The potential utility of drinking motive questions to screen at-risk drinking in socially anxious patients.

BACKGROUND: Drinking motives are thought to be important mediators of the relationship between social anxiety and alcohol use. This project evaluates whether specific drinking motives accurately reflect alcohol dependence. If so, brief questions about drinking motives could serve as valuable alcohol screening tools with socially anxious patients. METHODS: This investigation was a secondary analysis of an existing data set of 83 subjects with social anxiety disorder and at-risk alcohol use. The relationship between Drinking Motives Questionnaire (DMQ-R-5) subscales and alcohol dependence was evaluated. RESULTS: Coping-Depression was the only subscale that contributed to the unique prediction of a diagnosis of alcohol dependence. Additionally, two items (i.e. "to cheer up when you're in a bad mood" and "to forget painful memories") predicted a diagnosis of alcohol dependence above and beyond their association with each other. CONCLUSIONS: Among patients with social anxiety, two specific questions on the DMQ-R-5 could provide a useful screen for health professionals to predict alcohol dependence. It may be fruitful to specifically target the motives of "to cheer up when you're in a bad mood" and "to forget painful memories" when providing advice during brief interventions.

Gender differences in alcohol treatment: an analysis of outcome from the COMBINE study.

BACKGROUND: Relatively few studies have examined gender differences in the effectiveness of specific behavioral or pharmacologic treatment of alcohol dependence. The aim of this study is to assess whether there were gender differences in treatment outcomes for specific behavioral and medication treatments singly or in combination by conducting a secondary analysis of public access data from the national, multisite NIAAA-sponsored COMBINE study. METHODS: The COMBINE study investigated alcohol treatment among 8 groups of patients (378 women, 848 men) who received medical management (MM) with 16 weeks of placebo, naltrexone (100 mg/day), acamprosate (3 g/day), or their combination with or without a specialist-delivered combined behavioral intervention. We examined efficacy measures separately for men and women, followed by an overall analysis that included gender and its interaction with treatment condition in the analyses. These analyses were performed to confirm whether the findings reported in the parent trial were also relevant to women, and to more closely examine secondary outcome variables that were not analyzed previously for gender effects. RESULTS: Compared to men, women reported a later age of onset of alcohol dependence by approximately 3 years, were significantly less likely to have had previous alcohol treatment, and drank fewer drinks per drinking day. Otherwise, there were no baseline gender differences in drinking measures. Outcome analyses of 2 primary (percent days abstinent and time to first heavy drinking day) and 2 secondary (good clinical response and percent heavy drinking days) drinking measures yielded the same overall pattern in each gender as that observed in the parent COMBINE study report. That is, only the naltrexone by behavioral intervention interaction reached or approached significance in women as well as in men. There was a naltrexone main effect that was significant in both men and women in reduction in alcohol craving scores with naltrexone-treated subjects reporting lower craving than placebo-treated subjects. CONCLUSIONS: This gender-focused analysis found that alcohol-dependent women responded to naltrexone with COMBINE's Medical Management, similar to the alcohol-dependent men, on a wide range of outcome measures. These results suggest that clinicians can feel comfortable prescribing naltrexone for alcohol dependence in both men and women. In this study, it is also notable that fewer women than men reported receiving any alcohol treatment prior to entry into the COMBINE study. Of note, women tend to go to primary health care more frequently than to specialty substance abuse programs for treatment, and so the benefit we confirm for women of the naltrexone and MM combination has practical implications for treating alcohol-dependent women.

A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.

INTRODUCTION: Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. METHODS: One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratings > or =10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels. RESULTS: CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. CONCLUSIONS: Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

A complex relationship between co-occurring social anxiety and alcohol use disorders: what effect does treating social anxiety have on drinking?

BACKGROUND: Individuals with social anxiety disorder and co-occurring alcohol problems report using alcohol to cope with anxiety symptoms. Interventions that reduce both social anxiety and drinking are needed. Paroxetine, an FDA-approved medication to treat social anxiety disorder, reduces anxiety in individuals with co-occurring alcohol problems. OBJECTIVES: To examine whether effective treatment of social anxiety with paroxetine reduces drinking in dual-diagnosed individuals who endorse using alcohol to cope. METHODS: A 16-week, double-blind, randomized controlled trial of paroxetine was conducted. Participants (placebo n = 22; paroxetine n = 20) met DSM-IV diagnostic criteria for social anxiety disorder and alcohol abuse or dependence. Participants were seeking treatment for social anxiety, not for the alcohol problem. Alcohol use outcomes were measured with conventional quantity/frequency measures and novel measures of drinking to cope. RESULTS: Paroxetine improved social anxiety more than placebo. Paroxetine reduced self-reported reliance on alcohol for self-medication purposes, but was not different than placebo in changing quantity and frequency drinking or the proportion of drinking days that were identified as coping-related. Exploratory analyses revealed that for the placebo group, drinking during the trial was correlated with social anxiety severity, whereas for the paroxetine-treated group, drinking was uncoupled from social anxiety severity. CONCLUSIONS: Successfully treating social anxiety symptoms with paroxetine does not reduce drinking in dual-diagnosed individuals who are not seeking treatment for alcohol problems. Paroxetine does, however, reduce reliance on alcohol to engage in social situations, and may change the reasons why one drinks (such that drinking occurs for other reasons besides coping with anxiety). These results have implications for staging of social anxiety and alcohol treatment in individuals with the co-occurring disorders presenting to a mental health or primary care provider.

Paroxetine reduces social anxiety in individuals with a co-occurring alcohol use disorder.

Patients with social anxiety disorder who are seen in clinical practice commonly have additional psychiatric comorbidity, including alcohol use disorders. The first line treatment for social anxiety disorder is selective-serotonin-reuptake-inhibitors (SSRIs), such as paroxetine. However, the efficacy of SSRIs has been determined with studies that excluded alcoholics. Forty two subjects with social anxiety and a co-occurring alcohol use disorder participated in a 16-week, double-blind, placebo-controlled clinical trial to determine the efficacy of paroxetine for social anxiety in patients with co-occurring alcohol problems. Paroxetine was superior to placebo in reducing social anxiety, as measured by the Liebowitz Social Anxiety Scale total and subscale scores and additional measures of social anxiety. This study provides the first evidence-based recommendation for the use of an SSRI to treat social anxiety in this patient population.

Alcohol outcome expectancies and drinking to cope with social situations.

Repeated use of alcohol as a coping strategy to reduce anxiety or discomfort increases one's risk of developing alcohol dependence. Previous studies have found alcohol outcome expectancies (AOE) strongly predict drinking behavior, in general, and also are related to drinking to cope. The purpose of the current study was to examine AOE that may be related to drinking to cope with discomfort in social situations. It was hypothesized that positive AOE, especially related to assertion and tension reduction, would be most associated with drinking to cope with social situations. Fifty-six community volunteers from a larger study on attentional bias and drinking to cope were divided into high (n=36) and low (n=20) drinking to cope groups following completion of a questionnaire battery. Findings indicated AOE were well able to classify drinking to cope status, with 91% of cases correctly classified. As hypothesized, assertion and tension reduction AOE uniquely contributed to the discriminant function in classifying drinking to cope groups. These findings have implications for the prevention and treatment of alcohol use disorders and suggest that AOE should be further investigated as potential moderators of the relationship between social anxiety and alcohol use disorders.

Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.

CONTEXT: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES: To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS: Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES: Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS: All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.

Measurement and choice of drinking outcome variables in the COMBINE Study.

OBJECTIVE: The COMBINE Study, a federally funded multisite clinical trial, endeavored to choose drinking and related outcome variables that were scientifically sound and had both convergent validity with previously published studies and face validity for clinical meaning. This article describes these variables and the methods used to collect them. METHOD: In choosing the primary outcome drinking variables, the mechanisms of action of naltrexone and acamprosate were considered along with previously published results for them and the psychosocial therapies utilized (Project MATCH). In addition, enough previous data were required to abstract meaningful power calculations for sample size estimates. Attention was paid to methodological detail in collection of drinking data, and confirmatory biological variables (carbohydrate deficient transferrin and gamma glutamyl transpeptidase) were incorporated into the study design. RESULTS: Daily standard drinks were collected by calendar-based methods with a stated goal of 90% within-treatment drinking data to be collected. "Percentage of days abstinent" and "time to first heavy drinking day" were chosen as primary outcome variables. Standardized daily alcohol consumption data can be applied to various statistical approaches, including hierarchical linear modeling and multiple relapse event analyses, which can evaluate a progression of improvement or worsening over time. CONCLUSIONS: Trained individuals using calendar-based methods attempting to collect all daily drinking data, independent of treatment dropout, should enhance interpretive validity of treatment differences. Convergence of drinking data with biological marker changes, quality of life, craving and health services utilization will enhance the overall validity of both the within-treatment and the posttreatment results for the COMBINE Study.

Animal Research: Charting the Course for FAS.

Animal models of FAS have allowed researchers to study the mechanisms behind alcohol's deleterious effects on fetal development. Such models have helped verify hypotheses based on studies of children with FAS and uncover new features of FAS not evident in humans.

A double-blind, placebo-controlled trial of sertraline in depressed adolescent alcoholics: a pilot study.

In order to preliminarily evaluate the efficacy, safety and tolerability of the serotonin reuptake inhibitor, sertraline, in the treatment of adolescents with a primary depressive disorder and a comorbid alcohol use disorder, a 12-week double-blind, placebo-controlled trial of sertraline plus cognitive behavior group therapy was conducted. Subjects were 10 outpatient treatment-seeking adolescents. Baseline assessment included the K-SADS, HAM-D, SCID, and the Time-Line Follow-Back. The HAM-D and the Time-Line Follow-Back were performed weekly thereafter. Both groups showed a significant reduction in depression scores with an average reduction between baseline and endpoint HAM-D score of -9.8 (F(1,8)=26.14, p

Alcohol tolerance and nicotine cross-tolerance in adolescent mice.

The present experiment was designed to evaluate the development of tolerance to alcohol and cross-tolerance to nicotine in adolescent mice. C57BL/6J mice (30-40 days old) were injected IP with alcohol (2.5 g/kg) for 4 consecutive days. A control group received four saline injections. On the test day, all subjects received an alcohol injection. Tolerance to alcohol's hypothermic effect was observed. Mice (male and female) exposed to alcohol for the 4 previous days showed less hypothermic response to an alcohol challenge than animals injected for 4 days with saline and then challenged with alcohol. Tolerance to alcohol's motor incoordinating effects and differences in blood alcohol concentrations were not observed. Thirty days following alcohol treatment, the same mice received a single nicotine injection (1 mg/kg) to assess cross-tolerance. Nicotine's effect on locomotor activity (open field test) and rectal temperature varied as a function of prior adolescent alcohol exposure and gender. Specifically, female mice who had been exposed to alcohol administrations were more resistant to nicotine's effect on locomotion and temperature than saline-treated animals. In summary, these data demonstrate that adolescent mice develop tolerance to some, but not all, alcohol-induced responses, and that female mice are cross-tolerant to nicotine's effects on temperature and activity.

Attentional bias and drinking to cope with social anxiety.

This study investigated the sensitivity of the emotional Stroop test for identifying individuals who reported drinking to cope with social fears. Community volunteers completed a modified Stroop task during which social threat, alcohol-related, and control words were presented. High scores on drinking-to-cope measures were hypothesized to be associated with longer response latencies to both social threat and alcohol-related words. Consistent with previous studies, alcohol dependence was correlated with latencies for alcohol-related words, and level of social anxiety was correlated with response latency to social threat words. As expected, drinking-to-cope measures predicted response latency to alcohol-related and social threat words. These results suggest that the emotional Stroop test is useful in studying the relationship between social anxiety and alcohol consumption.

Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder.

Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders.

Self-medication in social phobia: a review of the alcohol literature.

It is well documented that many individuals endorse the belief that alcohol reduces social anxiety. Individuals with social phobia, therefore, might be expected to use alcohol as a coping strategy in an attempt at self-medication. The purpose of the present paper was to review the published literature on the relationship between alcohol use and social phobia to test the self-medication hypothesis (SMH). Support for one aspect of the SMH was found; individuals with social phobia use alcohol to reduce anxiety. Support for the second premise, that alcohol actually reduces social anxiety, was less conclusive.

Confirmatory analysis of the adolescent obsessive compulsive drinking scale (A-OCDS): a measure of 'craving' and problem drinking in adolescents/young adults.

The A-OCDS was modeled after the Obsessive Compulsive Drinking Scale (OCDS) to establish an instrument appropriate for use in adolescent/young adult populations. Initial exploratory analysis of the A-OCDS revealed two factors, namely "irresistibility" and "interference," which were specific and sensitive to identifying problematic drinking. The study objective was to administer the A-OCDS to obtain data for confirmatory analyses regarding the dimensionality of the scale, its reliability and its sensitivity and specificity in identifying problem drinkers. The confirmatory factor analysis supported the two previously identified factors. Using logistic regression to predict drinking classifications, the predictive value of the subscale scores for predicting problem drinking was statistically significant (irresistibility p = 0.0001, and interference p = 0.0001). We concluded that the A-OCDS was confirmed as a scale for identifying certain dimensions of "craving" and problematic drinking in adolescents/young adults. This scale may be useful as a screening tool, as well as monitoring change over time.

Baseline Differences in Social Support Among Treatment-Seeking Alcoholics With and Without Social Phobia.

Differences on demographics and seven measures of social support between matched, treatment-seeking alcoholics with and without social phobia (SP and NSP groups, respectively) were examined. The groups did not differ on most demographic variables, although the SP group (n = 397) had a lower occupational status and had fewer years of education (both p's <.01) than the NSP group (n = 397). On social support measures, the SP group had less perceived social support from friends and had a lower performance on the social behavior role scale than the NSP group (both p's <.001). The two groups were unexpectedly more similar than different on the measures of interest in this study; however, the differences identified are meaningful for treatment planning. It is important to ascertain the quantity and sources of social support which are available to these clients in order to maximize positive treatment outcomes.

Treating individuals with social anxiety disorder and at-risk drinking: phasing in a brief alcohol intervention following paroxetine.

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N=83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83)=61.5, p<0.0001) and drinking to cope (e.g. F(4,79)=23, p<0.0001) and these two constructs correlated with each other (B=3.39, SE=0.696, t(71)=4.88, p<0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope.

Anxiety and alcohol use disorders: comorbidity and treatment considerations.

The co-occurrence of anxiety disorders and alcohol use disorders (AUDs) is relatively common and is associated with a complex clinical presentation. Sound diagnosis and treatment planning requires that clinicians have an integrated understanding of the developmental pathways and course of this comorbidity. Moreover, standard interventions for anxiety disorders or AUDs may need to be modified and combined in targeted ways to accommodate the unique needs of people who have both disorders. Optimal combination of evidence-based treatments should be based on a comparative balance that considers the advantages and disadvantages of sequential, parallel, and integrated approaches.

12-Step Therapy and Women with and without Social Phobia: A Study of the Effectiveness of 12-Step Therapy to Facilitate AA Engagement.

Alcoholism treatment often encourages involvement in Alcoholics Anonymous (AA). Little provision is made for women with social phobia (SP), who have been reported to have worse outcomes in twelve-step-facilitation (TSF) relative to cognitive behavioral therapy. This study examined whether SP moderated the effects of gender for these women in TSF. 133 SP alcoholics assigned to TSF (35 females and 98 males) in Project MATCH were compared to a non-SP control group. SP women drank earlier and more intensely than non-SP women and all males, had equivalent AA attendance and completion of Step 5, and were less likely to acquire a sponsor during TSF.