尼古丁受体部分激动剂在戒烟中的作用
2011/03/23
摘要
背景：尼古丁受体部分激动剂能帮助吸烟者戒烟，这可能与其能维持中等水平的多巴胺来对抗戒断症状（作为激动剂产生作用）及降低吸烟吸烟欲望（作为拮抗剂产生作用）有关。伐尼克兰为来自于金雀花碱的尼古丁受体部分激动剂，而金雀花碱已经在西欧广泛的用于戒烟。2006年首次报道伐尼克兰在戒烟中的运用，对于其戒烟疗效已有进一步的报道，还有一些试验还正在进行。
目的：本综述旨在评价尼古丁受体部分激动剂（包括伐尼克兰和金雀花碱）用于戒烟的疗效和耐受性。
检索策略：对Cochrane烟草成瘾组织登记的试验进行检索，检索出现在题目、摘要或关键词中的有关“伐尼克兰”、“金雀花碱”、“Tabex”、“尼古丁受体部分激动剂”和吸烟的试验。同时，采用MeSH主题词和自由词，检索MEDLINE, EMBASE, PsycINFO和CINAHL数据库。必要时联系试验的作者，获取额外信息。
选择标准：选择的研究为比较治疗药物和安慰剂的随机对照试验。此外，有关安非他酮与尼古丁贴剂的研究也入选进行分析。排除那些最小随访期不超过6个月的研究。
数据收集和分析：提取参与者类型、治疗的剂量和疗程、所检测的疗效指标、随机过程、盲法分组和是否完成随访等信息。检测的主要疗效指标为治疗至少6个月后的戒断情况。我们采用了戒断最为严格的定义、生化法证实的戒断率。适当时候，采用Mantel-Haenszel固定效应模型进行荟萃分析，得出风险比。
主要结果：共有11项试验研究了伐尼克兰和安慰剂在戒烟中的作用，其中3项研究含有安非他酮试验组。另有1项试验研究伐尼克兰和安慰剂在预防复吸中的作用，2项开放标记试验比较了伐尼克兰和尼古丁替代治疗在戒烟中的作用。此外，在1项试验中，所有受试者均接受伐尼克兰治疗，但不同的吸烟者接受在线、电话或同时两种行为支持疗法。该试验未纳入后续的分析，但数据作为安全性和耐受性的一部分。纳入的试验总计入选>10300名参与者，其中6892名参与者采用伐尼克兰治疗。其中一项试验研究金雀花碱(Tabex)。在采用伐尼克兰标准剂量和安慰剂戒烟时，6个月或更长时间的持续戒断汇总风险比（RR）（来自10个试验、4443名受试者，排除一项研究长期安全性的试验）为2.31 (95%CI：2.01～2.66)。伐尼克兰在较低剂量及其他剂量同样显示能有效戒烟（RR, 2.09；95%CI 1.56～2.78；4个试验，1272名受试者）。伐尼克兰与安非他酮相比，用于戒烟1年的汇总RR为1.52 (95% CI 1.22～1.88; 3个试验, 1622名受试者)。伐尼克兰与NRT相比，在24周的点戒断率RR为1.13 (95% CI 0.94～1.35; 2个试验, 778名受试者)。另有2项试验研究伐尼克兰在戒烟中作用，采用标准方案，疗程超过12周，结果显示，该药长期使用的耐受性较好。伐尼克兰的主要副作用是恶心，一般为轻度至中度水平，随着时间延长逐渐缓解。有关上市后的安全性，主要是伐尼克兰可能与抑郁情绪、烦躁不安、自杀行为或自杀观念形成等有关。伐尼克兰的说明书在2008年进行了修订，厂商也向吸烟者提供了用药指南。目前为止，监测报告和对试验结果的二级分析尚未证实上述相关性。本综述入选的1项金雀花碱试验结果显示，采用金雀花碱戒烟的吸烟者，在2年的随访期内，与安慰剂相比，更多的吸烟者会达到戒烟，其RR为1.61 (95% CI 1.24～2.08)。
作者结论：伐尼克兰标准剂量，能增加长期成功戒烟的几率，其有效性是对照组的2～3倍。低剂量的伐尼克兰也有助于戒烟，而且降低了副作用。与安非他酮戒烟相比，更多的吸烟者采用伐尼克兰获得成功戒烟。2项开放标记的、研究伐尼克兰和NRT的试验显示，伐尼克兰戒烟的疗效中等，但可信区间并不排除两者等效。有限的证据显示，伐尼克兰可能有助于预防复吸。伐尼克兰的主要副作用是恶心，但大部分为轻度至中度，而且随着时间延长逐渐缓解。有关伐尼克兰严重副作用（包括抑郁情绪、烦躁不安和自杀想法）已有所报道，但尚未得到证实。有必要进行独立的、基于社区的伐尼克兰试验，研究其在不同共患病及危险因素的吸烟者中的戒烟疗效及安全性。此外，尚需进行药物长期戒烟（超过12周）疗效的研究。金雀花碱能增加戒烟的几率，但目前尚未有定论。
（林江涛 审校）
Cochrane Database Syst Rev. 2010 Dec 8;12: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.
Abstract
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 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 September 2010.
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 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 11 trials of varenicline compared with placebo for smoking cessation; three of these included a bupropion experimental arm. We also found one relapse prevention trial, comparing varenicline with placebo, and two open-label trials comparing varenicline with nicotine replacement therapy (NRT). We also include one trial in which all the participants were given varenicline, but received behavioural support either online or by phone calls, or by both methods. This trial is not included in the analyses, but contributes to the data on safety and tolerability. The included studies covered >10,300 participants, 6892 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion.The pooled risk ratio (RR) (10 trials, 4443 people, excluding one trial evaluating long term safety) for continuous abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.31 (95% confidence interval [CI] 2.01 to 2.66). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.09 (95% CI 1.56 to 2.78; 4 trials, 1272 people). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88; 3 trials, 1622 people). The RR for varenicline versus NRT for point prevalence abstinence at 24 weeks was 1.13 (95% CI 0.94 to 1.35; 2 trials, 778 people). 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 raised questions about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline was amended in 2008, and the manufacturers produced a Medication Guide. Thus far, surveillance reports and secondary analyses of trial data lend little support to a causal relationship.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 at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. 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, have been reported but are so far not substantiated. There is a need for further 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.
Cochrane Database Syst Rev. 2010 Dec 8;12:CD006103.
背景：尼古丁受体部分激动剂能帮助吸烟者戒烟，这可能与其能维持中等水平的多巴胺来对抗戒断症状（作为激动剂产生作用）及降低吸烟吸烟欲望（作为拮抗剂产生作用）有关。伐尼克兰为来自于金雀花碱的尼古丁受体部分激动剂，而金雀花碱已经在西欧广泛的用于戒烟。2006年首次报道伐尼克兰在戒烟中的运用，对于其戒烟疗效已有进一步的报道，还有一些试验还正在进行。
目的：本综述旨在评价尼古丁受体部分激动剂（包括伐尼克兰和金雀花碱）用于戒烟的疗效和耐受性。
检索策略：对Cochrane烟草成瘾组织登记的试验进行检索，检索出现在题目、摘要或关键词中的有关“伐尼克兰”、“金雀花碱”、“Tabex”、“尼古丁受体部分激动剂”和吸烟的试验。同时，采用MeSH主题词和自由词，检索MEDLINE, EMBASE, PsycINFO和CINAHL数据库。必要时联系试验的作者，获取额外信息。
选择标准：选择的研究为比较治疗药物和安慰剂的随机对照试验。此外，有关安非他酮与尼古丁贴剂的研究也入选进行分析。排除那些最小随访期不超过6个月的研究。
数据收集和分析：提取参与者类型、治疗的剂量和疗程、所检测的疗效指标、随机过程、盲法分组和是否完成随访等信息。检测的主要疗效指标为治疗至少6个月后的戒断情况。我们采用了戒断最为严格的定义、生化法证实的戒断率。适当时候，采用Mantel-Haenszel固定效应模型进行荟萃分析，得出风险比。
主要结果：共有11项试验研究了伐尼克兰和安慰剂在戒烟中的作用，其中3项研究含有安非他酮试验组。另有1项试验研究伐尼克兰和安慰剂在预防复吸中的作用，2项开放标记试验比较了伐尼克兰和尼古丁替代治疗在戒烟中的作用。此外，在1项试验中，所有受试者均接受伐尼克兰治疗，但不同的吸烟者接受在线、电话或同时两种行为支持疗法。该试验未纳入后续的分析，但数据作为安全性和耐受性的一部分。纳入的试验总计入选>10300名参与者，其中6892名参与者采用伐尼克兰治疗。其中一项试验研究金雀花碱(Tabex)。在采用伐尼克兰标准剂量和安慰剂戒烟时，6个月或更长时间的持续戒断汇总风险比（RR）（来自10个试验、4443名受试者，排除一项研究长期安全性的试验）为2.31 (95%CI：2.01～2.66)。伐尼克兰在较低剂量及其他剂量同样显示能有效戒烟（RR, 2.09；95%CI 1.56～2.78；4个试验，1272名受试者）。伐尼克兰与安非他酮相比，用于戒烟1年的汇总RR为1.52 (95% CI 1.22～1.88; 3个试验, 1622名受试者)。伐尼克兰与NRT相比，在24周的点戒断率RR为1.13 (95% CI 0.94～1.35; 2个试验, 778名受试者)。另有2项试验研究伐尼克兰在戒烟中作用，采用标准方案，疗程超过12周，结果显示，该药长期使用的耐受性较好。伐尼克兰的主要副作用是恶心，一般为轻度至中度水平，随着时间延长逐渐缓解。有关上市后的安全性，主要是伐尼克兰可能与抑郁情绪、烦躁不安、自杀行为或自杀观念形成等有关。伐尼克兰的说明书在2008年进行了修订，厂商也向吸烟者提供了用药指南。目前为止，监测报告和对试验结果的二级分析尚未证实上述相关性。本综述入选的1项金雀花碱试验结果显示，采用金雀花碱戒烟的吸烟者，在2年的随访期内，与安慰剂相比，更多的吸烟者会达到戒烟，其RR为1.61 (95% CI 1.24～2.08)。
作者结论：伐尼克兰标准剂量，能增加长期成功戒烟的几率，其有效性是对照组的2～3倍。低剂量的伐尼克兰也有助于戒烟，而且降低了副作用。与安非他酮戒烟相比，更多的吸烟者采用伐尼克兰获得成功戒烟。2项开放标记的、研究伐尼克兰和NRT的试验显示，伐尼克兰戒烟的疗效中等，但可信区间并不排除两者等效。有限的证据显示，伐尼克兰可能有助于预防复吸。伐尼克兰的主要副作用是恶心，但大部分为轻度至中度，而且随着时间延长逐渐缓解。有关伐尼克兰严重副作用（包括抑郁情绪、烦躁不安和自杀想法）已有所报道，但尚未得到证实。有必要进行独立的、基于社区的伐尼克兰试验，研究其在不同共患病及危险因素的吸烟者中的戒烟疗效及安全性。此外，尚需进行药物长期戒烟（超过12周）疗效的研究。金雀花碱能增加戒烟的几率，但目前尚未有定论。
（林江涛 审校）
Cochrane Database Syst Rev. 2010 Dec 8;12: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.
Abstract
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 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 September 2010.
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 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 11 trials of varenicline compared with placebo for smoking cessation; three of these included a bupropion experimental arm. We also found one relapse prevention trial, comparing varenicline with placebo, and two open-label trials comparing varenicline with nicotine replacement therapy (NRT). We also include one trial in which all the participants were given varenicline, but received behavioural support either online or by phone calls, or by both methods. This trial is not included in the analyses, but contributes to the data on safety and tolerability. The included studies covered >10,300 participants, 6892 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion.The pooled risk ratio (RR) (10 trials, 4443 people, excluding one trial evaluating long term safety) for continuous abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.31 (95% confidence interval [CI] 2.01 to 2.66). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.09 (95% CI 1.56 to 2.78; 4 trials, 1272 people). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88; 3 trials, 1622 people). The RR for varenicline versus NRT for point prevalence abstinence at 24 weeks was 1.13 (95% CI 0.94 to 1.35; 2 trials, 778 people). 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 raised questions about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline was amended in 2008, and the manufacturers produced a Medication Guide. Thus far, surveillance reports and secondary analyses of trial data lend little support to a causal relationship.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 at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. 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, have been reported but are so far not substantiated. There is a need for further 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.
Cochrane Database Syst Rev. 2010 Dec 8;12:CD006103.
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吸烟和戒烟对脂质和脂蛋白的影响：来自随机临床试验的结果
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