尼古丁受体部分激动剂用于戒烟
2009/07/30
目的：首要目的是评价尼古丁受体部分激动剂（伐尼克兰，野靛碱）用于戒烟的有效性和耐受性。
检索策略：我们搜索烟草成瘾实验协作网为实验的专门登记表，在标题或摘要或关键词中用一下的词条(‘varenicline’ or ‘cytisine’ or ’Tabex’ or ’nicotine receptor partial agonist’) and ’smoking’来检索。我们也用主题词和自由正文检索MEDLINE, EMBASE, PsycINFO and CINAHL，当有必要的时候我们还会联系实验报告的作者以获得额外的信息。最晚的检索时间是2008年3月。
入选标准：治疗组对安慰剂组的RCT实验，也入选与尼古丁和安非他酮比较的实验，剔除最短随访时间不到6个月的实验。主要的结果测量是戒烟从治疗开始至少随访6个月。对于每个实验我们要求最严格的戒烟的定义，生物化学验证。用Mantel-Haenszel固定效应模型做Meta-分析得出危险比。
主要结果：发现7个伐尼克兰对安慰剂的戒烟实验，其中三个是包括安菲他酮，一个是伐尼克兰对安慰剂防止复吸的实验，一个伐尼克兰对安菲他酮和尼古丁替代的非盲试验。这就个实验受试者共有7267名，其中4744名服用伐尼克兰，发现一个实验内含金雀花碱。持续戒烟时间大于等于6个月的伐尼克兰对安慰剂的RR值为2.33 (95% CI：1.95 -2.80)。戒烟1年的伐尼克兰对安菲他酮的RR值为1.52 (95% CI 1.22 -1.88)。这两个实验显示12周的标准服药，长期用伐尼克兰耐受性良好。主要副作用为恶心大多为轻中度，往往会消失，市后的安全性数据表明，可能有与情绪低落，兴奋，有自杀的想法相关的副作用。伐尼克兰的标签已经修改了，FDA会做一安全性的回顾。一个为期2年的金雀花碱对安慰剂戒烟的实验其RR值为：1.61 (95% CI ：1.24 -2.08)。
结论：相比于没有接受药物帮助戒烟，伐尼克兰成功的机会要高2～3倍，用伐尼克兰戒烟获得成功的要比用安非他酮的要多，一个伐尼克兰对尼古丁替代疗法的非盲实验表明伐尼克兰有轻度的获益，伐尼克兰防止复吸还没有获得证实。主要的副作用是恶心，大多为轻中度，往往会消失，可能的严重副作用有：情绪低落，兴奋，有自杀的想法，当前在观察中，需要基于社会的有关伐尼克兰的独立实验来考察它的安全性和有效性。对有不同并发症的烟民和危险性需要有治疗超过12周的有效性试验。野靛碱也可以增加戒烟成功的机会，但当前的证据是非决定性的。
（刘超武编译 刘国梁审校）
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006103
Update of: Cochrane Database Syst Rev. 2007;(1):CD006103
Nicotine receptor partial agonists for smoking cessation.
Cahill K, Stead LF, Lancaster T.
Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Oxford, UK, OX3 7LF. kate.cahill@dphpc.ox.ac.uk
BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Varenicline was developed as a nicotine receptor partial agonist from cytisine, a drug widely used in central and eastern Europe for smoking cessation. The first trial reports of varenicline were released in 2006, and further trials have now been published or are currently are underway.
OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.
SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group’s specialised register for trials, using the terms (’varenicline’ or ’cytisine’ or ’Tabex’ or ’nicotine receptor partial agonist’) and ’smoking’ in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL using MeSH terms and free text, and we contacted authors of trial reports for additional information where necessary. The latest search was in March 2008.
SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment.
DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow up.The main outcome measured was abstinence from smoking after at least six months from the beginning of treatment. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we performed meta-analysis to produce a risk ratio, using the Mantel-Haenszel fixed-effect model.
MAIN RESULTS: We found seven trials of varenicline compared with placebo for smoking cessation; three of these also included a bupropion experimental arm. We found one relapse prevention trial, comparing varenicline with placebo. We also found one open-label trial comparing varenicline with nicotine replacement therapy. The nine trials covered 7267 participants, 4744 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion.The pooled risk ratio (RR) for continuous abstinence at six months or longer for varenicline versus placebo was 2.33 (95% confidence interval [CI] 1.95 to 2.80). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88). The RR for varenicline versus NRT at one year was 1.31 (95% CI 1.01 to 1.71). The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Post-marketing safety data suggest that varenicline may be associated with depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline has been amended, and the FDA is conducting a safety review.The one cytisine trial included in this review found that more participants taking cytisine stopped smoking compared with placebo at two-year follow up, with an RR of 1.61 (95% CI 1.24 to 2.08).
AUTHORS’ CONCLUSIONS: Varenicline increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. More participants quit successfully with varenicline than with bupropion. One open-label trial of varenicline versus nicotine replacement therapy demonstrated a modest benefit of varenicline. The effectiveness of varenicline as an aid to relapse prevention has not been clearly established. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including depressed mood, agitation and suicidal thoughts, are currently under review.There is a need for independent community-based trials of varenicline, to test its efficacy and safety in smokers with varying co-morbidities and risk patterns. There is a need for further trials of the efficacy of treatment extended beyond 12 weeks. Cytisine may also increase the chances of quitting, but the evidence at present is inconclusive.
PMID: 18646137 [PubMed - indexed for MEDLINE]
PMID: 18646137 [PubMed - indexed for MEDLINE]
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抗焦虑药和抗抑郁剂用于戒烟
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伐尼克兰联合尼古丁替代治疗
