A Descriptive Review and Meta-Regression Study of Demographic and Study Context Factors in US Clinical Trials of Cognitive Behavioral Interventions for Alcohol or Other Drug Use.

Objectives. Cognitive-Behaviorally Based Interventions (CBIs) are evidence-based treatments for alcohol and other drug (AOD) use with potential variable effectiveness by population sub-groups. This study used evidence synthesis to examine treatment effect by demographic and study context factors in clinical trials of CBI for AOD. Methods. Studies were systematically identified, and their characteristics and outcome data were extracted and summarized. Standardized mean differences were calculated for within- and between-condition effects on substance use outcomes. Demographic and study context moderators were identified during data acquisition and several sensitivity analyses were conducted. Results. The sample included K = 29 trials and a total of 15 study-level moderators were examined. Information on participants' age, biological sex, and race were reported in at least 26 trials, but information on gender identity, sexual orientation, and ethnicity were reported infrequently or in non-inclusive ways. The mean between-condition effect size was small and moderately heterogenous (d = 0.158, 95% CI = 0.079, 0.238, I2 = 46%) and the mean within-condition effect size was large and showed high heterogeneity (dz = 1.147, 95% CI = 0.811, 1.482, - I2 = 96%). The specific drug targeted in the study and whether biological assay-based outcomes were used moderated between-condition CBI efficacy and the inclusion of co-occurring mental health conditions and study publication date moderated within-condition CBI effects. Conclusions. Results provide preliminary data on study context factors associated with effect estimates in United States based clinical trials of CBI for AOD.

Technical and relational process in MI sessions with a sample of Hispanic/Latinx adults who engage in heavy drinking: A latent growth mediation model.

The current study tests the Motivational Interviewing (MI) technical and relational hypotheses in a sample of Hispanic/Latinx adults (N = 276) who engage in heavy alcohol consumption. MI causal theory hypothesizes that therapist use of MI consistent skills (i.e., technical hypothesis) and embodiment of the MI Spirit (i.e., relational hypothesis) will elicit client change talk, which is a putative mechanism of positive client outcome after the session. We tested these associations in a rigorous parallel process latent growth curve mediation modeling framework. The data are from a completed randomized clinical trial of a culturally-adapted (CAMI) versus un-adapted MI targeting hazardous alcohol use and consequences. Results. The unconditional growth models for the mediator (i.e., proportion of change talk relative to sustain talk) and two study outcomes (i.e., percent of heavy drinking days; alcohol-related consequences) showed a linear effect over a 12-month period with a slower rate of growth at later timepoints. Contrary to expectations, the latent growth mediation models did not show relationships between MI-consistent skills (i.e., technical predictor) or latent MI Spirit (i.e., relational indicator) and the slope factor for proportion change talk. The slope factor for proportion change talk was also not associated with the slope factors for percent heavy drinking and consequences over follow-up. Conclusions. In this novel population for MI process analysis, the technical and relational hypotheses were not supported. Studies that are exploratory may be needed to further investigate the causal model in populations that are not often represented in MI process research.

Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study.

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1-week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue-reactivity procedure and alcohol self-administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue-induced saliva output. During the alcohol self-administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild-moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress-induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non-treatment seekers and suggests future treatment-oriented trials should investigate mifepristone in people with AUD.

Practice Makes Perfect: MSW Students Reflect on Skill-Based Teaching Methods in Clinical Social Work Education.

In the current focus-group study, we consider student experiences with and perceptions of teaching methods that involve practice observation, demonstration, and performance assessment and feedback (i.e., skill-based teaching methods). Focus groups included masters of social work students (N = 40) from six universities in the United States. Students were, on average, 34 years of age (range 21 to 58) with 75% female, 20% male, and two non-binary students. Students identified as White (50%), Latinx/Latine (20%), Black (12.5%), and multi-racial (12.2%). A framework-guided content analysis was used, and revealed four broad themes: 1) classroom-based opportunities for practice observation and feedback, 2) field-based opportunities for practice observation and feedback, 3) other methods such as standardized patient simulations and computer simulations, and 4) attitudes about these methods. Experiences with these methods were quite diverse with classroom-based role plays being the most common. Attitudes were generally positive, though lack of authenticity and performance anxiety were perceived as drawbacks. Student reflections on their experiences yielded several teaching recommendations specific to preparation, the nature of the simulated client role, and feedback.

The Relationship Between Drinking Behavior and Conversational Processes During a Brief Alcohol Reduction Intervention for People with HIV.

People with HIV (PWH) frequently engage in unhealthy alcohol use, which can adversely affect antiretroviral adherence and HIV disease progression. Brief interventions based on Motivational Interviewing (MI), including the Brief Negotiated Interview (BNI), can help to reduce drinking. This study examines MI processes observed during a single 15-20 min BNI session delivered by social workers to PWH with unhealthy alcohol use (N = 59) in the context of a stepped care intervention to reduce alcohol consumption. BNI sessions were coded for technical and relational processes encouraged in MI, such as autonomy support, instructive language, and self-exploration. Multiple regression analyses explored the relationship between: (1) Participants' pre-intervention drinking behaviors (weekly drinks and heavy drinking days) and these MI processes, and (2) MI processes and intervention outcomes. Results indicated that PWH who reported more weekly drinks at baseline engaged in less self-exploration, while social workers delivering the BNI used less instructive language for those who reported more heavy drinking days. PWH who engaged in more self-exploration and received more autonomy support had fewer heavy drinking days 6 months after the intervention. These findings suggest the value of providing more opportunities within BNIs to encourage self-exploration, as it may help to enhance intervention efficacy.

How do US orthopaedic surgeons view placebo-controlled surgical trials? A pilot online survey study.

Randomised placebo-controlled trials (RPCTs) are the gold standard for evaluating novel treatments. However, this design is rarely used in the context of orthopaedic interventions where participants are assigned to a real or placebo surgery. The present study examines attitudes towards RPCTs for orthopaedic surgery among 687 orthopaedic surgeons across the USA. When presented with a vignette describing an RPCT for orthopaedic surgery, 52.3% of participants viewed it as 'completely' or 'mostly' unethical. Participants were also asked to rank-order the value of five different types of evidence supporting the efficacy of a surgery, ranging from RPCT to an anecdotal report. Responses regarding RPCTs were polarised with 26.4% viewing it as the least valuable (even less valuable than an anecdote) and 35.7 .% viewing it as the most valuable. Where equipoise exists, if we want to subject orthopaedic surgeries to the highest standard of evidence (RPCTs) before they are implemented in clinical practice, it will be necessary to educate physicians on the value and ethics of placebo surgery control conditions. Otherwise, invasive procedures may be performed without any benefits beyond possible placebo effects.

Discussion of alcohol consequences during a brief motivational intervention session: Comparing those who do and do not increase readiness to change.

The present study was designed to take an inductive, qualitative approach to understanding how discussion of alcohol-related consequences during brief motivational interventions (BMI) relate to readiness to change (RTC) prior to versus at the end of a session. Participants were thirty-four adults (35% female) recruited from the emergency room and enrolled in a randomized clinical trial of a BMI for risky alcohol use and risky sex. Seventeen participants both began and remained low on RTC over the course of the session. We selected 17 additional participants, matched on demographics, but who increased RTC over the session. Transcripts were qualitatively coded and analyzed separately within groups. Among participants who increased their RTC relative to participants who remained low on RTC by BMI end, evaluation of alcohol consequences as negative was more typical. In both groups, several consequences were neutrally evaluated. Many who remained low on RTC attributed consequences to something other than alcohol and/or minimized consequence severity. Study findings highlight the value for clinicians in eliciting and maximizing the importance of subjectively negative recent consequences to perhaps increase heavy drinkers' readiness to decrease heavy alcohol use.

Cognitive-Behavioral Interventions Targeting Alcohol or Other Drug Use and Co-Occurring Mental Health Disorders: A Meta-Analysis.

AIMS: This meta-analysis reviewed 15 clinical trials (18 study sites/arms), examining the efficacy of an integrated cognitive-behavioral intervention (CBI) delivered to individuals with an alcohol or other drug use disorder and a co-occurring mental health disorder (AOD/MHD). Outcomes were alcohol or other drug use and mental health symptoms at post-treatment through follow-up. METHODS: The inverse-variance weighted effect size was calculated for each study and pooled under random effects assumptions. RESULTS: Integrated CBI showed a small effect size for AOD (g = 0.188, P = 0.061; I2 = 86%, τ2 = 0.126, k = 18) and MHD (g = 0.169, P = 0.024; I2 = 58%, τ2 = 0.052, k = 18) outcomes, although only MHD outcomes were statistically significant. Analysis by subgroup suggested that effect magnitude varied by type of contrast condition (integrated CBI + usual care vs. usual care only; integrated CBI vs. a single-disorder intervention), follow-up time point (post-treatment vs. 3-6 months) and primary AOD/MHD diagnosis, although these sub-groups often contained significant residual heterogeneity. In a series of mixed effects, meta-regression models, demographic factors were non-significant predictors of between-study heterogeneity. For AOD outcomes, greater effects were observed in higher quality studies, but study quality was not related to effect size variability for MHD outcomes. CONCLUSIONS: The current meta-analysis shows a small and variable effect for integrated CBI with the most promising effect sizes observed for integrated CBI compared with a single disorder intervention (typically an AOD-only intervention) for follow-up outcomes, and for interventions targeting alcohol use and/or post-traumatic stress disorder. Given the clinical and methodological variability within the sample, results should be considered a preliminary, but important step forward in our understanding of treatment for co-occurring AOD/MHD.

Technology-Delivered Cognitive-Behavioral Interventions for Alcohol Use: A Meta-Analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) has long-standing evidence for efficacy in the treatment of alcohol use, yet implementation in clinical practice has been challenging. Delivery of CBT through technology-based platforms, such as web-based programs and mobile applications, has the potential to provide widespread access to this evidence-based intervention. While there have been reviews indicating the efficacy of technology-based delivery of CBT for various psychiatric conditions, none have focused on efficacy for alcohol use. The current meta-analysis was conducted to fill this research gap. METHODS: Descriptive data were used to characterize the nature of the literature on technology-delivered, CBT-based interventions for alcohol use ("CBT Tech"). Inverse-variance-weighted effect sizes were calculated, and random effects, effect sizes were pooled in 4 subgroups. RESULTS: Fifteen published trials conducted primarily with at-risk or heavy drinkers were identified. Of these studies, 60% explicitly targeted alcohol use moderation. The content of CBT Tech programs varied, ranging from 4 to 62 sessions/exercises, with many programs combining elements of motivational interviewing (47%). With respect to efficacy, CBT Tech as a stand-alone treatment in contrast to a minimal treatment control showed a positive and statistically significant, albeit small effect (g = 0.20: 95% CI = 0.22, 0.38, kes  = 5). When CBT Tech was compared to treatment as usual (TAU), effects were nonsignificant. However, when CBT Tech was tested as an addition to TAU, in contrast to TAU only, the effect size was positive, significant (g = 0.30: 95% CI = 0.10, 0.50, kes  = 7), and stable over 12-month follow-up. Only 2 studies compared CBT Tech to in-person CBT, and this pooled effect size did not suggest superior efficacy. CONCLUSIONS: These results show a benefit for technology-delivered, CBT-based interventions as a stand-alone therapy for heavy drinking or as an addition to usual care in specialty substance use settings.

Naltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta-analysis.

Naltrexone (NTX) has been widely studied for the treatment of alcohol use disorder with overall support for its efficacy. The mechanisms of action of naltrexone are thought to involve attenuation of the hedonic effects of alcohol and potentiation of its aversive effects. In order to provide a quantitative estimate of the effects of naltrexone on subjective response to alcohol, the aims of this meta-analytic review are to examine the effects of naltrexone across four domains of subjective response. Meta-analyses of naltrexone effects on alcohol craving (k = 16, N = 686), stimulation (k = 15, N = 675), sedation (k = 18, N = 777), and negative mood (k = 9, N = 281) suggested that under laboratory conditions and compared with placebo, naltrexone reduces craving (Hedges g = -0.252; SE = 0.054; 95% CI, -0.375 to -0.130; P < 0.01), reduces stimulation (g = -0.223; SE = 0.067; 95% CI, -0.372 to -0.074; P < 0.01), increases sedation (g = 0.251; SE = 0.064; 95% CI, 0.112-0.389; P < 0.01), and increases negative mood (g = 0.227; SE = 0.047; 95% CI, 0.100-0.354; P < 0.01). Results were robust when drinks per month and alcohol dose were added to the models as covariates. The effects of naltrexone varied by severity of alcohol use with medication effects on craving and stimulation being observed in sample of both heavy drinkers and AUD individuals. These results are consistent with the hypothesized mechanisms of action of NTX, although the effects are of small magnitude. This meta-analysis aggregates across multiple human laboratory studies of NTX's effects on subjective response to alcohol, providing a comprehensive summary of a key mechanism of NTX efficacy, namely, alteration of the subjective experience of alcohol.

The role of therapist MI skill and client change talk class membership predicting dual alcohol and sex risk outcomes.

OBJECTIVE: We investigated the technical model of motivational interviewing (MI) in a dual-outcome intervention (i.e., alcohol, sexual risk; N = 164; 57% female). METHOD: We identified latent classes of client change statements, based on the proportion of change talk (CT) over the session. We then examined whether outcomes were related to CT class, and whether the relations between MI skill and outcomes varied by CT class. RESULTS: We found three classes of alcohol-CT and two classes of sexual risk-CT. While CT class membership did not predict outcomes directly, greater therapist MI-consistent skill was associated with fewer heavy drinking days in the increasing alcohol-CT class. For sexual risk outcomes, therapist MI-consistent skill was associated with reduced odds of condomless sex for the low sexual risk-CT class. CONCLUSIONS: The relation of therapist MI consistency to outcomes appears to be a function of client CT during the session.

Do what you say and say what you are going to do: A preliminary meta-analysis of client change and sustain talk subtypes in motivational interviewing.

Objective: This meta-analysis examines the predictive validity of client change language subtypes in motivational interviewing (MI) sessions addressing addictive behavior change. Method: A systematic review identified k = 13 primary studies, contributing 16 MI conditions (N = 1556). The pooled correlation coefficient was used to assess the significance, direction, and strength of seven language subtypes (i.e., reason, desire, need, ability, commitment, taking steps, and other) by three valences (i.e., frequency positive or change talk, frequency negative or sustain talk, and proportion change talk) and their relationship to subsequent engagement in addictive behavior. Results: For frequency measures, more sustain talk related to reason, desire, ability, and other were associated with more addictive behavior at follow up. Other change talk was associated with MI outcomes but in an unexpected direction (i.e., more addictive behavior). Proportion measures showed more proportion change talk-reason and -other statements were associated with less addictive behavior at follow up. Sensitivity analyses indicated some heterogeneity and instability of effect sizes, but no evidence of publication bias. Conclusions: This preliminary meta-analysis suggests that aggregate measures of change and sustain talk are comprised of statement subtypes that are not equally meaningful in predicting outcome following MI for addictive behavior change.

Overcoming the "Valley of Death" in Medications Development for Alcohol Use Disorder.

As the development of novel pharmacotherapies for alcohol use disorder (AUD) has been slow, the discovery and testing of more efficacious pharmacotherapies for AUD represent a high priority research area. In fact, the transition from preclinical to clinical testing of novel compounds has been termed the "valley of death" in medications development. One key obstacle consists of the lack of an articulated set of goals for each stage of medications development. Specifically, the knowledge outputs required to make the transition from safety testing, to early efficacy detection, to confirming clinical efficacy remain unclear, and this is despite a great deal of interest and substantial financial investment in developing novel therapeutics for AUD. This qualitative critical review seeks to draw parallels and lessons from the well-established stage model for behavioral therapies research with alcohol and other substance use disorders and to apply these insights into AUD pharmacotherapy development. We argue that human laboratory models and/or pilot randomized controlled trials should serve as intermediaries in the transition from preclinical studies to large, and costly, randomized controlled efficacy trials. The relative strengths and weaknesses of pilot clinical trials versus human laboratory studies for bridging the "valley of death" are discussed and explored via a Monte Carlo data simulation study. Multiple permutations of suitable research designs informed by the behavioral therapies development model are discussed with the overall goal of promoting consilience and maximizing efficiency across all phases of clinical testing of novel AUD pharmacotherapies.

Brief Motivational Intervention for Underage Young Adult Drinkers: Results from a Randomized Clinical Trial.

BACKGROUND: While there is a substantial literature on the efficacy of brief motivational intervention (BMI) for college student drinkers, research has focused less on young adults who do not attend a 4-year college, despite their elevated risk for excessive alcohol use and associated harmful consequences. METHODS: This randomized controlled trial (NCT01546025) compared the efficacy of BMI to a time-matched attention control intervention (relaxation training [REL]) for reducing alcohol consumption and related negative consequences in an underage young adult sample. BMI was tailored to the developmental transition out of high school for young adults who were not immediately planning to enroll in a 4-year college. Non-treatment-seeking underage drinkers who reported past-month heavy drinking (N = 167; ages 17 to 20; 42% female; 59% non-Hispanic White) were randomly assigned to receive a single session of BMI or REL. Outcomes were evaluated 6 weeks and 3 months postintervention via in-person assessments. RESULTS: Generalized estimating equation models provided strong support for the efficacy of BMI for reducing harmful drinking in these young adults. Compared to REL, and after controlling for baseline covariates including gender, those who received BMI subsequently reported significantly fewer average drinks per week, percent drinking days, percent heavy drinking days, lower peak and typical estimated blood alcohol concentration on drinking days, and fewer adverse consequences of drinking (all ps < 0.05). These between-group effects did not weaken over the course of the 3-month follow-up period. CONCLUSIONS: These findings demonstrate an efficacious approach to tailoring BMI for non-college-attending young adults. Future research should replicate and extend these findings over a longer follow-up period.

Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later.

BACKGROUND: The current review revisits the article entitled: "Active Ingredients: How and Why Evidence-Based Alcohol Behavioral Treatment Interventions Work" published in Alcoholism: Clinical and Experimental Research. This work summarized proceedings from a 2004 Symposium of the same name that was held at the Annual Meeting of the Research Society on Alcoholism (RSA). A decade has passed, which provides occasion for an evaluation of progress. In 2014, an RSA symposium titled Active Treatment Ingredients and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later did just that. METHODS: The current review revisits state-of-the-art research on the 3 treatments examined 10 years ago: cognitive behavioral therapy, alcohol behavior couples therapy, and 12-step facilitation. Because of its empirically validated effectiveness and robust research agenda on the study of process outcome, motivational interviewing has been selected as the fourth treatment modality to be discussed. For each of these 4 treatments, the reviewers provide a critical assessment of current theory and research with a special emphasis on key recommendations for the future. RESULTS: Noteworthy progress has been made in identifying active ingredients of treatments and mechanisms of behavior change in these 4 behavioral interventions for alcohol and other drug use disorders. Not only have we established some of the mechanisms through which these evidence-based treatments work, but we have also uncovered some of the limitations in our existing frameworks and methods. CONCLUSIONS: Further progress in this area will require a broader view with respect to conceptual frameworks, analytic methods, and measurement instrumentation.

Influence of counselor characteristics and behaviors on the efficacy of a brief motivational intervention for heavy drinking in young men--a randomized controlled trial.

BACKGROUND: Brief motivational intervention (BMI) has shown promising results to reduce alcohol use in young adults. Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation. Particularly, little attention has been given to counselor influence on treatment mechanisms. METHODS: We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men (age 20) screened as hazardous drinkers. Participants were randomly allocated to (i) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics (gender, professional status, clinical experience, and motivational interviewing [MI] experience) or (ii) a control group receiving assessment only. Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy. Then, the influence of counselors' characteristics (i.e., gender, professional status, clinical experience, MI experience, BMI attitudes, and expectancies) and within-session behaviors (i.e., measured by the Motivational Interviewing Skill Code) on outcome was tested in regression analyses. RESULTS: There was a significant (p = 0.02) decrease in alcohol use among the BMI group compared to the control group. Counselors that were male, more experienced, that had more favorable BMI attitudes and expectancies, higher MI skills, but surprisingly less MI-consistent behaviors, had significantly better outcomes than the control group while their counterparts did not. CONCLUSIONS: The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males. Moreover, BMI effect was related to interindividual differences among counselors, and results therefore provide recommendations for BMI training and implementation with similar populations.

Defining the therapeutic relationship in the context of alcohol use, other drug use, and behavior change: Principles and practices.

OVERVIEW: This article contributes to knowledge and practice of core processes that are shared by evidence-based alcohol or other drug (AOD) therapies. It is the fourth in a series with this aim, and here we discuss perhaps the most universally acknowledged ingredient of effective therapy - the therapeutic relationship. We consider various related terms and definitions in the literature, but in the present review, we offer a definition that underscores the context of behavior change. METHOD: This study conducted a literature review and qualitative content analysis to derive a set of principles and practices for facilitating and maintaining the therapeutic relationship. The sources for this review included government-issued practice guidelines, therapy manuals or books, demonstration videos, and peer-reviewed articles (61 sources). The content analysis was performed in NVIVO, and reliability analysis showed moderate agreement between raters (kappa = 0.60). RESULTS: Six principles and 16 practices were identified. The distribution of principles and practices could be broken into three categories: 1) the facilitation of client behavior change mechanisms (i.e., self-determination, motivation, self-efficacy), 2) partnership considerations (e.g., goal and task alignment), and 3) therapist interpersonal skills (e.g., empathy). CONCLUSIONS: The therapeutic relationship is foundational to the behavior change process. We frame it as a combination of broader interpersonal considerations and attention to key mechanisms of client behavior change. The present work provides a novel resource for trainees, clinicians, and clinical supervisors interested in fostering therapy relationships with clients in AOD or other behavior change settings.