotherapy, to determine whether prior patterns of nonadherence could be addressed effectively to promote medication adherence. METHODS We conducted a post-hoc analysis of data from 131 alcohol dependent smokers who participated in a double blind, placebo controlled study of varenicline for the treatment of alcohol dependence. At baseline, participants completed a single administration of the MAQ, which asks 2 questions about unintentional nonadherence (e.g., forgetting) and 2 questions about purposeful nonadherence (e.g., stopping because feeling good or feeling bad). Based on these responses, participants were divided into 1 of 3 three categories. Adherent (n=60), Unintentional or Purposeful Nonadherent (n=50) and Unintentional and Purposeful Nonadherent (n=21). Over the course of the 16-week treatment period, patients were expected to participate in 12 medical management (MM) sessions; a brief psychosocial treatment. Feedback based on the MAQ responses was integrated into the MM sessions to facilitate medication and treatment adherence. RESULTS The 3 adherence groups were compared on baseline characteristics, medication adherence, treatment attendance and end-of-treatment patient ratings of treatment helpfulness. Baseline demographics and characteristics were not significantly different among the three categories. We found no statistically significant differences among the three groups with respect to pill adherence, treatment attendance, and treatment satisfaction ratings. CONCLUSIONS The findings suggest that the incorporation of MAQ feedback into the MM approach could be effective in mitigating risks associated with prior patterns of nonadherence suggesting that further testing of the integrated behavioral approach is warranted.

Commentary on the Adding Individual Psychotherapy After Relapse in a Pharmacotherapy Trial: Commentary on the PREDICT Study

BACKGROUND With few exceptions there has been a dearth of research evaluating the independent and combined effects of a promising medication and an effective behavioral intervention for alcohol problems. Few studies have incorporated both theory and empirical findings to ascertain how the combination of medication and behavioral intervention interact or work synergistically to produce better outcomes or why a particular combination of pharmacological and behavioral treatment works better than another combination or either of the interventions employed alone. METHODS The PREDICT Study is one of the few pharmacotherapy trials that has utilized a behavioral intervention to reduce/delay relapse to heavy drinking. The findings in the PREDICT Study were reviewed to gain a better understanding of how the combination of pharmacotherapy and behavioral intervention can be employed to manage the course of recovery for individuals with alcohol use disorders (AUDs). RESULTS Findings in the PREDICT Study show that behavioral interventions and pharmacotherapies have complementary functions that can be utilized to address the differential needs, capabilities, and resources associated with AUDs. However, researchers were forced to rely mainly on their own clinical experiences rather than an overarching conceptual model in determining how the approach should be employed with AUD patients, thereby limiting the conclusions that could be drawn from the study findings. CONCLUSIONS Different vulnerabilities underlying AUDs should be considered in determining what kinds of behavioral interventions should be paired with particular medications. At the same time, we need to have a better understanding of the clinical course of pharmacobehavioral treatment to deal with the array of problems/situations that arise over the course of combination therapy.