The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. Smokers report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking.To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone.We searched the Cochrane Tobacco Addiction Group trials register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of Medline using '"Narcotic antagonists" and smoking terms in March 2001. We also contacted, when possible, investigators for information on unpublished studies.We considered randomized controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included only trials reporting data on abstinence of a minimum of 6 months in the meta-analyses. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psychobiological mediating variables associated with nicotine dependence.We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was cotinine or carbon monoxide verified abstinence from smoking after at least six months follow-up in patients smoking at baseline. Where appropriate, we performed meta-analysis using a fixed effects model (Peto method).Two trials of naltrexone met inclusion criteria for meta-analyses for long term cessation. Both trials failed to detect a significant difference in quit rates between naltrexone and placebo. In a pooled analysis there was no significant effect of naltrexone on long-term abstinence, and confidence intervals were wide (OR 1.34, 95% CI 0.49,3.63). No trials of naloxone or buprenorphine reported long term follow-upBased on limited data from two trials it is not possible to confirm or refute whether naltrexone helps smokers quit. The confidence intervals are compatible with both clinically significant benefit and possible negative effects of naltrexone in promoting abstinence. Data from larger trials of naltrexone are needed to settle the question of efficacy for smoking cessation.
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