Joseph R. Volpicelli

A Functional Polymorphism of the μ -Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

This study examined the association between two specific polymorphisms of the gene encoding the μ-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+118G (Asn40Asp) and C+17T (Ala6Val) SNPs in the gene encoding the μ-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 μ-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence

Abstract 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.

Naltrexone in the treatment of alcoholism: A clinical review

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.

Comparative Effectiveness and Costs of Inpatient and Outpatient Detoxification of Patients with Mild-to-Moderate Alcohol Withdrawal Syndrome

We compared the effectiveness, safety, and costs of outpatient (n = 87) and inpatient (n = 77) detoxification from alcohol in a randomized, prospective trial involving 164 male veterans of low socioeconomic status. The outpatients were evaluated medically and psychiatrically and then were prescribed decreasing doses of oxazepam on the basis of daily clinic visits. The inpatient program combined comprehensive psychiatric and medical evaluation, detoxification with oxazepam, and the initiation of rehabilitation treatment. The mean duration of treatment was significantly shorter for outpatients (6.5 days) than for inpatients (9.2 days). On the other hand, significantly more inpatients (95 percent) than outpatient (72 percent) completed detoxification. There were no serious medical complications in either group. Outcome evaluations completed at one and six months for 93 and 85 percent of the patients, respectively, showed substantial improvement in both groups at both follow-up periods. At one month there were fewer alcohol-related problems among inpatients and fewer medical problems among outpatients. However, no group differences were found at the six-month follow-up, nor were differences found in the subsequent use of other alcoholism-treatment services. Costs were substantially greater for inpatients (

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

3,319 to

Reliability and validity of the cocaine selective severity assessment

3,665 per patient) than for outpatients (

Naltrexone blocks the post-shock increase of ethanol consumption

175 to

A Comparison of the Effects of the Opioid Antagonists Naltrexone, Naltrindole, and β-Funaltrexamine on Ethanol Consumption in the Rat

388). We conclude that outpatient medical detoxification is an effective, safe, and low-cost treatment for patients with mid-to-moderate symptoms of alcohol withdrawal.

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

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.

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

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.