Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial. A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study. Naltrexone for alcohol dependence: a randomized controlled trial. Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial. Naltrexone combined with either cognitive behavioral or motivational enhancement therapy for alcohol dependence. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.
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.
                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.
                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.
                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. A 12-week, multicenter, double-blind, randomized, parallel-group clinical trial to compare naltrexone and placebo was carried out to determine the efficacy, safety, and tolerability of naltrexone together with a psychosocial intervention in the treatment of alcoholism.
                A total of 202 alcohol-dependent patients were assigned to 12 weeks' treatment with either naltrexone or placebo. The relapse rate was evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were evaluated in the 192 patients who were considered to be assessable.
                The survival function for patients who were treated with naltrexone was significantly better than that of the patients who were treated with placebo (Kaplan-Meier log rank = 4, df = 1, p < 0.05). In addition, 7.9% of patients who were treated with naltrexone relapsed as compared with 18.8% of those who received placebo [chi = 5.89, df = 2, p = 0.050]. In comparing naltrexone with placebo-treated patients, the most common adverse events were abdominal pain [8.6% vs. 1%; (chi = 6.1, df = 1, p < 0.05)] and headache [7.5% vs. 1% (chi = 5.1, df = 1, p < 0.05)].
                Naltrexone was well-tolerated, as the rate of adverse events was low, and safe, as it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Naltrexone seemed to reduce relapse rate to heavy drinking, but we found no differences in other alcohol consumption variables between naltrexone- and placebo-treated groups. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant. In a placebo-controlled, double-blind German multicenter study (seven sites) the efficacy of naltrexone as an adjunctive treatment in alcoholism to maintain abstinence was assessed for 12 weeks. A total of 171 detoxified patients (97.7% met the DSM-III-R criteria for alcohol dependence) were included. Patients had been abstinent for a mean of 19.5 +/- 9.4 days at study entry. Eighty-four and 87 patients were randomized to receive naltrexone (50 mg/day) and placebo, respectively. Each site was instructed to provide its usual psychosocial alcohol treatment program. The primary effectiveness measure was the time to first heavy drinking as derived from self-reports of drinking (timeline-follow-back method). Secondary effectiveness measures included time to first drink, amount of alcohol consumption, intensity of craving, severity of alcoholism problems, and liver enzymes. Thirty-three (38%) placebo patients and 28 (33%) naltrexone patients discontinued the study. At endpoint, 62% of the patients in each group did not have an episode of heavy drinking. Also, there were no significant differences between the study groups concerning secondary effectiveness measures as well as compliance and adverse clinical events--with the exception of the gamma-GT, which was significantly greater reduced in the naltrexone group throughout the study. Based upon an intention-to-treat population, this study confirms the safety but not the efficacy of naltrexone in prevention of alcohol relapse. Nevertheless, the question arises whether self-reports of drinking are more reliable than gamma-GT as a measure of recent alcohol consumption. We examined the efficacy of naltrexone (an opioid antagonist) for alcohol dependence in a sample of alcohol-dependent men.
                A 12-week randomized placebo-controlled clinical trial.
                The outpatient clinic of a combined war veteran and general teaching hospital in Melbourne, Australia.
                Male alcohol-dependent subjects recruited from the community and from veteran groups.
                Alcohol-dependent subjects were treated with 50 mg of naltrexone or placebo daily for 12 weeks. Both treatment groups attended a weekly education support group. Subjects were assessed weekly.
                Primary study outcomes were the maintenance of abstinence and relapse to drinking.
                Fifty-five subjects were randomized to naltrexone and 56 to placebo. Forty subjects did not complete 12 weeks of therapy (17 naltrexone, 23 placebo). In the intention-to-treat sample (N = 111) fewer naltrexone treated subjects relapsed (p = 0.001). Among patients who completed the 12-week trial, naltrexone reduced the consumption of alcohol. Naltrexone was well tolerated and there were few adverse experiences.
                These findings demonstrate that naltrexone is effective in preventing relapse to drinking in the setting of limited psychosocial treatment. Further studies should examine the duration of treatment needed to maintain the effect long term. Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time (12 weeks). In this study, 121 nonabstinent outpatients with alcohol dependence (DSM-IV) were treated with sessions of cognitive coping skills (N = 67) or supportive therapy (N = 54) and either naltrexone 50 mg/day (N = 63) or placebo (N = 58) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol (i.e., targeted medication) in a prospective one-center, dual, double-blind, randomized clinical trial. The dropout rate for all subjects was 16.5% during the first 12-week period and approximately twice that level by the end of the study. There were no significant group differences in study completion and therapy participation rates. After the continuous medication (12 weeks), the coping/naltrexone group had the best outcome, and coping/placebo had the worst. This difference remained during the targeted medication period (the following 20 weeks). Naltrexone was not better than placebo in the supportive groups, but it had a significant effect in the coping groups: 27% of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks, compared with only 3% of the coping/placebo patients. The authors' data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy. In addition, their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking. Although naltrexone has been shown to be effective in the treatment of alcohol dependence, less is known about its efficacy when combined with different behavioral therapies. Previous work has suggested that naltrexone works best when combined with weekly cognitive behavioral therapy (CBT). This study examined the efficacy of naltrexone when combined with CBT or a motivational enhancement therapy involving less patient contact. Outpatient alcoholics (N = 160) were randomly assigned to either naltrexone (50 mg/d) or placebo and either CBT (12 sessions) or motivational enhancement therapy (4 sessions), in a 4-cell design, and treated over a 12-week period. Subjects were evaluated periodically for alcohol consumption, craving, and biologic markers of drinking (carbohydrate-deficient transferrin and gamma-glutamyltransferase). There was high retention and adherence to therapy and medication in the trial with no significant difference across the treatment groups. Naltrexone, independent of therapy assignment, increased the time to first relapse. However, the CBT-naltrexone group did better than the other groups on a variety of outcome measures. Fewer CBT-naltrexone-treated subjects relapsed, and those that did had both fewer, and more time between, subsequent relapses. This randomized controlled trial is consistent with previous reports about the utility of combining naltrexone with CBT. Despite being more efficient to administer, the combination of motivational enhancement therapy and naltrexone is less effective than CBT and naltrexone. Because CBT and naltrexone share common mechanisms of action, such as craving reduction and relapse prevention, these therapies are likely to be well suited to use in combination. Ninety-seven alcohol-dependent patients were treated for 12 weeks in a double-blind, placebo-controlled study evaluating naltrexone and two manual guided psychotherapies in the treatment of alcohol dependence. Patients were randomized to receive either naltrexone or placebo and either coping skills/relapse prevention therapy or a supportive therapy designed to support the patient's own efforts at abstinence without teaching specific coping skills. Naltrexone proved superior to placebo in measures of drinking and alcohol-related problems, including abstention rates, number of drinking days, relapse, and severity of alcohol-related problems. Medication interacted with the type of psychotherapy received. The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy. For those patients who initiated drinking, however, patients who received naltrexone and coping skills therapy were the least likely to relapse. To determine whether naltrexone is beneficial in the treatment of alcohol dependence in the absence of obligatory psychosocial intervention.
                Multicentre, randomised, double-blind, placebo-controlled trial.
                Hospital-based drug and alcohol clinics, 18 March 1998 - 22 October 1999.
                107 patients (mean age, 45 years) fulfilling Diagnostic and statistical manual of mental disorders (4th edition) criteria for alcohol dependence.
                Patients with alcohol dependence were randomly allocated to naltrexone (50 mg/day) or placebo for 12 weeks. They were medically assessed, reviewed and advised by one physician, and encouraged to strive for abstinence and attend counselling and/or Alcoholics Anonymous, but this was not obligatory.
                Relapse rate; time to first relapse; side effects.
                On an intention-to-treat basis, the Kaplan-Meier survival curve showed a clear advantage in relapse rates for naltrexone over placebo (log-rank test, chi(2)(1) = 4.15; P = 0.042). This treatment effect was most marked in the first 6 weeks of the trial. The median time to relapse was 90 days for naltrexone, compared with 42 days for placebo. In absolute numbers, 19 of 56 patients (33.9%) taking naltrexone relapsed, compared with 27 of 51 patients (52.9%) taking placebo (P = 0.047). Naltrexone was well tolerated.
                Unlike previous studies, we have shown that naltrexone with adjunctive medical advice is effective in the treatment of alcohol dependence irrespective of whether it is accompanied by psychosocial interventions. Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.
                To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients.
                A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection.
                An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention.
                The event rate of heavy drinking days in the intent-to-treat population.
                Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups.
                Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.
Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.