Alcohol craving--a renaissance.
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Alcoholism↗
Biomedical subjects
R F Anton
Publications and source records attributed to R F Anton.
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.
Adult↗
Multiple previous alcohol detoxifications are associated with decreased medial temporal and paralimbic function in the postwithdrawal period.
BACKGROUND: Functional neuroimaging studies after alcohol cessation have demonstrated that chronic alcohol use globally reduces neuronal activity for several weeks. Less is known about the effects of previous alcohol use patterns on regional brain activity. Multiple previous alcohol detoxifications are associated with a worse clinical course and increased risk of seizures, perhaps due to sensitization of key brain structures. We performed the following imaging study in alcoholics in the postwithdrawal period to determine if blood flow in medial temporal structures would differ as a function of previous alcohol use (i.e., whether regions were kindled or sensitized due to multiple detoxifications). METHODS: Fourteen adults meeting DSM-IV criteria for alcohol dependence (mean age 35, 8 SD; 10 men) and participating in a double-blind detoxification medication study underwent a brain perfusion Tc99 m-ECD (Neurolite) single photon emission computed tomography scan on days 7 through 9 (mean 7.6, .5 SD) after their last drink and 2 to 3 days since their last detoxification medication. Seven nonpsychiatrically ill, nonalcohol-dependent healthy adults were scanned as control subjects. RESULTS: Alcoholics compared with controls had widely reduced relative activity in cortical secondary association areas and relatively increased activity in the medial temporal lobes (p < 0.01). Five alcoholic patients with > or = 2 previous detoxifications were compared with five patients in their first detoxification (age and detoxification medication matched). Multiple detoxification patients had significantly lower relative activity in bilateral anterior temporal poles and medial temporal lobes and in visual cortex (p < 0.01) compared with first episode patients. CONCLUSIONS: These studies are consistent with other studies comparing alcoholics and controls. They also suggest that on day 7 of detoxification, alcoholic subjects with multiple previous detoxifications have decreased visual cortex, medial temporal lobes, and anterior paralimbic blood flow, compared with those in their first detoxification. Further studies seem warranted to confirm these initial exploratory results.
Adult↗
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.
Adult↗
What is craving? Models and implications for treatment.
Although many alcoholics experience craving, researchers have not yet developed a common, valid definition of the phenomenon. Numerous models of the mechanisms underlying craving have been suggested, however. One of those models--the neuroadaptive model--suggests that the prolonged presence of alcohol induces changes in brain-cell function. In the absence of alcohol, those changes cause an imbalance in brain activity that results in craving. Furthermore, the adaptive changes generate memories of alcohol's pleasant effects that can be activated when alcohol-related environmental stimuli are encountered, even after prolonged abstinence, thereby leading to relapse. Similarly, stressful situations may trigger memories of the relief afforded by alcohol, which could also lead to relapse. Neurobiological and brain-imaging studies have identified numerous brain chemicals and brain regions that may be involved in craving. Psychiatric conditions that affect some of these brain regions, such as depression or anxiety, also may influence craving. A better understanding and more reliable assessment of craving may help clinicians tailor treatment to the specific needs of each patient, thereby reducing the risk of relapse.
Alcoholism↗
The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics.
Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.
Adult↗
Female alcoholic outpatients and female college students: a correlational study of self-reported alcohol consumption and carbohydrate-deficient transferrin levels.
OBJECTIVE: We sought to test the efficacy of two biochemical markers of alcohol consumption, gamma glutamyl transpeptidase and carbohydrate deficient transferrin, as indicators of heavy alcohol consumption in a female population. METHOD: Using a sample of female outpatient alcoholics (n = 36) and a comparison group of female college students (n = 50), alcohol intake was monitored by self-report at approximately 90-day intervals over a period of 12 months. Gamma glutamyl transpeptidase (GGTP) and carbohydrate-deficient transferrin (CDT) values were determined for each sampling period. The criterion for heavy alcohol consumption was set at 140 g/alcohol/week for a 90-day period. Receiver operating characteristic (ROC) curves were plotted, area under the curve (Az) computed, and sensitivity and specificity calculated for both CDT and GGTP. ROC curves provide a graphical illustration of the association between the specificity and sensitivity of any diagnostic test over all possible cutpoint values. RESULTS: A significant, positive correlation between the amount of alcohol consumed and GGTP activity was recorded for the outpatient alcoholic group. Among the college students, there was a significant, positive correlation between CDT levels and alcohol consumed for the second reporting period. The sensitivity of the individual biochemical markers was low but, when used in combination, sensitivity was 66% and specificity, 80%. When a more stringent criterion for heavy alcohol consumption was applied (420 g/alcohol/week), the sensitivity of CDT actually decreased. CONCLUSIONS: CDT, used alone, is a poor indicator of heavy alcohol consumption in female subjects. When GGTP measures are used in conjunction with CDT, detection of heavy alcohol consumption may be enhanced to useful levels.
Adult↗
Treatment of alcohol withdrawal.
Appropriate treatment of alcohol withdrawal (AW) can relieve the patient's discomfort, prevent the development of more serious symptoms, and forestall cumulative effects that might worsen future withdrawals. Hospital admission provides the safest setting for the treatment of AW, although many patients with mild to moderate symptoms can be treated successfully on an outpatient basis. Severe AW requires pharmacological intervention. Although a wide variety of medications have been used for this purpose, clinicians disagree on the optimum medications and prescribing schedules. The treatment of specific withdrawal complications such as delirium tremens and seizures presents special problems and requires further research.
Alcoholism↗
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.
Adult↗
Behavior and physiology of social stress and depression in female cynomolgus monkeys.
The hypothesis that social subordination is stressful, and results in a depressive response in some individuals, was examined in socially housed female cynomolgus monkeys. Social status was manipulated such that half of the previously subordinate females became dominant and half of the previously dominant females became subordinate. Current subordinates hypersecreted cortisol, were insensitive to negative feedback, and had suppressed reproductive function. Current subordinates received more aggression, engaged in less affiliation, and spent more time alone than dominants. Furthermore, they spent more time fearfully scanning the social environment and displayed more behavioral depression than dominants. Current subordinates with a history of social subordination were preferentially susceptible to a behavioral depression response. The results of this experiment suggest that the stress of social subordination causes hypothalamic-pituitary-adrenal and ovarian dysfunction, and support the hypothesis that chronic, low-intensity social stress may result in depression in susceptible individuals.
Adrenocorticotropic Hormone↗
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.
Adult↗
Proposed recommendations for research on biochemical markers for problematic drinking.
Biochemical markers can serve as valuable tools in screening for problematic drinking, determining whether a health problem is likely alcohol related, and monitoring alcoholics for relapse during and after treatment. Furthermore, biochemical markers can assist in forensic investigations; in identification of public health, safety, and transportation workers who may drink excessively and who, as a result, may put others at risk; in evaluation of efficacy of treatments for alcohol abuse; and in recognition of early phase alcohol-related tissue damage. Within all of these contexts, a biochemical marker or set of markers may corroborate verbal reports or may provide valuable independent information on alcohol use when an individual is unable or unwilling to offer valid data about alcohol consumption.
Alcoholism↗
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.
Adult↗
Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.
Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.
Adult↗
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.
Adult↗
New methodologies for pharmacological treatment trials for alcohol dependence.
As the number of pharmacological agents for the treatment of alcoholism continues to proliferate, there is an increasing need to design studies that accurately measure the efficacy of these agents. Key study design issues include selecting subjects, calculating patient retention, determining medication compliance, maintaining adequate sample size to ensure that a clinically meaningful therapeutic effect will not be missed, and measuring the study outcome, including the amount of alcohol consumed and levels of craving. Because there is evidence that self-report of alcohol consumption and medication compliance can be unreliable in subjects, biological methods have been used. One type of direct measurement, carbohydrate-deficient transferrin levels, has been found to be a reasonably sensitive indicator of alcohol consumption that may provide meaningful outcome information. The ingestion of riboflavin with medication and its urinary measurement is an accepted method of compliance detection. Improved study design will lead to continued advances in pharmacotherapy for the treatment of patients with alcoholism.
Alcohol Deterrents↗
The use of carbohydrate deficient transferrin as an indicator of alcohol consumption during treatment and follow-up.
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Alcohol Drinking↗
Pharmacotherapy of alcoholism--10 years of progress.
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Alcohol Deterrents↗