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. A placebo-controlled randomized clinical trial of naltrexone in the context of different levels of psychosocial intervention. Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting. Naltrexone administration affects ad libitum smoking behavior. Happy ending: a randomized controlled trial of a digital multi-media smoking cessation intervention. Naltrexone depot for treatment of alcohol dependence: a multicenter, randomized, placebo-controlled clinical trial. A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. Extended treatment of older cigarette smokers. Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1-year outcomes. Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm. Effects of naltrexone with nicotine replacement on smoking cue reactivity: preliminary results. The use of naltrexone to treat ambulatory patients with alcohol dependence.
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. Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content.
                Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone (100 mg/d). Subjects were also randomly assigned to 1 of 3 psychosocial interventions. All patients were assessed for alcohol use, medication adherence, and adverse events at regularly scheduled research visits.
                There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome.
                Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response. Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.
                Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.
                The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).
                For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.
                Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. Oral naltrexone is effective in the treatment of alcohol dependence; however, a major limitation of its clinical utility is poor patient adherence to the daily dosing schedule. A biodegradable, long-acting naltrexone microsphere formulation was developed to achieve continuous naltrexone exposure for 1 month in the treatment of alcohol dependence.
                The single- and multiple-dose safety and pharmacokinetics of a long-acting naltrexone microsphere preparation were evaluated in healthy subjects. One group of subjects (n = 28) received a single dose of oral naltrexone 50 mg followed by a single gluteal intramuscular (IM) injection of long-acting naltrexone 190 or 380 mg or placebo. A different group of subjects (n = 14) received oral naltrexone 50 mg daily for 5 days, followed by IM long-acting naltrexone 380 mg or placebo every 28 days for a total of 4 doses. A 7-day washout period separated oral and IM administrations. Blood samples were collected to determine plasma concentrations of naltrexone and the primary metabolite, 6beta-naltrexol.
                After a single IM injection of long-acting naltrexone 380 mg, naltrexone plasma concentrations were measurable in all subjects for at least 31 days postdose. The pharmacokinetics were proportional to the dose and multiple dose observations were consistent with single dose observations. Mean apparent elimination half-lives for naltrexone and 6beta-naltrexol ranged from 5 to 7 days. Exposure to 6beta-naltrexol was reduced with IM injection compared with that oral administration. No serious adverse events occurred.
                This study demonstrated that the long-acting naltrexone formulation was well tolerated, displayed predictable pharmacokinetics, and resulted in no meaningful drug accumulation upon multiple dosing. Intramuscular administration avoids first-pass metabolism and changes the exposure ratio of 6beta-naltrexol to naltrexone compared with oral administration. By providing continuous exposure to naltrexone for several weeks following IM injection, this long-acting naltrexone formulation may offer therapeutic benefit to those patients who experience difficulty adhering to the daily administration schedule necessitated by oral naltrexone therapy. There are mixed results on the effects of opioid antagonists on acute nicotine response in humans. The present study examined the effects of a single dose of 50 mg oral naltrexone relative to placebo on smoking response in 22 chronic smokers during short-term nicotine abstinence, after acute smoking and subsequent smoking deprivation, and on smoking behavior in a choice paradigm. The results showed that naltrexone significantly reduced immediate postcigarette ratings of smoking craving and desire to smoke and increased light-headedness, dizziness, and head rush (ps < 0.05). Reductions in craving and smoking desire persisted during a subsequent 1 h nonsmoking interval. Naltrexone also was found to significantly reduce the total number of cigarettes smoked in the choice interval, which was supported by objective measures of both reduced CO and plasma nicotine levels (ps < 0.01). Exploratory analyses on potential individual difference factors revealed that smokers with the highest levels of craving during abstinence showed the most pronounced naltrexone attenuation of smoking response. The results support the continued exploration of naltrexone as an adjunct to smoking cessation, especially in identified smoker subgroups most sensitive to the effects of opioid antagonism. 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. Endogenous opioid peptides have been implicated in the reinforcement of smoking and opioid antagonists have been examined to determine their role in smoking behavior. To date, the relationship between smoking behavior and chronic opiate antagonist administration during ad libitum smoking has not been investigated. The purpose of this study was to examine the relationships between naltrexone, an opiate antagonist administered orally, and smoking behavior and mood states during ad libitum smoking. A repeated measures experimental design was used. Normal adult male and female volunteers, admitted to the Clinical Research Center, were randomly assigned to naltrexone-treated (n = 22) or placebo-control (n = 21) groups in a double-blind manner. Day 1 was considered acclimation to the unit and day 2 was baseline, or pre-drug administration. On days 3, 4, and 5, subjects received 50 mg naltrexone or a placebo at 0700 and 1600 hours. Plasma nicotine and expired air carbon monoxide levels were measured daily at 1900 hours. Number of cigarettes smoked, mood states, withdrawal symptomatology and self-reported satisfaction with smoking were also quantified daily. Results indicated that plasma nicotine levels (P = 0.005), number of cigarettes smoked daily (P = 0.003) and self-reported satisfaction with smoking (P = 0.043) were significantly lower among those treated with naltrexone, compared to the placebo-control group. Expired air carbon monoxide levels did not differ between the two groups. In addition, mood states and withdrawal symptoms did not differ between groups. These findings suggest that endogenous opioid peptides influence specific smoking behavior variables. To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention.
                Two-arm randomized control trial (RCT). Setting World Wide Web (WWW) study based in Norway.
                Subjects (n = 396) were recruited via internet advertisements and assigned randomly to conditions. Inclusion criteria were willingness to quit smoking and being aged 18 years or older.
                The treatment group received the internet- and cell-phone-based Happy Ending intervention. The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail, web-pages, interactive voice response (IVR) and short message service (SMS) technology. The control group received a self-help booklet. Additionally, both groups were offered free nicotine replacement therapy (NRT).
                Abstinence was defined as 'not even a puff of smoke, for the last 7 days', and assessed by means of internet surveys or telephone interviews. The main outcome was repeated point abstinence at 1, 3, 6 and 12 months following cessation.
                Participants in the treatment group reported clinically and statistically significantly higher repeated point abstinence rates than control participants [22.3% versus 13.1%; odds ratio (OR) = 1.91, 95% confidence interval (CI): 1.12-3.26, P = 0.02; intent-to-treat). Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group.
                As the first RCT documenting the long-term treatment effects of such an intervention, this study adds to the promise of digital media in supporting behaviour change. Studies of the efficacy of naltrexone for alcohol dependence have yielded variable findings, which may be due, in part, to variation in compliance with oral naltrexone. Efforts to improve naltrexone compliance have included the development of injectable, long-acting depot formulations.
                We conducted a multicenter trial in 315 subjects who were randomly assigned to receive an intramuscular injection of a depot formulation containing naltrexone (n = 158) or a placebo formulation (n = 157) monthly for 3 months. All patients received five sessions of manual-guided motivational enhancement therapy during the 12 weeks of the study. The outcomes of interest were based on self-reported alcohol use and gamma-glutamyl transpeptidase level. Missing data or data from subjects who discontinued the study were conservatively treated as heavy-drinking days.
                Groups were comparable on pretreatment demographic and clinical measures. The medication was well tolerated; 73.7% of subjects received all injections. The time to the first heavy-drinking day, the percentage of subjects with no heavy drinking throughout the study, and gamma-glutamyl transpeptidase levels favored the naltrexone depot, although the effects did not reach statistical significance. There was a significant advantage for naltrexone depot treatment on the time to the first drinking day. Naltrexone depot subjects also had significantly fewer drinking days during treatment and a significantly greater abstinence rate than the placebo group (18% vs. 10%).
                This is the first multicenter study of a depot formulation of naltrexone for the treatment of alcohol dependence. Using a conservative intent-to-treat analysis, the study showed an advantage for the active medication. Further research with this formulation is warranted. In several studies, patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo. An interaction between the naltrexone effect and the type of psychological therapy has been observed.
                A 6-month, double-blind, placebo-controlled, parallel-group study was performed at 10 different investigation sites. After a placebo run-in period of 1 week, 118 patients were randomized into 4 treatment groups-50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy (CBT) or supportive therapy. The CBT was performed over nine sessions according to the manual of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). The supportive therapy was defined as "the treatment as usual." Alcohol consumption, craving, carbohydrate-deficient transferrin, medication compliance by tablet count, and adverse clinical events were assessed at all visits. Other liver enzymes and psychiatric symptoms were also determined.
                Ninety-one (77%) patients completed the study, and 92 (78%) were 80% compliant with the medication regimen. A lower percentage of heavy-drinking days was shown in the naltrexone group (p = 0.045) compared with the placebo group, as was a lower craving score (p = 0.029). These results are supported by the lower levels of liver enzyme activities (p < 0.010 for aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase), but not by the carbohydrate-deficient transferrin levels, in the naltrexone group. The mean time period before the first day of heavy drinking was longer for the group treated with CBT (p = 0.010), especially in combination with naltrexone (p = 0.007). Naltrexone was well tolerated, and no patients discontinued the study due to side effects.
                This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected. The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment. Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.
                To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.
                Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.
                Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.
                Percent days abstinent from alcohol and time to first heavy drinking day.
                All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.
                Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.
                clinicaltrials.gov Identifier: NCT00006206. Tobacco dependence treatments achieve abstinence rates of 25-30% at 1 year. Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder. The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age, and to determine if gender differences in efficacy existed.
                Open randomized clinical trial.
                A free-standing, smoking treatment research clinic.
                A total of 402 smokers of > or = 10 cigarettes per day, all 50 years of age or older.
                Participants completed a 12-week treatment that included group counseling, nicotine replacement therapy (NRT) and bupropion. Participants, independent of smoking status, were then assigned randomly to follow-up conditions: (i) standard treatment (ST; no further treatment); (ii) extended NRT (E-NRT; 40 weeks of nicotine gum availability); (iii) extended cognitive behavioral therapy (E-CBT; 11 cognitive behavioral sessions over a 40-week period); or (iv) E-CBT plus E-NRT (E-combined; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability).
                Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24, 52, 64 and 104.
                The most clinically important findings were significant main effects for treatment condition, time and the treatment x time interaction. The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [(week 24 (58%), 52 (55%), 64 (55%) and 104 (55%)], and was significantly more effective than E-NRT and ST across that period. No other treatment condition was significantly different to ST. No effects for gender were found.
                Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women. NRT does not add to the efficacy of extended CBT, and may hamper its efficacy. Research is needed to determine if these results can be replicated in a sample with a greater range of ages, and improved upon with the addition of medications other than NRT. Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts.
                A 2 x 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2-week partial hospital program (n = 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n = 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited.
                Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self-efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy.
                The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes. Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated.
                This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes.
                In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette.
                The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices.
                These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies. Although several studies have examined the effects of opioid antagonists on smoking behavior, there have been no reports of the potentially therapeutic combination of naltrexone and nicotine replacement therapy. The primary objective of the present study was to determine whether naltrexone reduced reactivity to smoking cues among abstinent smokers treated with nicotine replacement. Twenty participants were instructed to abstain from smoking cigarettes for 9 h while using nicotine replacement therapy. Participants were subsequently treated with either naltrexone (50 mg) or placebo before being exposed to smoking cues. Results indicated that the smokers who received the placebo responded to smoking cue exposure with increases in urge to smoke and increases in negative affect. Participants who received naltrexone did not show any increase in urge or negative affect and showed a decrease in withdrawal symptoms after exposure to smoking cues. Although preliminary, the findings suggest that naltrexone may work in combination with nicotine replacement therapies to block the effects of smoking stimuli in abstinent smokers. The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing craving symptoms among Puerto Rican male veterans with alcohol dependence.
                This is a double blind placebo control study with a convenience sample of eleven patients divided in two groups (placebo and Naltrexone). Scales consisting of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization were administered at baseline, and weekly for four weeks as follow up.
                There were no statistically significant differences between the two groups on any of the outcome variables at baseline or follow up measurements. A statistical trend was noted toward a decrease in somatization. A decrease in craving symptoms was observed in the experimental group.
                Even though our results did not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a small number of patients did benefit from the medication. The results could have been affected by the small sample size.
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.