Alcohol craving predicts drinking during treatment: an analysis of three assessment instruments.

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.

Predicting treatment response to naltrexone: the influence of craving and family history.

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.

Alcohol abuse and alcoholism: an overview.

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.

Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption.

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.

Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates.

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.

Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity.

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.

Cocaine withdrawal symptoms and initial urine toxicology results predict treatment attrition in outpatient cocaine dependence treatment.

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.

The effect of gamma-vinyl-GABA on the consumption of concurrently available oral cocaine and ethanol in the rat.

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.

Double-blind clinical trial of sertraline treatment for alcohol dependence.

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.

Amantadine in the treatment of cocaine-dependent patients with severe withdrawal symptoms.

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.

The effect of antagonists selective for mu- and delta-opioid receptor subtypes on alcohol consumption in C57BL/6 mice.

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.

6-beta-naltrexol reduces alcohol consumption in rats.

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.

Gender and psychiatric comorbidity: impact on clinical presentation 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.

Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype.

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.

Improving naltrexone response: an intervention for medical practitioners to enhance medication compliance in alcohol dependent patients.

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.

Psychosocially enhanced treatment for cocaine-dependent mothers: evidence of efficacy.

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 NMDA receptor partial agonist, 1-aminocyclopropanecarboxylic acid (ACPC), reduces ethanol consumption in the rat.

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.

Psychometric properties of the Penn Alcohol Craving Scale.

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.

Open trials as a method of prioritizing medications for inclusion in controlled trials for cocaine dependence.

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.