Therapeutic Content of Mobile Phone Applications for Substance Use Disorders: An Umbrella Review.

Mobile phone applications (MPAs) for substance use disorder (SUD) treatment are increasingly used by patients. Although pilot studies have shown promising results, multiple previous systematic reviews noted insufficient evidence for MPA use in SUD treatment-many of the previously published reviews evaluated different trials. Subsequently, we aimed to conduct an umbrella review of previously published reviews investigating the efficacy of MPAs for SUD treatment, excluding nicotine/tobacco because umbrella reviews have been done in this population and the nicotine/tobacco MPA approach often differs from SUD-focused MPAs. No previous reviews have included a statistical meta-analysis of clinical trials to quantify an estimated overall effect. Seven reviews met inclusion criteria, and 17 unique studies with available data were taken from those reviews for the meta-analysis. Overall, reviews reported a lack of evidence for recommending MPAs for SUD treatment. However, MPA-delivered recovery support services, cognitive behavioral therapy, and contingency management were identified across multiple reviews as having promising evidence for SUD treatment. Hedges g effect size for an MPA reduction in substance use-related outcomes relative to the control arm was insignificant (0.137; 95% CI, -0.056 to 0.330; P=.16). In subgroup analysis, contingency management (1.29; 95% CI, 1.088-1.482; τ 2=0; k=2) and cognitive behavioral therapy (0.02; 95% CI, 0.001-0.030; τ 2=0; k=2) were significant. Although contingency management's effect was large, both trials were small (samples of 40 and 30). This review includes an adapted framework for the American Psychiatric Association's MPA guidelines that clinicians can implement to review MPAs critically with patients.

Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study.

BACKGROUND: Sex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset. METHODS: We retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198,058 males; 250,830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking. RESULTS: AD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls (padjusted<0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls (padjusted<0.001). These differences remained after accounting for current drinking frequency (p < 0.001). SHBG moderated TT's effect on AD in males (pinteraction<0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males (p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males (p < 0.001). CONCLUSIONS: Testosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations.

Factors Having an Impact on Relapse and Survival in Transplant Recipients With Alcohol-Induced Liver Disease.

OBJECTIVE: To assess the impact of standardized pretransplant alcohol abstinence and treatment guidelines on liver transplant outcomes. METHODS: This study assessed the posttransplant relapse and survival associated with a pretransplant guideline mandating alcohol abstinence, addiction treatment, and Alcoholics Anonymous (AA) attendance. This retrospective cohort study included liver recipients with alcohol-induced liver disease transplanted between January 1, 2000, and December 31, 2012, at a Midwest transplant center. Cox regression models tested for associations between pretransplant treatment, demographic and clinical characteristics, and outcome measures. RESULTS: Of 236 liver recipients (188 [79.7%] male; 210 [89%] white; mean follow-up, 88.6±55.0 months), 212 (90.2%) completed pretransplant treatment and 135 (57.2%) attended AA weekly. At 5 years, 16.3% and 8.2% had relapsed to any alcohol use and to high-dose drinking, respectively. Smoking during the 6 months before transplant was associated with any relapse (P=.0002) and high-dose relapse (P<.0001), and smoking at transplant was associated with death (P=.001). High-dose relapse was associated with death (hazard ratio, 3.5; P<.0001). CONCLUSION: A transplant center with a guideline requiring abstinence, treatment, and AA participation experienced lower posttransplant relapse rates from those previously reported in comparable large US transplant programs. Smoking cessation may further improve posttransplant outcomes.

Evidence-Based Pharmacotherapies for Alcohol Use Disorder: Clinical Pearls.

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Correlations between sex-related hormones, alcohol dependence and alcohol craving.

BACKGROUND: Sex-related differences in the susceptibility, progression, and treatment response in alcohol-dependent subjects have been repeatedly reported. In this study, we aimed to investigate the associations of the sex-related hormone/protein levels with alcohol dependence (AD) and alcohol craving in male and female subjects. METHODS: Plasma sex-related hormones (estradiol, estrone, total testosterone, progesterone, follicle stimulated hormone [FSH], luteinizing hormone), and sex hormone binding globulin were measured by mass spectrometry or automated immunoassays from 44 recently-abstained subjects (29 males and 15 females; mean age = 45.9 ± 15.6) meeting DSM-IV-TR criteria for AD and 44 age-, sex- and race-matched non-AD controls. Conditional logistic regression was conducted to examine the association of sex-related hormone and protein levels with AD risk, accounting for matching variables. Their associations with alcohol craving scales (Penn Alcohol Craving Scale and Inventory of Drug-Taking Situations) were assessed in AD subjects. RESULTS: Plasma FSH level was significantly higher in AD males (10.3 ± 9.8 IU/L) than control males (8.0 ± 15.9 IU/L; p = 0.005, pcorrected = 0.035). We also found a significant inverse correlation of FSH level with propensity to drink in negative emotional situations (Spearman's rho=-.540; p = 0.021) and positive correlations between progesterone level and craving intensity (Spearman's rho=.464; p = 0.020) and between total testosterone level and propensity to drink under temptations (adjusted for no-drinking days; ß=6.496; p = 0.041) in AD males. CONCLUSIONS: These results suggest that FSH, progesterone, and testosterone levels may be associated with AD and alcohol craving in AD males. Future research is needed to replicate these findings and investigate the underlying biological mechanisms.

Sex hormones in alcohol consumption: a systematic review of evidence.

Sex hormones play an important role in establishing sex-distinctive brain structural and functional variations that could contribute to the sex differences in alcohol consumption behavior. Here, we systematically reviewed articles that studied sex hormone impacts on alcohol consumption and alcohol use disorder (AUD). An extensive literature search conducted in MEDLINE, PubMed, Scopus and CINAHL databases identified 776 articles, which were then evaluated for pre-specified criteria for relevance and quality assurance. A total of 50 articles, including 19 human studies and 31 animal studies, were selected for this review. Existing evidence supports the association of increased testosterone level and increased risk for alcohol use and AUD in males but results are inconclusive in females. In contrast, the evidence supports the association of increased estrogen level and increased alcohol use in females, with mixed findings reported in males. Much less is known about the impact of progestins on alcohol use and misuse in human subjects. Future observational and experimental studies conducted in both sexes with a comprehensive hormone panel are needed to elucidate the impact of the interplay between various sex hormone levels during various developmental stages on alcohol use-related phenotypes and AUD.

Female smokers have the highest alcohol craving in a residential alcoholism treatment cohort.

BACKGROUND: Cigarette smoking among female and male alcoholics has not been extensively studied as a factor related to intensity of alcohol craving during residential treatment and corresponding sobriety length. METHODS: This retrospective cohort study assessed self-reported sobriety outcomes in patients with alcohol dependence at 3-month intervals over 12 months after completion of a 30-day residential treatment program. Demographic and clinical variables were collected including smoking status, alcohol craving utilizing the Penn Alcohol Craving Scale (PACS), and alcohol relapse. Statistical analyses included Chi-square, ANOVA, Tukey's test, Kaplan-Meier plots and Cox proportional hazards models as appropriate. RESULTS: Of the 761 alcohol-dependent study subjects, 355 (47%) were current smokers. Alcohol craving intensity was higher in smoking females compared to nonsmoking females (p=0.0096), smoking males (p<0.0001), and nonsmoking males (p<0.0001). Smoking status-by-sex interaction was not associated with post-treatment relapse. After controlling for other variables, higher PACS scores at admission were associated with higher probability of relapse (p=0.0003). CONCLUSIONS: In this study, female alcoholic smokers experienced the highest level of alcohol craving in an alcohol treatment setting. Interestingly, this did not translate into higher rates of post-treatment relapse. Further research is warranted to explore the neurobiological basis for sex differences in this highly prevalent comorbidity.

Change in consumption patterns for treatment-seeking patients with alcohol use disorder post-bariatric surgery.

OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1±0.4 vs. 25.0±1years old, p=0.002). On average, RYGB patients reported resuming alcohol consumption 1.4±0.2years post-surgery, meeting criteria for AUD at 3.1±0.5years and seeking treatment at 5.4±0.3years postoperatively. Pre-surgical drinks per day were significantly fewer compared to post-surgical consumption [2.5±0.4 vs. 8.1±1.3, p=0.009]. Prior to admission, RYGB patients reported fewer drinking days per week vs. controls (4.7±0.3 vs. 5.5±1.8days, p=0.02). Neither RYGB, gender, age nor BMI was associated with differential drinking patterns. CONCLUSION: The results of this study suggest that some patients develop progressive AUD several years following RYGB. This observation has important clinical implications, calling for AUD-preventive measures following RYGB. Further large-scale longitudinal studies are needed to clarify the association between RYGB and AUD onset.

Functional role of the polymorphic 647 T/C variant of ENT1 (SLC29A1) and its association with alcohol withdrawal seizures.

BACKGROUND: Adenosine is involved in several neurological and behavioral disorders including alcoholism. In cultured cell and animal studies, type 1 equilibrative nucleoside transporter (ENT1, slc29a1), which regulates adenosine levels, is known to regulate ethanol sensitivity and preference. Interestingly, in humans, the ENT1 (SLC29A1) gene contains a non-synonymous single nucleotide polymorphism (647 T/C; rs45573936) that might be involved in the functional change of ENT1. PRINCIPAL FINDINGS: Our functional analysis showed that prolonged ethanol exposure increased adenosine uptake activity of mutant cells (ENT1-216Thr) compared to wild-type (ENT1-216Ile) transfected cells, which might result in reduced extracellular adenosine levels. We found that mice lacking ENT1 displayed increased propensity to ethanol withdrawal seizures compared to wild-type littermates. We further investigated a possible association of the 647C variant with alcoholism and the history of alcohol withdrawal seizures in subjects of European ancestry recruited from two independent sites. Analyses of the combined data set showed an association of the 647C variant and alcohol dependence with withdrawal seizures at the nominally significant level. CONCLUSIONS: Together with the functional data, our findings suggest a potential contribution of a genetic variant of ENT1 to the development of alcoholism with increased risk of alcohol withdrawal-induced seizures in humans.