Larissa L. Loukianova

Alcohol craving as a predictor of relapse.

BACKGROUND AND OBJECTIVES Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment. METHODS The study cohort included 314 alcohol-dependent subjects. Associations between relapse after discharge, PACS score, and clinical variables were investigated using time-to-event analyses. The primary analysis, based on the intent-to-treat principle, presumed relapse in those declining follow-up or not responding to contact attempts. Secondary analysis utilized data from 226 subjects successfully contacted after discharge with a median follow-up time of 365 days. RESULTS The intent-to-treat analysis demonstrated that relapse was associated with higher level of craving at admission (p= .002) and discharge (p < .001). The analysis of data from patients successfully contacted after discharge led to similar results. A multivariable analysis indicated that relapse rates increased as PACS scores increased, and a higher discharge PACS score was significantly associated with relapse (p= .006) even after adjusting for covariates. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE This study demonstrates that higher PACS scores at the time of admission and discharge are associated with relapse following residential addiction treatment. These data support the role of craving in relapse and the utility of craving measurement as a clinical guide in assessing relapse risk.

Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate

Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10−5). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.

Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

A retrospective study of gender differences in depressive symptoms and risk of relapse in patients with alcohol dependence.

BACKGROUND AND OBJECTIVES The aim of this study was to investigate potential gender differences in situations associated with heavy alcohol drinking. METHODS Data from 395 alcohol dependent patients participating in the Mayo Clinic Intensive Addiction Program were evaluated. Each participant completed the inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS), patient health questionnaire (PHQ-9), and/or Beck depression inventory (BDI). Gender differences in IDTS scores representing three domains (negative, positive, and temptation) of situations associated with heavy alcohol use were examined. RESULTS Women with alcohol dependence report a higher frequency of heavy drinking in unpleasant emotional (IDTS negative scores mean ± SD women vs. men: 52.3 ± 22.1 vs. 43.8 ± 21.8; p = .0006), and as a result of temptation (IDTS temptation scores mean ± SD women vs. men: 40.4 ± 23.0 vs. 35.3 ± 20.8; p = .035). Upon admission, women also scored significantly higher on depressive symptoms as measured by the BDI (23.4 ± 11.4 vs. 18.2 ± 9.8, p < .001). After controlling for depressive symptom severity as a covariate, the IDTS gender differences were no longer significant. CONCLUSION AND SCIENTIFIC SIGNIFICANCE Our results suggest that unpleasant or temptation based emotional situations are a vulnerability risk factor for heavy drinking particularly in females. This risk appears to be at least partially driven by depressive symptom burden. Future research is needed to further investigate this finding.

Gender differences in the relationship between depressive symptoms and cravings in alcoholism.

This study examines the clinical correlates of alcohol craving in men and women self-referred for addiction treatment. Admission clinical data from patients participating in the Mayo Clinic 1-month Intensive Addictions Program were evaluated. Women had higher BDI and PACS scores compared with men in both the entire cohort and Dual Diagnoses group. Alcohol-dependent females had the most marked correlation between BDI and PACS (rho= .78). Further prospective study is encouraged to evaluate whether depressive symptoms and concomitant alcohol cravings in women are a marker for relief cravings and, as such, a target symptom for treatment intervention.

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.

Association of GATA4 sequence variation with alcohol dependence

To further explore reports of association of alcohol dependence and response to acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol‐dependent cases and 1248 controls. We tested for association of alcohol dependence with the 11 SNPs individually and performed a global test for association using a principle components analysis. Our analyses demonstrate significant association between GATA4 and alcohol dependence at the gene level (P = 0.009) but no association with rs13273672. Further studies are needed to identify potential causal GATA4 variation(s) and the functional mechanism(s) contributing to this association.

Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states

Abstract Background and Aims Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life‐time diagnoses of major depressive disorder (MDD), substance‐induced depression (SID), anxiety disorder (AnxD) and substance‐induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Design Secondary analyses of baseline data collected in a single‐arm study of pharmacogenetic predictors of acamprosate response. Setting Academic medical center and affiliated community‐based treatment programs in the American upper mid‐west. Participants A total of 287 males and 156 females aged 18–80 years, meeting DSM‐IV criteria for alcohol dependence. Measurements The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). Findings The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect (P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = −6.6, P = 0.091). Conclusions There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance‐induced depression appears to have a sex‐specific effect on the increased risk for drinking in negative emotional situations in males.

Trazodone and alcohol relapse: a retrospective study following residential treatment.

Trazodone is one of the most commonly prescribed hypnotic medications in patients with sleep disturbances in alcohol recovery. A recent study concluded that treating insomnia with trazodone in patients with alcohol dependence might impede improvements in alcohol consumption and lead to increased drinking when trazodone is stopped. We set out to investigate the relationship between trazodone use during alcoholism treatment and relapse rates in patients who were discharged from a residential alcohol treatment program. We retrospectively reviewed records of patients with a diagnosis of alcohol dependence in a residential addiction treatment center from 2005 to 2008 and analyzed the association of trazodone use at discharge and alcohol relapse at 6 months. We also assessed the association between trazodone use and relapse at 6 months adjusting for sex, drug dependence, nonsubstance use Axis I psychiatric diagnoses, patient self-report of difficulties with sleep, and anti-dipsotropic medication use at discharge and evaluated pair-wise interactions of trazodone use with the adjustment variables. Of 283 patients eligible for inclusion, 85 (30%) were taking trazodone at discharge. Older age, self-reported sleep problems, and having a nonsubstance use Axis I psychiatric diagnosis were associated with trazodone use. After discharge, 170 (60%) subjects responded to follow-up efforts. Neither intent to treat nor responder only analysis revealed any association between trazodone use and relapse. Our retrospective study of a complex patient population discharged from a residential treatment setting did not find an association between trazodone use at discharge and relapse rates at 6 months.

Assessment of family history of substance abuse for preventive interventions with patients experiencing chronic pain: A quality improvement project.

This quality improvement project demonstrates that RN Care Managers, in a chronic pain programme, can assess for a family history of substance abuse in 5–10 min. Information informs treatment based on specific high risk criteria. Benefits include heightened awareness of the genetic and environmental risks associated with a family history of substance abuse, an opportunity to participate in motivational interventions to prevent or minimize consequences of substance use disorders, and likely substantial overall health-care cost savings.This quality improvement project demonstrates that RN Care Managers, in a chronic pain programme, can assess for a family history of substance abuse in 5-10 min. Information informs treatment based on specific high risk criteria. Benefits include heightened awareness of the genetic and environmental risks associated with a family history of substance abuse, an opportunity to participate in motivational interventions to prevent or minimize consequences of substance use disorders, and likely substantial overall health-care cost savings.