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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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Percy Menzies has no active conflict of interest to disclose. He previously consulted for Alkermes. Joseph R. Volpicelli is a paid consultant for Orexo and Imbrium Therapeutics., (© The Author(s) 2022.)

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.

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.

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.

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., (Copyright 2009 APA)

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.

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.

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.

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.

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.

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.

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.

Objective: The purpose of this investigation was to examine the utility of thee craving instruments to predict drinking during treatment. The three assessments used were the Penn Alcohol Craving Scale (PACS), the Alcohol Urge Questionnaire (AUQ) and Items 1-6 of the Obsessive subscale (OBS) of the Obsessive Compulsive Drinking Scale (OCDS)., Method: The three instruments were administered during the course of a 9-month, double-blind, placebo-controlled trial of 100 mg/day of naltrexone, and a manual-based psychosocial intervention using the BRENDA manual conducted at the University of Pennsylvania's Treatment Research Center. Participants (133 men and 50 women at the initiation of the study) used these instruments to self-report craving on a weekly or biweekly basis. The weekly number of drinks was reported using the Timeline Followback interview. The data were analyzed with generalized estimating equations using craving scores at 1 week as the independent variable and number of drinks in the subsequent treatment week as the dependent variable., Results: Each of the three scales predicted drinking during the subsequent treatment week. The PACS was the strongest predictor followed closely by the OBS and then the AUQ. Most important, craving as measured by the three scales was a stronger predictor of subsequent drinking than was drinking during the prior treatment week., Conclusions: Craving assessment provides a useful means of predicting drinking during treatment. Such information would be helpful in designing clinical trials and for many treatment modalities.

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.

Comorbid abuse of and dependency on multiple drugs is a common occurrence clinically. We have developed an animal model that provides rats with the opportunity to choose, through oral consumption, between concurrently available ethanol and cocaine with water also available. This provides the ability to screen for the effectiveness of potential pharmacotherapeutic agents on the baseline consumption of both drugs. We used this animal model to evaluate the effects of naltrexone, at doses of 0, 1.0, 3.0, and 10.0 mg/kg, on concurrent oral consumption of ethanol and cocaine solutions. Naltrexone at all doses significantly reduced both consumption of and preference for ethanol. Consumption of both cocaine and water was unaffected by naltrexone, supporting the suggestion that the effects of naltrexone were selective for ethanol. These findings support the suggestion that ethanol and cocaine act on different central reward pathways. The implications of these findings for the clinical use of naltrexone in populations with comorbid ethanol and cocaine abuse are discussed.

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.

Both cocaine withdrawal symptoms, measured by an instrument called the Cocaine Selective Severity Assessment (CSSA), and urine toxicology results obtained at the start of treatment have been shown to predict treatment outcome in outpatient cocaine dependence treatment. This study further evaluates the predictive validity of the CSSA and urine toxicology results, alone and in combination. Subjects included 76 cocaine-dependent individuals who participated in 7-week, outpatient, pilot medication trials for cocaine dependence. Predictor variables included CSSA scores and results from a urine toxicology screen obtained on the first day of medication treatment. Successful outcome was defined as 3 continuous weeks of self-reported abstinence from cocaine confirmed by urine toxicology screens. Predictive validity was assessed by logistic regression analysis. Both the urine toxicology screen and the CSSA scores were significant predictors of 3 weeks of continuous abstinence from cocaine, and the inclusion of both variables significantly improved the predictive validity of either variable alone. Urine toxicology results and CSSA scores obtained at treatment entry are useful predictors of outcome in outpatient cocaine dependence treatment.

Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.

Naltrexone has repeatedly been shown to reduce drinking in alcohol-dependent patients. Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment. In addition, laboratory studies suggest that naltrexone may be more efficacious among patients with a high familial loading of alcohol problems. We explored both of these possibilities in the context of the first 12-week phase of a double blind, placebo-controlled naltrexone trial. A total of 121 patients were randomized to receive 100 mg/day naltrexone and 62 patients were randomized to receive placebo. Both naltrexone and placebo were given in conjunction with a psychosocial intervention designed to be integrated with the use of pharmacotherapy. This intervention was administered by nurse practitioners. Overall, patients randomized to naltrexone reported drinking five or more drinks on fewer days than did placebo controls (p = .04). Interactions were observed between medication group assignment and both craving level prior to randomization (p = .02) and family loading of alcohol problems (p = .05). In both cases, the interaction was in the predicted direction. These data suggest that patients with high levels of alcohol craving or a strong family history of alcoholism are more likely to benefit from naltrexone treatment.

Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.

This study evaluated the ability of cocaine withdrawal symptoms, measured by the Cocaine Selective Severity Assessment (CSSA) and initial urine toxicology results, to predict treatment attrition among 128 cocaine dependent veterans participating in a 4-week day hospital treatment program. The CSSA was administered and a urine toxicology screen was obtained at intake and at the start of the day hospital (about 1 week later). The combination of a positive urine toxicology screen and a high CSSA score at intake predicted failure to complete treatment. Urine toxicology results at the start of the day hospital, but not at intake, predicted failure to complete treatment. Among participants without other psychiatric illness, high CSSA scores at intake predicted failure to complete treatment. The presence of cocaine withdrawal symptoms and a positive urine toxicology screen are clinically useful predictors of treatment attrition.

It has frequently been reported that a high percentage of individuals, identified as either alcohol- or cocaine-dependent, concurrently abuse both drugs. The experiments reported here represent a continuing effort to develop an animal model to predict the effects of a potential pharmacotherapeutic agent on concurrently available oral ethanol and cocaine. These experiments utilized drinkometer circuitry to assess the effects of gamma-vinyl-GABA (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, on the consumption and temporal pattern of responses for orally self-administered ethanol and cocaine. The results of these experiments showed that GVG, at doses of 100, 200 and 300 mg/kg, reduced both ethanol and cocaine consumption in a dose-related manner. When compared to vehicle, GVG at all doses significantly reduced ethanol consumption while consumption of cocaine was significantly reduced only at 300 mg/kg. This is consistent with data showing that GVG reduces consumption of these drugs when administered alone and data showing that GVG is more potent in reducing ethanol-induced compared to cocaine-induced extracellular dopamine in the nucleus accumbens. Analysis of the temporal pattern of drinking across the session suggests that GVG's effects are due to a disruption of the reinforcing properties of ethanol and cocaine rather than a more general reduction in motor behavior. These data suggest that GVG has potential for clinical use in populations that abuse either alcohol or cocaine alone or in combination.

Both acamprosate and naltrexone have demonstrated clinical utility in reducing relapse to alcohol use in recovering alcoholics. The present experiments examined the effects of acamprosate and naltrexone, either alone or in combination, on basal ethanol consumption in a limited-access model with the use of outbred Wistar rats. Naltrexone, 0.1 mg/kg, significantly reduced ethanol consumption as previously reported. Acamprosate, 50 mg/kg, did not significantly reduce ethanol consumption when administered alone and provided no evidence of additive or synergistic effects when combined with naltrexone. Acamprosate, 200 mg/kg, produced a modest reduction in ethanol consumption when administered alone but no evidence of additive or synergistic effects when combined with naltrexone. From these findings, it is suggested that a combination approach of these drugs may not be any more effective than monotherapy.

Alcoholism and alcohol abuse rank among the top 3 psychiatric disorders in the United States. These disorders are associated with significant medical and economic consequences. Furthermore, studies consistently show that an investment in addiction treatment leads to overall cost savings for society. Recent work has identified specific effects of alcohol on several neurotransmitter systems, including gamma-aminobutyric acid, serotonin, dopamine, and the opioid receptors. These findings suggest that multiple pharmacologic interventions may be useful for the treatment of alcohol addiction. This article reviews the clinical use of naltrexone and discusses psychosocial programs to enhance treatment retention and adherence.

Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not be transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence.

Objective: The study examined the effectiveness of amantadine in reducing cocaine withdrawal symptoms and improving treatment outcome among cocaine-dependent patients in outpatient treatment., Method: Sixty-one cocaine-dependent subjects participated in a double-blind, placebo-controlled trial of amantadine., Results: Among subjects with severe cocaine withdrawal symptoms at the start of treatment, those who received amantadine used significantly less cocaine during the trial than did subjects who received placebo. Compared to subjects who received placebo, subjects who received amantadine submitted significantly more benzoylecgonine-negative urine samples and used cocaine on significantly fewer days during the trial., Conclusions: Amantadine may be an effective treatment for cocaine-dependent patients with severe cocaine withdrawal symptoms.

Background: In humans, 6-beta-naltrexol is the major metabolite of naltrexone, and its effectiveness at suppressing alcohol consumption in any species has not been previously investigated. Naltrexone is an opiate antagonist that reduces excessive drinking in many species, including humans with alcohol dependence. Whether 6-beta-naltrexol is an active metabolite that contributes to the efficacy of naltrexone remains unknown., Methods: Placebo and four doses of 6-beta-naltrexol were given by intraperitoneal injection to outbred Wistar rats and alcohol consumption was measured using a limited access model., Results: 6-beta-Naltrexol reduced alcohol consumption in a dose-dependent manner. At doses 7.5, 12.5, and 25 mg/kg, 6-beta-naltrexol significantly decreased consumption of a 6% ethanol solution compared with saline control groups., Conclusions: These data suggest that there may be a potential clinical use for 6-beta-naltrexol in recovering alcoholics.

Several studies have demonstrated that non-selective opioid receptor antagonists effectively reduce alcohol consumption in both animal models and at the clinical level. However, research examining the contribution of specific opioid receptor subtypes to this effect has yielded conflicting results. Some of these studies have shown that the effect is contingent upon the action of mu receptors while others have suggested that delta receptors are primarily responsible. The data reported here re-examine this question using the alcohol-preferring C57BL/6 mice. The results of this experiment demonstrate that D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP), a mu-selective antagonist, and naltrindole, a delta-selective antagonist, are equally effective at reducing alcohol consumption in a limited access model compared to a saline control group. While there was no specific comparison of the effects of these drugs on alternative appetitive behavior, neither of these drugs had effects on measured off-session food or water consumption. The results of this experiment suggest that alcohol consumption is mediated by both mu- and delta-opioid receptor subtypes.

Background: Characteristic behaviors of some alcohol-dependent individuals, e.g., binge drinking, comorbid psychopathology, and some types of alcohol-related problems, have been linked to abnormalities in serotonergic neurotransmission. However, studies that have evaluated serotonergic pharmacotherapy for reducing drinking have yielded conflicting results. One explanation for these findings is a general failure to distinguish alcohol subgroups that may be differentiated on the basis of serotonergic abnormalities. However, in 1996, Kranzler and colleagues reported that Type B alcoholics, who are characterized by high levels of premorbid vulnerability, alcohol dependence severity, and comorbid psychopathology, showed less favorable drinking outcomes in response to treatment with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This medication effect was not seen in Type A alcoholics, i.e., those with lower risk/severity of alcoholism and psychopathology. The aim of the present study was to explore the validity of differential responding by alcohol-dependent subtypes using the serotonin reuptake inhibitor, sertraline., Methods: A k-means clustering procedure was applied to a sample of alcohol-dependent subjects enrolled in a 14-week, placebo-controlled trial of 200 mg/day of sertraline, classifying them into lower-risk/severity (Type A: n = 55) and higher-risk/severity (Type B: n = 45) subgroups., Results: A significant interaction between alcoholic subtype and medication condition was found, confirming the findings of Kranzler and colleagues that alcoholic subtypes responded differentially to serotonergic medication. Somewhat at variance with their results, however, the present study showed that the lower risk/severity (Type A) subjects had more favorable outcomes when treated with sertraline compared to placebo., Conclusions: Alcoholic subtypes differentially responded to sertraline when used as a treatment to reduce alcohol drinking, with one subtype having more favorable outcomes. Subtyping alcoholics may help to resolve conflicting findings in the literature on serotonergic treatment of alcohol dependence.

We examined differences in clinical presentation for outpatient alcohol treatment in: 1) males and females, considering comorbidity; and 2) three comorbid groups, considering gender. Drinking indices and emotional, physical, and sexual abuse reports were compared in 127 male and 69 female alcohol-dependent patients who have a current (36.2%) or lifetime (20.4%) psychiatric disorder or who never had a psychiatric disorder (43.4%). Females reported more emotional and physical abuse than males. Females reported drinking smaller volumes of alcohol but on more days than males. All with current comorbidity, irrespective of gender, reported more days of heavy drinking than other groups. When evaluating drinking status, gender and comorbidity should be considered.

The effectiveness of naltrexone, a FDA-approved medication for alcohol dependence, can be improved if we support and help patients to consistently take their medication. We illustrate how patient noncompliance with treatment negatively affects outcome, and, we describe a new intervention to enhance medication compliance. Outcome was evaluated for 196 alcohol dependent outpatients who were treated with 50 mg/day naltrexone or placebo for 12 weeks. For patients who adhered to the prescribed treatment, relapse rates were lower with naltrexone than placebo (10% vs. 38.6%, p < 0.001). For noncompliant patients, relapse rates were high and comparable between naltrexone- and placebo-treated patients (42.9% vs. 40%). In a second study of 100 alcohol dependent outpatients, we introduced an intervention that resulted in better medication compliance rates compared to a previous naltrexone study of patients who did not receive the intervention (77.0% vs. 60.8%, p < 0.01). This provided some support for the use of an intervention that targets medication compliance when prescribing naltrexone.

Eighty-four cocaine-dependent mothers were randomly assigned either to a case management-oriented outpatient treatment program (CM), or to a psychosocially enhanced treatment program (PET). Both programs included onsite child care and both offered daily group therapy sessions. Subjects randomized to the PET condition were offered a variety of additional onsite services designed to meet their special psychosocial needs including parenting skills class, access to a psychiatrist, individual therapy sessions, and GED class. Patients in the CM program could gain access to these services only through referrals to community resources. Program retention was significantly better for patients in the PET condition. In addition, while the mean number of days of cocaine use decreased from baseline in both groups, the PET group had significantly fewer days of cocaine use at 12-month follow-up than the CM group. These results show that providing psychosocial enhancement services onsite can improve treatment outcome for cocaine-dependent mothers.

The present studies assessed the effects of both systemic and intraaccumbens injections of 1-aminocyclopropanecarboxylic acid (ACPC), and NMDA partial agonist, on ethanol consumption in a limited access procedure in Wistar rats. Systemically administered ACPC reduced ethanol consumption in a dose-dependent manner, while a single dose of ACPC administered bilaterally into the nucleus accumbens also reversibly reduced ethanol consumption. Indirect measures of general appetitive behavior showed no effect of ACPC on weight or water intake, which suggests that this effect of ACPC may be specific to ethanol. These data are compatible with the role of NMDA receptors in modulating ethanol consumption and provide the first data showing that ACPC can reduce ethanol consumption. ACPC has neuroprotective effects and does not show the psychotomimetic effects observed with NMDA receptor agents. Thus, ACPC may be helpful in future clinical studies designed to reduce alcohol use.

Background: This study introduces the Penn Alcohol Craving Scale (PACS), which has been used in several clinical trials at the University of Pennsylvania's Treatment Research Center. The PACS is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6., Methods: To examine the questionnaire's psychometric properties, we sampled responses from 147 individuals participating in a 9-month combined natrexone (100 mg/day)/psychotherapy trial. The psychotherapy consisted of weekly sessions of nurse-administered medication compliance and supportive treatment., Results: The PACS proved to have excellent internal consistency. Predictive validity was demonstrated via a logistic regression analysis of craving during the 2nd week of the study on alcohol relapse during weeks 3-12 of the trial. Construct validity of the PACS was demonstrated via its convergence with two commonly used measures for assessing craving, the Obsessive Compulsive Drinking Scale and the Alcohol Urge Questionnaire. Lack of correlation between PACS scores and several other noncraving, self-report measures indicates that the PACS also had good discriminant validity. Additional analyses revealed that there were significant differences in craving scores during the initial 3 weeks of the trial among those who did and those who did not relapse during weeks 3-12., Conclusion: The PACS is a reliable and valid measure of alcohol craving and can predict which individuals are at risk for subsequent relapse.

Concurrent dependence on cocaine and alcohol is common among patients seeking addiction treatment. This study was undertaken to explore the effectiveness of naltrexone (150 mg) as a potential treatment for patients who are alcohol and cocaine dependent. Of 15 subjects enrolled in the 12-week, open medication trial, 7 subjects did not complete the study. Relapse to clinically significant drinking occurred in 7 subjects (47%). There was a reduction in the average daily amount of alcohol consumed from pretreatment to treatment (p < .001) and the percentage of days engaged in drinking behavior (p < .001). Similarly, there was a reduction in the average weekly amount spent on cocaine from pretreatment to treatment (p = .001) and the percentage of days using cocaine (p < .001). This preliminary study suggests that naltrexone (150 mg) may be tolerable in patients dependent upon alcohol and cocaine and may be effective in reducing both cocaine and alcohol use. The results of this study provide a rationale for a double-blind placebo-controlled study of the efficacy of naltrexone in this difficult to treat but prevalent population.

This paper describes a rapid and systematic method of using open trials to identify medications that may be useful for the treatment of cocaine dependence. Results of these open trials can be used to prioritize medications for inclusion in subsequent double-blind, placebo-controlled trials. Preliminary results are presented from the evaluation of propranolol, nefazodone, and the combination of phentermine and fenfluramine (phen/fen). Each medication was evaluated in an open trial, and results were compared to results obtained from a group that received a multivitamin. Outcome measures included treatment retention, urine toxicology screens, self-reported cocaine use, and changes on the Addiction Severity Index (ASI). Treatment retention was significantly better in the propranolol group than in the multivitamin group. Concurrent alcohol abuse was associated with increased rates of attrition in the multivitamin group, and the phen/fen group, but not in the propranolol group. Neither the nefazodone nor the phen/fen groups showed any outcome advantages over the multivitamin group. We conclude that propranolol may enhance retention among cocaine-dependent patients, especially among those who also abuse alcohol. These results encourage a double-blind, placebo-controlled trial of propranolol.

The present study examined the effects of naltrexone, 1.0 mg/kg, administered repeatedly across both 30 and 60 days on the consumption of an unsweetened ethanol solution by outbred Wistar rats in a limited access procedure. Naltrexone significantly suppressed consumption of ethanol across both 30 and 60 days. These results provide no evidence for the development of tolerance based on such factors as receptor upregulation or supersensitivity due to the repeated administration of naltrexone across extended periods. Ethanol consumption during the final one-third of the naltrexone sessions, for both the 30- and 60-day groups, was significantly lower than during the initial sessions. These results suggest an associative component. That is, the rats apparently learned that ethanol consumption was no longer reinforcing across repeated exposures. After termination of naltrexone treatment, consumption of ethanol immediately increased. However, consumption in those rats who were administered naltrexone for 60 days remained significantly suppressed, compared with consumption in those rats who were administered naltrexone for 30 days. These results suggest that naltrexone reduces ethanol consumption by blocking endogenous opioid receptors that mediate, at least in part, ethanol's reinforcing properties. In addition, these data suggest that longer clinical use of naltrexone, as a pharmacological adjunct to psychosocial treatment for alcohol-dependent patients, may be beneficial in reducing the number of relapses experienced.

This article assesses the reliability and validity of the Cocaine Selective Severity Assessment (CSSA), a measure of cocaine abstinence signs and symptoms. Interrater reliability and scale internal consistency were high. Initial CSSA scores were significantly higher in cocaine-dependent subjects than in alcohol-dependent subjects. Initial CSSA scores were highly correlated with recent cocaine use and with severity measures from the Addiction Severity Index (ASI) including the interviewer severity rating and composite score in the drug section. Among cocaine-dependent subjects, initial CSSA scores were higher for those who failed to achieve abstinence or who subsequently dropped out of treatment. Further, CSSA scores showed consistent and marked declines over time for subjects who continued in treatment and remained abstinent. The CSSA appears to be a reliable and valid measure of cocaine abstinence symptoms and a useful predictor of negative outcomes in cocaine dependence treatment.

The effects of the universal opioid antagonist naltrexone were compared to the delta-selective opioid antagonist naltrindole and the mu-selective opioid antagonist beta-funaltrexamine on ethanol consumption in the absence of food or fluid deprivation using a limited access procedure in Wistar rats. Both naltrexone, at doses of 0.1, 0.25, 0.5, 1.0, 3.0, and 10 mg/kg, and beta-funaltrexamine, at doses of 5.0 and 20.0 mg/kg, significantly decreased consumption of a 6% ethanol solution compared to saline control groups. Naltrindole, at doses of 5.0 and 15.0 mg/kg, failed to significantly reduce ethanol consumption. In addition, the highest doses of naltrexone, which antagonize delta as well as mu-opioid receptors, did not differ significantly from the lowest doses in their ability to reduce ethanol consumption. These data suggest that ethanol consumption using the limited access paradigm in the outbred rat is modulated by mu rather than delta-opioid receptors. Although this is not consistent with other data showing that delta antagonists decrease ethanol consumption, it is suggested that these difference may be related to the alcohol-preferring rats used in those experiments.

The influence of a low dose of morphine was investigated on the acquisition and maintenance of consumption of a sweetened ethanol solution with water as the alternative in a two-bottle choice procedure. During acquisition in Experiment 1, morphine failed to significantly increase the consumption of a sweetened ethanol solution compared to either a postinjection period in the same animals or a no-treatment control group. Although morphine significantly increased sweetened ethanol consumption when compared to a saline control group, this appears to be due to a stress response to the injections, which suppressed ethanol consumption in the saline animals. During maintenance in Experiment 2, morphine significantly increased consumption of sweetened ethanol in all groups compared to consumption following saline control injections. There was no difference in this effect among the three groups, suggesting that prior history with morphine was not a factor. In addition, rats that were exposed to morphine during both experiments drank significantly more sweetened ethanol following injections in Experiment 2 than in Experiment 1. This suggests that morphine's potentiation of ethanol consumption is due to its interaction with endogenous opioid receptors that modulate the reward value of ethanol rather than more general mechanisms affecting satiety or taste. The results of these experiments provide support for both the Deficit and Surfeit Hypotheses of ethanol consumption, both of which suggest that endogenous opioid receptors are responsible, in part, for ethanol's reinforcing properties.

Background: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance., Methods: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n = 48) or matching placebo (n = 49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week)., Results: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication., Conclusions: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance.

When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been recently approved by the Food and Drug Administration for the treatment of alcohol dependence. An important clinical issue with naltrexone treatment is predicting patient compliance, which may be influenced by adverse side effects experienced during the medication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male moderate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or more side effect (i.e., headache, nausea, anxiety, or erection). Urinary naltrexone levels did not differ between the groups. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant positive correlation between the parent compound and metabolite, suggesting parallel renal clearance. The results of this study suggest a possible mechanism for the side effects observed after acute administration of naltrexone.

The influence of a low dose of morphine on the self-selection of alcohol and sucrose solutions is investigated. When given a choice between sucrose sweetened ethanol and plain water, rats show a significant preference for the sweetened ethanol. However, when given a choice between sweetened ethanol and sweetened water, rats increase consumption of sweetened water. These results suggest that the low-dose morphine enhancement of sweetened alcohol solutions is mediated by the reinforcing properties of sucrose not ethanol. However, when rats receive small doses of morphine and a choice between unsweetened ethanol and water, the rats increase consumption of ethanol. Therefore, a low dose of morphine enhances the self-selection of both sucrose and ethanol solutions. This provides additional confirmation that opioids may enhance the rewarding properties of a variety of appetite reinforcers.

We investigated specific subjective effects of naltrexone pretreatment or placebo during various intervals on the breath alcohol level (BAL) curve in nonalcoholic volunteers. Fifteen high-risk (social drinkers with an alcoholic father) and 14 low-risk (no alcoholic relatives in at least two generations) subjects were tested in a double-blind placebo-controlled study of the effects of 50 mg oral naltrexone on response to a moderate dose of alcohol. Dependent measures included subjective stimulation and sedation subscales from the Biphasic Alcohol Effects Scale (BAES) and mood subscales from the Profile of Mood States (POMS). At rising BALs, high-risk subjects showed a naltrexone-related attenuation of BAES stimulation. This effect was not evident in low-risk subjects, who directionally showed the opposite effect, although nonsignificant. For both groups, there were no significant naltrexone-related effects for BAES sedation; however, naltrexone did affect several POMS scales on alcohol response, such as decreased vigor, and increased fatigue, tension, and confusion. Confusion was significantly elevated for the high-risk group during rising BALs of the naltrexone session. The results suggest a differential response to naltrexone, based on paternal history of alcoholism and level of stimulation experienced during alcohol drinking.

There is a great deal of interest in the use of naltrexone as a treatment for alcohol (ethanol) dependence since there is a rapidly expanding body of evidence to support its efficacy and tolerability in this indication. Naltrexone, a long-acting, nonselective opioid receptor antagonist has been shown to reduce alcohol intake when combined with behavioural treatment. Naltrexone may prevent the return to clinically significant drinking by blocking the pleasurable effects or "high' associated with alcohol drinking. Results from controlled studies showed that in alcohol dependent patients taking naltrexone 50 mg/day in combination with behavioural treatment, relapse rates were reduced by 50% compared with placebo treated patients. Historically, several factors have limited the use of effective pharmacological adjuncts in the treatment of alcohol dependence. These include safety considerations in this vulnerable population, and the fact that some treatment programmes discourage alcohol-dependent patients from taking medications. The most common adverse effects reported with the use of naltrexone at a dosage of 50 mg/day include nausea and vomiting. Naltrexone does not appear to be hepatotoxic in dosages recommended in the treatment of alcohol dependence, i.e. 50 mg/day. Thus, naltrexone appears to offer significant therapeutic benefits at a relatively low risk, when used judiciously and with behavioural treatment for alcohol dependent patients.

A 4-week, double-blind, placebo-controlled trial of amantadine was conducted in 61 cocaine dependent outpatients. Subjects received 100 mg of amantadine 3 times daily. A follow-up visit was conducted at week 8. There were no significant differences between groups in treatment retention, or in the number of benzoylecgonine positive urine samples. Self-reported drug and alcohol use declined in both groups. At week 8 follow-up, self-reported drug use was significantly lower in the placebo group. Amantadine was not effective, and discontinuation of it may have been associated with an increase in cocaine use.

The pooled results from our Veterans Affairs studies are presented for 99 men. The naltrexone-treated subjects reported a reduction in alcohol craving and drinking, as well as less euphoria when they ingested alcohol. Relapse rates were significantly lower for the naltrexone-treated subjects than they were for placebo-treated subjects. Together with the consistent results from other double-blind trials of naltrexone, we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients. Although administration of naltrexone was shown to improve treatment outcome, subjects who attended all 12 research visits demonstrated larger treatment effects. These data suggest that the use of naltrexone as a pharmacological adjunct to psychosocial intervention is an effective treatment for alcohol dependence. The effectiveness of naltrexone may be improved by designing a treatment program that enhances compliance with the medication.