Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism.

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.

Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial.

OBJECTIVE: The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy. METHOD: In this study, 131 recently abstinent alcohol-dependent outpatients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N = 68) or placebo (N = 63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial. RESULTS: The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone-treated subjects drank less, took longer to relapse, and had more time between relapses. They also exhibited more resistance to and control over alcohol-related thoughts and urges, as measured by a subscale of the Obsessive Compulsive Drinking Scale. Over the study period, 62% of the naltrexone group did not relapse into heavy drinking, in comparison with 40% of the placebo group. CONCLUSIONS: Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy. Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking. Thus, the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic.

Factor structure and predictive validity of the Obsessive Compulsive Drinking Scale.

BACKGROUND: The Obsessive Compulsive Drinking Scale (OCDS) is a 14-item, self-report instrument developed to measure obsessive thoughts about alcohol use and compulsive behaviors toward drinking. The objective of this study was to ascertain the factor structure underlying responses to the OCDS, and to further assess whether subscale scores derived from this structure were distinctive, internally consistent, predictive of future drinking, and able to differentiate between patients receiving naltrexone versus placebo in a controlled alcoholism treatment trial. METHODS: OCDS data were collected from a total of 132 alcohol-dependent subjects at up to 15 assessment points during the study. Interitem correlations were pooled across assessment periods, and an iterated principal axis factor analysis with oblique promax rotation was performed. The factor analysis suggested that three primary factors could parsimoniously account for the common variance in item responses. Subscale scores were formed by summing responses to the most salient items on each factor. RESULTS: The three common factors were interpreted as "resistance/control impairment," "obsession," and "interference." The subscale scores corresponding to these three factors were internally consistent, and their correlation with other baseline measures of alcohol use and severity suggested that they were distinct. Scores on each subscale reliably distinguished between subjects who remained abstinent, exhibited "slip" drinking, or relapsed to heavy drinking during the 12 weeks of active treatment. Additionally, scores on the resistance/control impairment subscale distinguished between those patients receiving treatment with naltrexone or placebo. Scores from each subscale also were able to predict the hazard for heavy drinking in the following week of treatment. CONCLUSIONS: The three OCDS factors are easily estimated with the summated scoring approach, and the resulting subscales appear to be internally consistent and distinctive. Moreover, the group differentiation capability and predictive utility of the subscale scores suggest that they might be useful as either predictor or outcome variables in alcoholism treatment trials. The duration of time for which a given OCDS assessment maintains its predictive utility awaits further confirmation.

Further validation of the Obsessive-Compulsive Drinking Scale (OCDS). Relationship to alcoholism severity.

The authors administered the Obsessive-Compulsive Drinking Scale (OCDS), a self-rated questionnaire that quantifies some cognitive and behavioral dimensions of "craving" for alcohol, to 124 alcohol-dependent subjects in three pharmacological treatment studies. The OCDS total scores had significant correlations with both the Alcohol Dependence Scale (r = 0.42; P < 0.0001) and the alcohol subscale of the Addiction Severity Index (r = 0.44; P < 0.0001). Previous alcoholism treatment was associated with higher OCDS Total and Obsessive subscale scores. These data support the congruent validity of the OCDS with previously well established measures of alcohol dependence severity and suggest that this measurement of craving may help in formulating appropriate treatment plans for alcoholic patients.

A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal.

Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.

Carbohydrate-deficient transferrin as an indicator of drinking status during a treatment outcome study.

Biological markers of alcohol consumption have been used in both clinical and research settings to aid in the identification of relapse drinking. Although carbohydrate-deficient transferrin (CDT) has been shown to be a sensitive and specific marker for the identification of heavy drinkers, little data are available as to its utility as a marker for relapse drinking during treatment, particularly in comparison with the more widely used serum gamma-glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before entering, and every 4 weeks during, a 12-week outpatient treatment trial combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were again measured 14 weeks after completion of treatment. During the 12-week treatment period, CDT showed a significant difference in those individuals who abstained from drinking (30% decrease), compared with those who relapsed (10% increase). GGT decreased on average in all individuals, and the change from treatment entry did not differ significantly across the drinking outcome groups. The change in CDT, but not GGT, from study entry to termination, significantly correlated with total alcohol consumption during the trial. At the 14-week posttreatment, follow-up evaluation CDT showed about a 60% elevation and GGT showed a 30% elevation, on average, from study entry values in those individuals who had relapse drinking by self and/or collateral report. The change in both markers differed between those individuals who remained abstinent or relapsed during the poststudy period. In general, the change in CDT from pretreatment levels seemed more sensitive to drinking status during treatment and follow-up than GGT. This indicates that CDT may be more sensitive marker for evaluating drinking status during both clinical and research treatment trials.

Alcohol-related seizures and the kindling effect of repeated detoxifications: the influence of cocaine.

The purpose of this study was to determine if individuals with concurrent alcohol and cocaine use differ in regard to seizure risk compared to individuals who abuse only alcohol, and to explore the relationship between multiple detoxifications and seizure risk in the context of concurrent cocaine use. In this study, alcoholic cocaine users had a decreased risk of seizure compared to alcoholics without cocaine use (P < 0.005). Seizures were rare in individuals who did not abuse alcohol. Alcoholic cocaine users reported a younger age at first seizure compared to alcoholics without cocaine use (P < 0.04). Alcoholic patients with seizures had significantly more previous detoxification experiences compared to matched alcoholic patients without seizures (P = 0.0001). Concurrent cocaine use did not appear to have an independent effect on the risk of seizure. The findings in this study suggest that concurrent cocaine use may accelerate the development of alcohol-related seizures in predisposed individuals but does not appear to substantially increase overall risk. Multiple previous detoxifications are associated with an increased risk of seizures in alcoholics both with and without concurrent cocaine use.

The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies.

BACKGROUND: the 14-item Obsessive Compulsive Drinking Scale (OCDS) is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol "craving". This study validated further its utility as an alcoholism severity and treatment outcome instrument. METHODS: Alcoholism severity and analogue craving scales were administered at baseline, and the OCDS was given at baseline and weekly to 41 alcohol-dependent individuals who participated in a 12-week pharmacologic and cognitive-behavioral treatment trial. Repeated-measures analysis of variance was used to examine group differences in the OCDS scores of those individuals who remained abstinent or drank during the trial. RESULTS: At baseline, the OCDS was correlated with the alcohol composite score of the addiction severity index (r=.48), the alcohol dependence scale (r=.42), the analogue craving measures (range r=.40 to .57), and prestudy alcohol consumption (r=.60). Most importantly the OCDS total and subscale scores were significantly different between individuals who had relapse drinking, who had "slip" drinking, and who remained abstinent, with relapsers showing the highest scores. CONCLUSIONS: The OCDS scores appear to be sensitive to alcoholism severity and change during abstinence and relapse drinking. Since the shared variance with analogue craving measures is only about 20% to 30%, it appears to be measuring a largely independent dimension of alcohol dependence. Its ease of use (5 minutes per self-rating), reliability, validity, and analytic capabilities support its utility as a tool to measure severity and improvement during alcoholism treatment trials.

The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior.

It has been suggested that a crucial dimension of alcohol "craving" includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. An interview-based rating scale, the Yale-Brown Obsessive Compulsive Scale-heavy drinkers (YBOCS-hd), has been found useful in quantifying this concept in alcohol-dependent individuals. A self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) has been developed by us as a modification of the YBOCS-hd. The YBOCS-hd showed excellent interrater reliability in our hands. The correlation between the YBOCS-hd and the OCDS total scores obtained on 60 alcohol-dependent individuals was 0.83. The test-retest correlation for the OCDS total score was 0.96, and the obsessive and compulsive subscales test-retest correlations were 0.94 and 0.86, respectively. The internal consistency of the items in the OCDS was high (0.86) and did not improve significantly with removal of individual items. The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only approximately 20%, indicating that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent individuals. When used during a prospective 12-week treatment research study, initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence, because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate-deficient transferrin and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences.

Carbohydrate-deficient transferrin (CDT) has been described as a more specific and sensitive marker of recent heavy alcohol consumption as compared with the current tests now available, such as gamma-glutamyltransferase (GGT). Most of the data generated from European populations have not compared the utility of CDT and GGT in the detection of heavy alcohol consumption as a function of gender. We examined the ability of both CDT and GGT to discriminate between 42 men and 18 women with heavy alcohol consumption (> 60 g/day) admitted to an alcohol detoxification center and a group of controls matched for age, race, and gender. CDT was higher, but GGT lower, in control females compared with males. Both CDT and GGT were higher in patients of both genders. At specificities > 90%, the sensitivity of CDT for detecting male alcohol abusers was 79% and for female alcohol abusers 44%. For GGT, the sensitivities were 65% and 44%, respectively. When both tests were used simultaneously, the sensitivity for the detection of alcohol abusers increased to 95% for males and 72% for females. Receiver Operator Characteristic analysis tended to confirm the superiority of CDT over GGT in the detection of heavy alcohol consumption in males, but not in females. A positive relationship was found between serum iron levels and CDT in control females but in no other group. The concordant findings of this American study with those in similar French and Finnish clinical populations, utilizing similar assay techniques, suggest that the measurement of CDT is clinically more useful than GGT in detecting recent heavy alcohol consumption in males.(ABSTRACT TRUNCATED AT 250 WORDS)