A randomized trial of naltrexone for smoking cessation. Naltrexone effects on short-term and long-term smoking cessation. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Naltrexone treatment for alcoholics: effect on cigarette smoking rates. Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. Naltrexone for alcohol dependence: a randomized controlled trial. Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women.
To evaluate the efficacy and safety of orally administered naltrexone, alone or in combination with nicotine patches, as a treatment for cigarette smoking.
                Randomized, partially-blinded, 2 x 2 factorial trial using naltrexone (active vs. placebo) and nicotine patches (active vs. none).
                One hundred cigarette smokers.
                Twelve weeks of either placebo-only, naltrexone-only, placebo with nicotine patches or naltrexone with nicotine patches. The naltrexone dose was 50 mg taken once daily, and the nicotine patch dose was 21 mg/24-hour for the first 8 weeks and 14 mg/24-hour for the remaining 4 weeks. Brief behavioral intervention was provided at each visit.
                One-week point-prevalence smoking abstinence rates confirmed by an expired air carbon monoxide level of 8 parts per million (ppm) or less, daily cigarette smoking and cigarette craving.
                At the end of treatment, there was no effect of naltrexone on smoking abstinence. The smoking abstinence rates were 19% and 22% for the placebo only and naltrexone only treatment groups, respectively, and 48% and 46% for the placebo with nicotine patch and naltrexone with nicotine patch groups, respectively. However, the effect of the nicotine patch at this time was significant (p = 0.006), but not at the 6-month follow-up. No significant effect of naltrexone was observed on daily cigarette smoking on cigarette craving during the study.
                The opioid antagonist naltrexone was not found to be effective for smoking cessation and had no significant effect on daily cigarette consumption or craving. The results of the present study provide no support for the use of naltrexone, alone or in combination with nicotine patches, as a therapeutic treatment for smoking cessation. This study examined the efficacy of naltrexone, a long-acting opiate antagonist, as a smoking cessation aid in a double-blind placebo-controlled randomized trial. It was hypothesized that naltrexone would result in higher quit rates at the end of treatment and six months later.
                Subjects were 68 smokers aged 18 to 65 who smoked at least 20 cigarettes daily and wished to stop smoking. They took naltrexone or placebo daily for four weeks and were seen weekly for individual smoking cessation therapy.
                A statistical trend towards a higher overall cessation rate (cotinine < 15 ng/mL) at end-of-treatment was observed among subjects treated with naltrexone than placebo (46.7% vs. 26.3%, respectively, odds ratio = 2.5, p < .10); however, this difference was attenuated at six months (27% vs. 15%, respectively, odds ratio = 1.9, p = ns). Stratified analysis indicated the usefulness of naltrexone primarily for female smokers and those with a history of major depression. These effects remained six months later.
                These results provide, at best, mild promise for naltrexone as a smoking cessation drug and provide another instance of a differential response to nicotine dependence treatment according to gender and depression history. Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose.
                Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers.
                We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence.
                The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers. This double-blinded, placebo-controlled trial evaluated the efficacy of naltrexone as an adjunct to standard smoking cessation treatment. Participants (N = 110) were adult male and female nicotine-dependent smokers who expressed interest in quitting smoking. All subjects received six sessions of behavioral counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg for the first 2 weeks, 14 mg the third week, 7 mg the fourth week). Subjects were randomly assigned to the naltrexone or placebo group. The naltrexone group started at 25 mg daily for 3 days prior to the quit date, and increased to 50 mg/day on the quit date and following 8 weeks. At the end of medication treatment, the naltrexone group had better quit rates versus the placebo group (48% quit on naltrexone vs. 41% on placebo), but this difference was not statistically significant. However, men and women differed on several measures: in the placebo group, women had significantly lower quit rates than men (39% vs. 67%, p<.05), but in the naltrexone group, women had quit rates comparable with those of men (58% vs. 62%, p = ns). Further examination revealed that naltrexone significantly reduced men's and women's cessation-related weight gain and selectively reduced women's urge to smoke to relieve negative affect and withdrawal. The results suggest continued examination of naltrexone as an adjunct in smoking cessation, particularly in female smokers, who have historically shown worse outcomes with traditional treatment methods. Naltrexone (NTX), by its pharmacological action in the mesolimbic pathways, should decrease reinforcement from nicotine as well as from alcohol. By means of this mechanism, NTX could result in temporary increases in smoking followed by decreased smoking rates among alcoholics not motivated to quit smoking. The change from pretreatment in smoking rates of 73 recently abstinent alcoholics in a 12-week clinical trial of NTX vs. placebo during alcoholism treatment was compared during 8 of the 12 weeks. Only smokers compliant with NTX were included in the analyses. NTX was associated with decreased smoking at every time point, but the effect was significant at only one time point. When alcohol relapsers were excluded, NTX patients showed decreased smoking at every time point, but the effect was significant at only two time points, a reduction of about five cigarettes per day. When smoking stage of change was included in the analyses, NTX showed no significant main or interaction effects on smoking rate. Precontemplators showed significantly less change in smoking rate than all other patients at the first and last four time points. Therefore, NTX alone currently does not show promise for promoting smoking reduction among recently abstinent alcoholics who have not sought or been given smoking cessation treatment. Further research is needed on possible effects with smokers motivated to quit smoking and on other methods of promoting smoking cessation among alcoholics. Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians.
                Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence.
                Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response.
                Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism. 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. 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. This study examined whether the opioid receptor antagonist naltrexone is efficacious in smoking cessation and whether sex moderates the response. We assessed smoking quit rates and weight gain in a double-blind randomized trial comparing oral naltrexone (n = 162) with placebo (n = 154) in nicotine-dependent participants who wanted to quit smoking. The medication was gradually titrated up to 50 mg during the week before the quit date and then maintained at this dose for 12 weeks. For the first 4 weeks after the quit date, all participants received a nicotine patch to mitigate tobacco withdrawal and attended weekly individual cognitive-behavioral smoking cessation counseling sessions. After this time, participants continued with naltrexone or placebo through 12 weeks. Follow-up assessments were conducted at 26 and 52 weeks. During treatment, naltrexone (vs placebo) increased quit rates, attenuated smoking urge, and reduced weight gain. At follow-up, after medication discontinuation, the effect of naltrexone on improving quit rates was no longer evident. Men and women experienced different benefits from naltrexone; men showed greater reductions in smoking, whereas women showed greater reductions in weight gain. In sum, naltrexone showed acute efficacy in treating nicotine dependence, but after the medication was discontinued, the effect on quit rate was not maintained. Further study of naltrexone in smoking cessation treatment and reduction of cessation-related weight gain, as well as preclinical investigation of mechanisms underlying sex differences, is warranted.
Based on data from eight trials and over 1200 individuals, there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence, with a point estimate strongly suggesting no effect and confidence intervals that make a clinically important effect of treatment unlikely. Although further trials might narrow the confidence intervals they are unlikely to be a good use of resources.