Examining cocaine use reductions and long-term outcomes in two clinical trials of continuing care for cocaine dependence.

BACKGROUND: There is a need to identify clinically meaningful non-abstinent endpoints for cocaine use disorder (CUD) clinical trials. In this study, we sought to replicate and extend prior work validating reductions in cocaine use frequency levels as an endpoint by examining associations between reductions in cocaine use frequency and long-term functioning outcomes. METHODS: We conducted a secondary analysis of two randomized clinical trials (N = 445; 77.5 % male; mean age = 42.18 years; 86.5 % Black, 10.8 % non-Hispanic white) that evaluated telephone-based continuing care for a 12- and 24-month period. Cocaine use frequency levels, measured with the Timeline Followback, were (1) abstinence (no past-month cocaine use), (2) low-frequency use (1-4 days of use/month), and (3) high-frequency use (5+ days of use/month). RESULTS: Among those who completed the 12-month follow-up (n = 392), most reduced from high-frequency use at baseline to abstinence at the 12-month follow-up (n = 243; 62.0 %). An additional 21.2 % (n = 83) reported either high-to-low-frequency use (n = 35; 8.9 %) or low use-to-abstinence (n = 48; 12.2 %); 16.8 % of participants (n = 66) did not change or increased their cocaine frequency level. Compared to those who had no change/increases in frequency levels, at least a one-level reduction from baseline to 12-month follow-up (i.e., high-to-low-frequency use, high-to-abstinence, low-to-abstinence) was concurrently associated with lower levels of negative consequences at the 12-month follow-up and prospectively with lower levels of cocaine use and consequences at 24-month follow-up, with effect sizes in the medium-to-large range. Those who reduced to abstinence generally had fewer drug use consequences at the 12-month follow-up than those who reduced to a low-frequency level; however, these groups did not significantly differ on any outcomes at the 24-month follow-up. CONCLUSIONS: Categorical reductions in cocaine use frequency levels, including those short of abstinence, are associated with less cocaine use and lower problem severity up to two years following treatment entry. Low-frequency cocaine use following the initial treatment phase does not appear to forebode worsening functioning, such as escalations in cocaine use.

Reductions in World Health Organization Risk Drinking Level Are Associated With Reductions in Alcohol Use Disorder Diagnosis and Criteria: Evidence From an Alcohol Pharmacotherapy Trial.

OBJECTIVES: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria. METHODS: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346). Participants received gabapentin enacarbil extended release or placebo for 6 months. The timeline follow-back was used to assess WHO risk drinking level reductions, and the Mini-International Neuropsychiatric Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria at baseline (past year) and end of treatment (past month). RESULTS: Most participants (80.1%) achieved at least a 1-level reduction in the WHO risk drinking levels from baseline to end of treatment, and nearly half of participants (49.8%) achieved at least a 2-level reduction. At least a 1-level reduction or at least a 2-level reduction in WHO risk drinking level predicted lower odds of an active AUD diagnosis (1-level: odds ratio, 0.74 [95% confidence interval (CI), 0.66-0.84]; 2-level: odds ratio, 0.71 [95% CI, 0.64-0.79]) and fewer AUD criteria (1-level: B, -1.66 [95% CI, -2.35 to -0.98]; 2-level: B, -1.76 [95% CI, -2.31 to -1.21]) at end of treatment. CONCLUSIONS: World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Designing and testing treatments for alcohol use disorder.

This chapter provides a succinct overview of several recommendations for the design and analysis of treatments for AUD with a specific focus on increasing rigor and generalizability of treatment studies in order to increase the reach of AUD treatment. We recommend that researchers always register their trials in a clinical trial registry and make the protocol accessible so that the trial can be replicated in future work, follow CONSORT reporting guidelines when reporting the results of the trial, carefully describe all inclusion and exclusion criteria as well as the randomization scheme, and always use an intent to treat design with attention to analysis of missing data. In addition, we recommend that researchers pay closer attention to recruitment and engagement strategies that increase enrollment and retention of historically marginalized and understudied populations, and we end with a plea for more consideration of implementation science approaches to increase the dissemination and implementation of AUD treatment in real-world settings.

Reductions in WHO risk drinking levels correlate with alcohol craving among individuals with alcohol use disorder.

BACKGROUND: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery. Whether reductions in drinking during AUD treatment are associated with reductions in craving has not been well examined. METHODS: We conducted secondary analyses of data from three AUD clinical trials (N's= 1327, 346, and 200). Drinking reductions from baseline to the end of treatment were measured as changes in World Health Organization (WHO) risk drinking levels; alcohol craving was measured using validated self-report measures. Regression analyses tested whether drinking reductions were associated with end-of-treatment craving reductions; moderation analyses tested whether associations between drinking reduction and end-of-treatment craving differed across AUD severity. RESULTS: Reductions of at least 1 or at least 2 WHO risk drinking levels were associated with lower craving (all p's < 0.05). Results were substantively similar after removing abstainers at the end-of-treatment. Associations between drinking reductions and craving were generally not moderated by AUD severity. CONCLUSIONS: Individuals with WHO risk drinking level reductions reported significantly lower craving, as compared to those who did not achieve meaningful reductions in drinking. The results demonstrate the utility of WHO risk drinking levels as AUD clinical trial endpoints and provide evidence that drinking reductions mitigate craving.

Association Between Religious Salience and Past-Year Substance Use by Sexual Identity and Sex Among Adults in the United States.

Purpose: We examined if associations between religious salience and substance use outcomes differed by sexual identity and sex in a nationally representative sample of adults in the United States. Methods: Using data from the 2019 National Survey on Drug Use and Health (N = 41,216 adults), logistic regression models tested whether sexual identity and sex moderated the associations between religious salience (agreement on the importance of religious beliefs) and past-year alcohol and drug use and use disorders. Results: Religious salience reduced risk of alcohol use disorder, drug use, and drug use disorder for heterosexual, but not lesbian, gay, and bisexual (LGB), individuals. Three-way interactions indicated that religious salience was more protective against alcohol use and drug use and use disorder for bisexual men than bisexual women. Conclusions: Heterosexism common in dominant religious institutions in the United States might hamper the protective effect of religiosity on substance use for LGB individuals.

Examining Associations Between Negative Affect and Substance Use in Treatment-Seeking Samples: A Review of Studies Using Intensive Longitudinal Methods.

Purpose of Review: Understanding dynamic relationships between negative affect and substance use disorder (SUD) outcomes, including craving, may help inform adaptive and personalized interventions. Recent studies using intensive longitudinal methods were reviewed to examine relationships between negative affect and the outcomes of either craving or substance use during and following SUD treatment. Recent Findings: Results on associations between negative affect and craving/substance use were mixed and difficult to synthesize, given methodological differences across studies. The strength and direction of these relationships varied across outcomes, subgroups, contexts, and time course. Summary: The current literature is mixed concerning negative affect and craving/substance use associations during and following SUD treatment. Researchers should increasingly recruit diverse individuals, for example, samples of varying racial and ethnic backgrounds and those reporting co-occurring disorders and polysubstance use. Experimental, qualitative, and person-specific methods will improve our understanding of relationships between negative affect and substance-related outcomes during SUD treatment.