Rethinking Unhealthy Alcohol Use in the United States: A Structured Review.

Greater than moderate alcohol use spans a continuum that includes high levels of total alcohol consumed per period (heavy drinking) as well as episodes of intense drinking (binges) and can give rise to alcohol use disorder (AUD) when associated with an inability to control alcohol use despite negative consequences. Although moderate drinking and AUD have standard, operable definitions in the United States (US), a significant "gray area" remains in which an individual may exceed recommended drinking guidelines but does not meet the criteria for AUD (hereafter referred to as unhealthy alcohol use). To address this need, we conducted a structured literature search to evaluate how this gray area is defined and assess its burden within the US. For purposes of this review, we will refer to this gray area as "unhealthy alcohol use." Although numerous terms are used to describe various unsafe drinking practices, our review did not find any studies in which the specific prevalence and/or burden of unhealthy alcohol use was evaluated. That is, we found no studies that focus exclusively on individuals who exceed moderate drinking guidelines but do not meet AUD criteria. Furthermore, we did not discover an established framework for identifying individuals with unhealthy alcohol use. The lack of a consistent framework for identifying unhealthy alcohol users has significant implications for patient management and disease burden assessment. Therefore, we propose the following framework in which unhealthy alcohol use comprises 2 distinct subpopulations: those at risk of experiencing alcohol-related consequences and those who have subthreshold problems associated with use. The former, termed "risky drinkers," are defined by exceeding recommended guidelines for moderate drinking (⩽1 or 2 drinks per day for women and men, respectively). People with subthreshold problems associated with use, defined as exhibiting exactly 1 AUD symptom, would be classified as "problematic drinkers" within this proposed framework. These definitions would help bring the core elements of unhealthy alcohol use into focus, which in turn would help identify and provide management strategies sooner to those affected and reduce the overall burden of unhealthy alcohol use.

Heterogeneity of nonadherent buprenorphine patients: subgroup characteristics and outcomes.

OBJECTIVES: To examine patient characteristics and outcomes associated with nonadherence to buprenorphine and to identify specific patterns of nonadherent behavior. STUDY DESIGN: Cross-sectional, retrospective analysis of health claims data. METHODS: Aetna's administrative claims data were used to categorize incident opioid use disorder (OUD) patients based on buprenorphine medication possession ratio (MPR) into adherent (n = 172) and nonadherent (n = 305) groups. Adherent groups were then divided into 5 subgroups based on level of MPR, as well as 2 a priori-defined groups: intermittent adherent (IA) and early treatment discontinuation-no consequences (ETDNC). Groups were compared on patient characteristics and outcomes. RESULTS: Nonadherent members incurred significantly greater healthcare costs and were more likely to relapse (P <.05). The use of high-cost healthcare services increased as a function of decreasing MPR (P <.05). Assessment of the a priori groups revealed IA members to have outcomes similar to nonadherent patients, while ETDNC members exhibited outcomes similar to adherent members. CONCLUSIONS: Administrative claims can be used to define subgroups of buprenorphine-medication assisted treatment (B-MAT) patients. Nonadherence was related to an increased likelihood of relapse, and there is an inverse relationship between MPR and cost. The heterogeneity observed within this sample indicates that treatment regimens effective for 1 subgroup may not be appropriate for all OUD patients. Increased understanding of B-MAT nonadherent subgroups may facilitate development of new interventions and medications specifically designed for nonadherent B-MAT patients, potentially leading to improved outcomes and reduced costs of care.

Relationship between buprenorphine adherence and health service utilization and costs among opioid dependent patients.

Buprenorphine-medication assisted therapy (B-MAT) is an effective treatment for opioid dependence, but may be considered cost-prohibitive based on ingredient cost alone. The purpose of this study was to use medical and pharmacy claims data to estimate the healthcare service utilization and costs associated with B-MAT adherence among a sample of opioid dependent members. Members were placed into two adherence groups based on 1-year medication possession ratio (≥ 0.80 vs. <0.80). The B-MAT adherent group incurred significantly higher pharmacy charges (adjusted means; $6,156 vs. $3,581), but lower outpatient ($9,288 vs. $14,570), inpatient ($10,982 vs. $26,470), ER ($1,891 vs. $4,439), and total healthcare charges ($28,458 vs. $49,051; p<0.01) compared to non-adherent members. Adherence effects were confirmed in general linear models. Though B-MAT adherence requires increased pharmacy utilization, adherent individuals were shown to use fewer expensive health care services, resulting in overall reduced healthcare expenditure compared to non-adherent patients.

Concurrent naltrexone and prolonged exposure therapy for patients with comorbid alcohol dependence and PTSD: a randomized clinical trial.

IMPORTANCE: Alcohol dependence comorbid with posttraumatic stress disorder (PTSD) has been found to be resistant to treatment. In addition, there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use. OBJECTIVE: To compare the efficacy of an evidence-based treatment for alcohol dependence (naltrexone) plus an evidence-based treatment for PTSD (prolonged exposure therapy), their combination, and supportive counseling. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, randomized clinical trial of 165 participants with PTSD and alcohol dependence conducted at the University of Pennsylvania and the Philadelphia Veterans Administration. Participant enrollment began on February 8, 2001, and ended on June 25, 2009. Data collection was completed on August 12, 2010. INTERVENTIONS: Participants were randomly assigned to (1) prolonged exposure therapy plus naltrexone (100 mg/d), (2) prolonged exposure therapy plus pill placebo, (3) supportive counseling plus naltrexone (100 mg/d), or (4) supportive counseling plus pill placebo. Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions. All participants received supportive counseling. MAIN OUTCOMES AND MEASURES: The Timeline Follow-Back Interview and the PTSD Symptom Severity Interview were used to assess the percentage of days drinking alcohol and PTSD severity, respectively, and the Penn Alcohol Craving Scale was used to assess alcohol craving. Independent evaluations occurred prior to treatment (week 0), at posttreatment (week 24), and at 6 months after treatment discontinuation (week 52). RESULTS: Participants in all 4 treatment groups had large reductions in the percentage of days drinking (mean change, -63.9% [95% CI, -73.6% to -54.2%] for prolonged exposure therapy plus naltrexone; -63.9% [95% CI, -73.9% to -53.8%] for prolonged exposure therapy plus placebo; -69.9% [95% CI, -78.7% to -61.2%] for supportive counseling plus naltrexone; and -61.0% [95% CI, -68.9% to -53.0%] for supportive counseling plus placebo). However, those who received naltrexone had lower percentages of days drinking than those who received placebo (mean difference, 7.93%; P = .008). There was also a reduction in PTSD symptoms in all 4 groups, but the main effect of prolonged exposure therapy was not statistically significant. Six months after the end of treatment, participants in all 4 groups had increases in percentage of days drinking. However, those in the prolonged exposure therapy plus naltrexone group had the smallest increases. CONCLUSIONS AND RELEVANCE: In this study of patients with alcohol dependence and PTSD, naltrexone treatment resulted in a decrease in the percentage of days drinking. Prolonged exposure therapy was not associated with an exacerbation of alcohol use disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006489.

Opioid analgesic-treated chronic pain patients at risk for problematic use.

OBJECTIVES: To characterize potentially problematic opioid use (PPOU) among opioid analgesic-treated chronic pain (OAT-CP) patients and to compare their healthcare service utilization and expenditures with those of a control group of OAT-CP patients not exhibiting these behaviors. STUDY DESIGN: Cross-sectional, retrospective analysis of health claims data. METHODS: Members of a national health plan (n = 3891) with chronic pain and an opioid prescription were categorized into 3 groups: PPOU group (n = 1499), those displaying evidence of doctor shopping or rapid opioid dose escalation; buprenorphine/naloxone group (n =199), those who filled a prescription for buprenorphine/naloxone, which served as a proxy for opioid dependence; and control group (n = 2193), those not meeting either of the above criteria. Groups were compared on 1-year healthcare service utilization and costs. RESULTS: The PPOU group made up more than one-third of the study sample. Compared with the control group, they incurred significantly greater 1-year adjusted mean pharmacy costs ($6573 vs $6160), office costs ($5705 vs $4479), emergency department (ED) costs ($835 vs $388), inpatient costs ($15,646 vs $7445), and total healthcare costs ($39,048 vs $26,171) (all P <.05). The buprenorphine/naloxone group incurred significantly greater 1-year pharmacy costs ($6981 vs $6160) and ED costs ($1126 vs $388) (both P <.05) than the control group. CONCLUSIONS: The PPOU group had the highest healthcare service utilization and costs. Although drivers of elevated service utilization and cost among this population are not clear, health plans may want to focus on PPOU case identification and development of interventions.

A nonopioid procedure for outpatient opioid detoxification.

OBJECTIVES: (1) To describe a new protocol using nonopioid medications (clonidine, lorazepam, trazodone, and a stimulant) to successfully complete outpatient opioid detoxification, (2) to determine clinical and demographic characteristics of patients who successfully complete an outpatient opioid detoxification, and (3) to determine the safety and clinical utility of the use of this combination of medications in the treatment of opioid withdrawal. METHODS: In a posthoc evaluation study in a New York State-licensed outpatient detoxification unit of a substance abuse treatment facility, 223 heroin-dependent adults presenting for treatment were provided outpatient opioid detoxification. In the course of the opioid detoxification protocol of the facility, patients received clonidine, lorazepam, trazodone, and either a stimulant (methylphenidate or modafinil) or no stimulant, in combination on a daily basis. At each daily visit, signs and symptoms were assessed, and medications and dosing instructions were given for the following 24 hours. On completion of the detoxification protocol, patients were induced with oral naltrexone. RESULTS: Overall, 61.0% (136) of the patients in this study successfully completed the outpatient detoxification protocol and were induced with naltrexone. Pretreatment demographic variables that predicted successful treatment included full-time employment, family support, private medical insurance, and referral by an employee assistance program. About 77% of patients with good prognosis successfully completed outpatient detoxification treatment. The addition of a stimulant improved patient retention and reduced the incidence of hypotension. CONCLUSIONS: The outpatient detoxification of opioid-dependent patients without the use of opioids has traditionally led to such high drop out rates that most clinical programs do not even consider the option. This makes it difficult to induce patients with opioid antagonists such as oral naltrexone or sustained release naltrexone. We describe a protocol here that leads to excellent rates of successful detoxification. This nonopioid detoxification methodology permits induction of naltrexone without the delay experienced in opioid-based titrations, and it thus facilitates the use of opioid antagonists for sustained abstinence, enhanced aftercare treatment outcomes, and opioid-free recovery.

Combined effects of alcohol and hepatitis C: a secondary analysis of alcohol use biomarkers and high-risk behaviors from two medication trials for alcohol dependence.

OBJECTIVES: The goal of this secondary analysis was to examine the combined effects of HCV infection and recent alcohol use on baseline biologic markers of alcohol consumption in two outpatient medication trials for alcohol dependence. In addition, the relationship between Hepatitis C virus (HCV) infection and behavioral risk factors for HCV infection in these clinical populations were examined. METHODS: Data (n=345) from two randomized, placebo-controlled trials of naltrexone and psychosocial treatment for alcohol dependence (Study I, n=212) and comorbid alcohol and cocaine dependence (Study II, n=133) were used to examine baseline measures of HCV risk behaviors (injection drug use, needle sharing), and biomarkers of alcohol use (AST, ALT, GGT and CDT) were compared by HCV serostatus first within each study and then across studies. RESULTS: Although groups had differing sociodemographic profiles (as indicated by race, marital status, level of education) subjects in Study I exhibited no statistically significant differences from the Study II cohort in HCV prevalence (12.7 vs. 20.0%, p=0.07), lifetime history of injection drug use (13.8 vs. 22.0%, p=0.74), lifetime history of needle sharing (9.1 vs. 18.0%, p=0.62). As such, the data from both studies were analyzed together. Regardless of drinking status, HCV infection was significantly associated with an upward shift in the baseline level of ALT, AST, and GGT (p<0.006 for all measures) and a downward shift in baseline CDT (p=0.002). When using standard laboratory cutoff values to determine clinically significant elevations, HCV seropositivity was significantly associated with elevations in ALT, AST, GGT (p<0.001), and with decreases in CDT (p=.002). CONCLUSIONS: These data emphasize the importance of evaluating HCV infection and HCV risk behaviors at intake in medication trials for alcohol dependence and also raise questions regarding the use of cutoff scores for ALT, AST, GGT and CDT levels as biologic markers of alcohol use in subjects when HCV status is unknown.

Alcohol-induced disinhibition expectancies and impaired control as prospective predictors of problem drinking in undergraduates.

Trait disinhibition is associated with problem drinking and alcohol drinking can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale (Leeman, Toll, & Volpicelli, 2007) and the Impaired Control Scale (Heather et al., 1993) predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, Dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 Euphoric/social Disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively, and that these phenomena should be targeted in early intervention efforts.

A placebo-controlled randomized clinical trial of naltrexone in the context of different levels of psychosocial intervention.

BACKGROUND: Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content. METHODS: Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone (100 mg/d). Subjects were also randomly assigned to 1 of 3 psychosocial interventions. All patients were assessed for alcohol use, medication adherence, and adverse events at regularly scheduled research visits. RESULTS: There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome. CONCLUSIONS: Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response.

The Drinking-Induced Disinhibition Scale (DIDS): a measure of three types of disinhibiting effects.

Links between trait disinhibition and high-risk drinking are well established. It is also known that alcohol has disinhibiting effects. Nonetheless, there is no measure in the literature devoted exclusively to assessing disinhibiting effects of alcohol. The multidimensional Drinking-Induced Disinhibition Scale (DIDS) was developed as part of Study I, a prospective survey conducted with undergraduates (N=337). Study II, a cross-sectional survey (N=260), allowed for a confirmatory factor analysis and further validation of the measure through comparisons with an expectancies scale. The nine-item DIDS is comprised of three subscales assessing euphoric/social, dysphoric and sexual disinhibition. All three subscales had good internal consistency and adequate test-retest reliability. Convergent and discriminant validity were established in both studies. The subscales had different associations with high-risk drinking: sexual disinhibition predicted heavy episodic drinking; dysphoric disinhibition predicted alcohol-related problems and euphoric/social had associations with both. A cluster analysis revealed four distinct disinhibition profiles (i.e., low effect drinker; high euphoric/social only; high euphoric social and dysphoric; high euphoric/social and sexual), which predicted likelihood of high-risk drinking.

Impaired control and undergraduate problem drinking.

AIMS: Impaired control, one of the hallmarks of addiction, is also one of the earliest dependence symptoms to develop. Thus impaired control is particularly relevant to undergraduates and other young adults with relatively brief drinking histories. The main goal of this study was to determine whether impaired control predicted heavy episodic drinking and alcohol-related problems cross-sectionally in an undergraduate sample after controlling for gender, family history of alcohol and drug problems, and several other established predictor variables from the undergraduate alcohol literature. METHODS: A sample of first-year undergraduates (n=312) completed Part 2 of the Impaired Control Scale (ICS) and other measures related to alcohol use as part of a larger study on problem drinking in undergraduates. RESULTS: Scores on Part 2 of the ICS predicted heavy episodic drinking and alcohol-related problems cross-sectionally even after controlling for all other predictor variables. Notably, impaired control was a stronger predictor of alcohol-related problems than overall weekly alcohol consumption. Part 2 of the ICS was found to be a reliable and valid measure for use with undergraduates. CONCLUSIONS: These findings support the notion that impaired control is one of the earliest dependence symptoms to develop. The ICS is an effective tool for identifying young adults at risk for problem drinking.

The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders.

While the U.S. Food and Drug Administration has approved several medications for the treatment of alcohol-related problems, their use has not gained wide acceptance in the United States. Typically, patients with alcohol use disorders are only referred to psychosocial support (e.g., Alcoholics Anonymous). However, the use of pharmacotherapy may complement psychosocial treatments, as evidence shows that pharmacotherapy can improve treatment outcomes. The effectiveness of pharmacotherapy depends on patient compliance with taking the medication and the context in which the medication is administered. BRENDA is a psychosocial program designed specifically to be used by many types of healthcare providers, including primary care clinicians. Designed to enhance medication and treatment compliance, BRENDA is an ideal approach for use in conjunction with pharmacotherapy. The BRENDA approach has 6 components: 1) a biopsychosocial evaluation; 2) a report of findings from the evaluation given to the patient; 3) empathy; 4) addressing patient needs; 5) providing direct advice; and 6) assessing patient reaction to advice and adjusting the treatment plan as needed. This paper describes these components and discusses how the empirical support for each component is linked to the enhancement of medication compliance and the improvement of treatment outcomes.

Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol.

This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity.

Demographic and social adjustment characteristics of patients with comorbid posttraumatic stress disorder and alcohol dependence: potential pitfalls to PTSD treatment.

The present study examined the demographic and social adjustment characteristics of a sample seeking treatment for comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). Using descriptive statistics, we compared the characteristics of this group to those of a sample seeking treatment for PTSD alone and to another sample seeking treatment for AD alone. Results indicated that compared to the PTSD alone and AD alone samples, a greater percentage of the comorbid sample was unemployed, with low income and living without the support of a spouse or intimate partner. Further, participants in the comorbid sample were less likely than those in the PTSD alone sample to have received more than a high school education, though the comorbid and AD samples were comparable on education level. These results are discussed with attention to how poor social adjustment may place comorbid AD-PTSD patients at greater risk for premature termination of therapy, particularly when that treatment is focused on alleviating PTSD symptoms. Suggestions are made to enhance retention of these difficult patients in treatment programs.

Patient attitudes toward treatment predict attendance in clinical pharmacotherapy trials of alcohol and drug treatment.

This study evaluated for 152 patients the relationship between their attitudes toward treatment and session attendance in pharmacotherapy research trials aimed at treating alcohol dependence. The study included a new, 50-item, patient-administered measure of attitudes, Treatment Research Experiences and Attitudes Task (TREAT), which is comprised of ten items from each of five attitudinal dimensions typically associated with treatment adherence: treatment setting, taking medication, social support, medical professional, and intrinsic patient factors. Patients attending 80% or more clinical sessions scored higher, i.e., were more favorable on four of five of attitudinal dimensions. Thus, patient attitudes toward treatment may be useful in identifying areas that limit or improve treatment attendance.

A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients.

This study examined the association between two specific polymorphisms of the gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A(+118)G (Asn40Asp) and C(+17)T (Ala6Val) SNPs in the gene encoding the mu-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p=0.044) and a longer time to return to heavy drinking (p=0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p=0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a mu-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

Alcoholism treatment adherence: older age predicts better adherence and drinking outcomes.

OBJECTIVE: Adherence to treatment has been demonstrated to be an important factor for remission from alcohol dependence. The authors compared therapy and medication adherence for treatment of alcohol dependence in older adults with adherence in younger adults. METHODS: All subjects were participants in a randomized, double-blind, placebo-controlled efficacy trial of naltrexone for the treatment of alcohol dependence. All subjects received a medically-based psychosocial intervention focused on motivating patients to change and on adherence to treatment. The therapy is nonconfrontational and is delivered by a nurse-practitioner. RESULTS: Compared with younger adults, older adults had greater attendance at therapy sessions and greater adherence to the medication. Age-group was the only pretreatment factor associated with adherence. The greater adherence in older adults translated to less relapse than in younger adults. CONCLUSION: Treatment for alcohol dependence can be effective for older adults. Older adults appear to respond well to a medically-oriented program that is supportive and individualized. In fact, findings from this study suggest that older adults can be treated in mixed-age treatment settings when psychotherapeutic strategies are used that are age-appropriate and delivered on an individual basis.

Carbohydrate-deficient transferrin levels reflect heavy drinking in alcohol-dependent women seeking treatment.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is a biochemical marker that has been shown to be sensitive in detecting heavy drinking in men, but studies examining CDT in women have been inconsistent because of small sample sizes and failure to consider hormonal status. In healthy female subjects, CDT levels are significantly higher in premenopausal women with higher estradiol (E2) levels (>30 pg/ml) and those taking exogenous estrogens (oral contraceptives, hormone replacement therapy) compared with men and postmenopausal women. This study examined the relationship between drinking behavior and CDT levels in a large sample of alcohol-dependent women and contrasted findings in a comparison group of alcohol-dependent men. The study also examined the extent that E2 levels mediated the relationship between CDT levels and heavy drinking in the alcohol-dependent women. METHODS: This study examined the association between CDT level at treatment entry and alcohol consumption the month before initiating treatment in 96 women with a DSM-III-R diagnosis of alcohol dependence, as compared with similar data in 123 male alcoholics. To explore the relationship between E2 and CDT, E2 was measured in women at the time of CDT sampling. Linear regression was used to examine whether patterns of alcohol consumption in the 28 days before the CDT blood sampling predicted the CDT level in women and men presenting for treatment for alcohol dependence. RESULTS: CDT levels were higher in women than men and were related to quantitative alcohol consumption (total standard drinks, percentage of days drinking, percentage of days of heavy drinking) in the month before initiating treatment, irrespective of E2 levels in women. CONCLUSIONS: These results suggest that in a larger sample of female alcoholics, the amount of alcohol consumed predicted CDT, similar to what has been reported in male alcoholics. The E2 status did not seem to mediate these results.

Concurrent cocaine withdrawal alters alcohol withdrawal symptoms.

This study compares alcohol withdrawal severity during outpatient detoxification in alcohol dependent subjects (ALC) and in subjects dependent on both alcohol and cocaine (ALC/COC). Subjects included 123 ALC and 66 ALC/COC subjects. Baseline demographic and drug use variables, alcohol withdrawal symptoms, and the total amount of oxazepam taken during alcohol detoxification were compared between the two groups. Compared to ALC subjects, ALC/COC subjects were younger, more likely to be African-American, and had less severe histories of alcohol dependence. However, alcohol withdrawal symptom severity did not differ significantly between the two groups. Nevertheless, controlling for differences in alcohol use history, ALC/COC subjects still received less oxazepam than did ALC subjects to treat alcohol withdrawal symptoms. Despite similar intensity of alcohol withdrawal symptoms, ALC/COC subjects received less oxazepam to treat alcohol withdrawal symptoms compared to ALC subjects. Both subject and clinician factors may explain the difference in oxazepam use.

A comparison of the effects of 6-beta naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats.

We recently reported that 6-beta naltrexol, the major metabolite of naltrexone in humans, reduced ethanol consumption in rats. Two new experiments were designed to compare 6-beta naltrexol and naltrexone across three dose levels on an ethanol or sucrose baseline using a limited-access procedure in Wistar rats. The results of Experiment 1 showed that both 6-beta naltrexol and naltrexone reduced ethanol consumption across a range of doses. An in vivo assay showed that naltrexone was approximately 25 times more potent than 6-beta naltrexol at comparable ED50 doses. In addition, there was no indication of systematic development of tolerance to the effect of either drug across the 4 days of drug administration. In Experiment 2, both 6-beta naltrexol and naltrexone reduced the consumption of a sucrose solution using a limited-access procedure. The implications of these data for the development of pharmacotherapeutic agents capable of reducing drinking in recovering alcoholics are discussed.