Dose-dependent reduction of hazardous alcohol use in a placebo-controlled trial of naltrexone for smoking cessation

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
The International Journal of Neuropsychopharmacology (Impact Factor: 4.01). 10/2008; 12(5):589-97. DOI: 10.1017/S146114570800936X
Source: PubMed


The opiate antagonist naltrexone (Ntx) has demonstrated efficacy in the treatment of alcohol dependence and as a component of treatment to reduce heavy drinking. At present, there are no published dose-ranging clinical trials of the oral preparation for treatment of problem drinking. The present study evaluated the effects of Ntx on alcohol use among the subset of hazardous drinkers (n=102) who participated in a placebo-controlled, dose-ranging trial of oral Ntx (25-mg, 50-mg and 100-mg doses) combined with open-label transdermal nicotine patch for enhancing smoking cessation. On the primary outcome--no hazardous drinking (drinking that exceeded weekly or daily limits) during treatment--25 mg and 50 mg Ntx were superior to placebo (each p<0.05). These findings remained after controlling for baseline predictors or smoking abstinence during treatment. Time to remission of hazardous drinking was examined as a secondary outcome with definitions of hazardous drinking based on weekly limits, daily limits and the combination of weekly and daily limits and the results were consistent with the primary findings. In conclusion, the findings suggest that Ntx can reduce the risk of hazardous drinking in smokers who are not seeking or receiving alcohol treatment, providing strong evidence for the pharmacological effects of Ntx on drinking. This effect appears to favour lower doses that may be better tolerated and less expensive than the higher 100-mg dose. Given its efficacy and favourable side-effect profile, the 25-mg dose should be considered for future studies of combination therapy.

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Available from: Robert F Leeman
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    • "The present results showing drinking reductions with naltrexone that were exclusive to HDS support 2 prior studies examining only HDS (King et al., 2009a; O'Malley et al., 2009), and the improvement in quit rates in HDS supports our previous study in a smaller sample (King et al., 2009a). By comparing HDS to moderate-to-light and nondrinking smokers, we have demonstrated that HDS selectively benefit from naltrexone as an adjunctive treatment for smoking cessation and may be an important smoker subgroup to target in future clinical trials research. "
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    ABSTRACT: Background Heavy drinking smokers (HDS) have more difficulty quitting smoking than lighter drinkers or abstainers. The opioid antagonist naltrexone may improve smoking quit rates and reduce alcohol use in drinker–smokers, but its relative efficacy in smokers with a range of drinking patterns is unknown. The current study tested the hypothesis that HDS would show differential benefit of naltrexone versus placebo relative to moderate-to-light or nondrinking smokers in terms of improving smoking outcomes and reducing alcohol consumption.Methods Adult smokers (N = 315) enrolled in a 12-week, double-blinded, placebo-controlled trial of 50 mg naltrexone for smoking cessation were categorized into subgroups based upon past 6-month drinking patterns: HDS (n = 69; i.e., averaged ≥2 heavy drinking episodes per month), moderate-to-light drinking smokers (n = 204, i.e., consumed 1 drink up to a maximum of <2 heavy drinking episodes per month on average), or nondrinking smokers (n = 42, no alcohol consumed in the past 6 months). The groups were compared on the main study outcomes of biochemically verified prolonged abstinence quit rates (i.e., no smoking weeks 2 to 12), and smoking urge and alcohol use (drinks/wk) during treatment.ResultsNaltrexone significantly increased 12-week smoking abstinence rates and decreased smoking urge and alcohol use among HDS, but not moderate-to-light or nondrinking smokers. Mediation analyses in HDS revealed that naltrexone's effect on smoking urge during the first 4 weeks of treatment mediated its effect on quit rates.ConclusionsHDS appear to be particularly sensitive to naltrexone effects on smoking and drinking outcomes. This group may represent an important target for adjunctive treatment with naltrexone to optimize smoking cessation outcomes.
    Full-text · Article · Oct 2014 · Alcoholism Clinical and Experimental Research
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    • "The possibility of combining medications with brief motivational interventions for young adults warrants further investigation. Naltrexone, for example, may be well suited to this population because it can reduce drinking even in the absence of alcohol counseling (O'Malley et al. 2009; Tidey et al. 2008) and targeted administration of naltrexone in anticipation of high­ risk situations significantly reduced drinking among problem drinkers (Kranzler et al. 2009). A preliminary open­label study of naltrexone and BASICS in young adults suggests that this approach is associated with reductions in heavy drinking and alcohol­related consequences (Leeman et al. 2008). "
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    ABSTRACT: The prevalence of unidentified or untreated unhealthy alcohol use remains high. With the advent of pharmacotherapy and models of counseling appropriate for use in primary care settings as well as in specialty care, clinicians have new tools to manage the range of alcohol problems across the spectrum of health care settings. By extending treatment to primary care, many people who do not currently receive specialty care may have increased access to treatment. In addition, primary care providers, by virtue of their ongoing relationship with patients, may be able to provide continuing treatment over time. Extending the spectrum of care to hazardous drinkers who may not be alcohol dependent could result in earlier intervention and reduce the consequences of excessive drinking.
    Full-text · Article · Mar 2011 · Alcohol research & health: the journal of the National Institute on Alcohol Abuse and Alcoholism
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    • " versus nausea experi - enced when drinking alcohol . Future research is warranted to examine these potential mechanisms in more detail . The naltrexone - induced decreases in alcohol drinking , par - ticularly heavy drinking , observed in this study replicate and extend findings from another recent trial with naltrexone in smoking cessation ( O ' Malley et al . , 2008 ) . In the study by O ' Malley and colleagues ( 2008 ) , participants received less intensive and briefer smoking cessation counseling ( 15 min weekly with a bachelor ' s level research assistant ) and results showed that either 25 or 50 mg oral daily naltrexone , but not 100 mg , increased time to remission to daily hazardous drink - i"
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    ABSTRACT: There is mixed support for the efficacy of the opioid antagonist naltrexone in the treatment of nicotine dependence. One potential unexplored mechanism underlying naltrexone's effects in smoking cessation may be in its ability to reduce alcohol consumption. Alcohol consumption and liver enzyme levels (aspartate aminotransferase and alanine transaminase) were examined in a sample of 78 nonalcoholic social drinking smokers (34 naltrexone, 44 placebo) enrolled in a double-blind randomized clinical trial of naltrexone in smoking cessation. Naltrexone or placebo began 3 days prior to the quit date (25 mg daily) and continued for 8 weeks (50 mg daily). All participants received nicotine patches and behavioral counseling up through 4 weeks after the quit date. Naltrexone significantly reduced weekly heavy drinking rates. This effect was associated with greater nausea and pill taking adherence within the naltrexone group. Within heavy drinkers, naltrexone also directionally improved smoking quit rates compared with placebo. Liver enzyme levels did not differ during treatment with naltrexone compared with placebo. Naltrexone may reduce the frequency of heavy drinking in nonalcoholics attempting to quit smoking. Further, naltrexone may preferentially improve smoking quit rates within heavy drinkers who smoke, and further investigation in larger sample sizes is warranted.
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