1型大麻素受体拮抗剂在戒烟中的作用
2011/05/10
摘要
背景：选择1型大麻素(CB1)受体拮抗剂能通过恢复内源性大麻系统平衡来帮助戒烟，而内源性大麻系统紊乱主要由长期使用尼古丁所导致。而且一些研究显示，由于戒烟会导致体重增加，因此也打消了一些吸烟者戒烟的念头。
目的：研究选择性CB1受体拮抗剂（目前主要是利莫那班和泰伦那班）是否能增加吸烟者的戒烟率，评价这些药物对成功戒烟者以及有戒烟意愿但戒烟失败的吸烟者体重的影响。
检索策略：我们采用利莫那班、泰伦那班和吸烟为主题词或关键词，检索标题和摘要出现这些主题词的、Cochrane烟草成瘾审查小组注册的试验。同时，采用主要MESH主题词，对MEDLINE, EMBASE, CINAHL 和PsycINFO数据库进行检索。此外，还获取美国胸科学会2005年会议及欧洲尼古丁及烟草研究协会2006年会议的电子版或纸质版中初步研究。我们还试图联系正在进行的利莫那班研究的作者和赛诺菲安万特制药公司（利莫那班厂商）。最近1次检索是在2011年1月。
选择标准：研究类型：随机对照研究；参与者：成人吸烟者；干预措施：选择性CB1受体拮抗剂（如：利莫那班、泰伦那班）；检测指标：主要转归是开始治疗后至少6个月时的吸烟状态。我们优先采用持续戒断率，而不是点戒断率，优先采用生物化学方法确定的戒烟，而不是自我主诉的戒烟。将那些退出研究或失访的受试者定为持续吸烟者。记录任何治疗副作用。次要转归为与戒烟相关的体重变化。
数据收集和分析：两名作者对摘要的相关性进行审查，并试图获取完整的研究报告。一名作者提取数据，另一名作者对数据复查。
主要结果：共找到3项试验符合入选标准，共计1567名吸烟者（戒烟研究：STRATUS-EU和STRATUS-US）和1661名戒烟者（复吸预防：STRATUS-WW）。在第1年，利莫那班20 mg戒烟的汇总危险比（RR）为1.50 （95% CI：1.10 to 2.05）。利莫那班5 mg 对戒烟没有帮助。治疗的副作用主要有恶心、上呼吸道感染。在复吸预防试验中，与安慰剂相比，20 mg方案进行戒烟的吸烟者，在治疗期间更易维持戒断；20 mg 维持治疗组的RR为1.29 (95% CI 1.06～1.57)，5 mg维持治疗组的RR为1.30 (95% CI：1.06～1.59)。5 mg 维持治疗对戒烟无明显作用。一项有关泰伦那班的试验未纳入此项荟萃分析，因为该研究随访在治疗结束就终止，在为期8周的治疗后，与安慰剂组相比，对戒烟无帮助，OR 为1.2 (90% CI 0.6～2.5)。与安慰剂和5 mg利莫那班治疗的戒烟者相比，利莫那班20 mg治疗后的戒烟者其体重增加显著下降。治疗期间，超重或肥胖吸烟体重有下降趋势，但正常体重吸烟者无该趋势。与安慰剂相比，在为期8周泰伦那班2-8 mg治疗结束后体重增加显著降低。2008年上市后的调查，导致欧洲药品局(EMEA)要求赛诺菲安万特制药公司召回利莫那班，因为利莫那班有导致精神疾病的可能。默克公司公司对泰伦那班的开发也陷入停滞状态，因为出现了不能接受的副作用。
作者结论：基于报道的临床研究，利莫那班能使戒烟的机会增加1.5倍。对于利莫那班是否能维持戒断尚无定论。长期治疗来说，利莫那班20 mg仅使体重中度增加。泰伦那班2-8 mg至少在短期可使体重中度增加。自2008年开始，制药商对利莫那班和泰伦那班开发已经陷入停滞。
（刘国梁 审校）
Cochrane Database Syst Rev. 2011 Mar 16;3:CD005353.
Cannabinoid type 1 receptor antagonists for smoking cessation.
Cahill K, Ussher MH.
Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Oxford, UK, OX3 7LF.
Abstract
BACKGROUND: Selective type 1 cannabinoid (CB1) receptor antagonists may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. They also seeks to address many smokers’ reluctance to persist with a quit attempt because of concerns about weight gain.
OBJECTIVES: To determine whether selective CB1 receptor antagonists (currently rimonabant and taranabant) increase the numbers of people stopping smoking To assess their effects on weight change in successful quitters and in those who try to quit but fail.
SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms (’rimonabant’ or ’taranabant’) and ’smoking’ in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis (manufacturers of rimonabant). The most recent search was in January 2011.
SELECTION CRITERIA: Types of studies Randomized controlled trials Types of participants Adult smokers Types of interventions Selective CB1 receptor antagonists, such as rimonabant and taranabant. Types of outcome measures The primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self-reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment.A secondary outcome is weight change associated with the cessation attempt.
DATA COLLECTION AND ANALYSIS: Two authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them.
MAIN RESULTS: We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661 quitters (relapse prevention: STRATUS-WW). At one year, the pooled risk ratio (RR) for quitting with rimonabant 20 mg was 1.50 (95% confidence interval (CI) 1.10 to 2.05). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections. In the relapse prevention trial, smokers who had quit on the 20 mg regimen were more likely to remain abstinent on either active regimen than on placebo; the RR for the 20 mg maintenance group was 1.29 (95% CI 1.06 to 1.57), and for the 5 mg maintenance group 1.30 (95% CI 1.06 to 1.59). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters. One trial of taranabant was not included in our meta-analyses, as it followed participants only until end of treatment; at eight weeks it found no benefit for treatment over placebo, with an OR of 1.2 (90% CI 0.6 to 2.5). For rimonabant, weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not. For taranabant, weight gain was significantly lower for 2-8 mg versus placebo at the end of eight weeks of treatment. In 2008, post-marketing surveillance led the European Medicines Agency (EMEA) to require Sanofi Aventis to withdraw rimonabant, because of links to mental disorders. The development of taranabant was also suspended by Merck & Co because of unacceptable adverse events.
AUTHORS’ CONCLUSIONS: From the trial reports available, rimonabant 20 mg may increase the chances of quitting approximately 1½-fold. The evidence for rimonabant in maintaining abstinence is inconclusive. Rimonabant 20 mg may moderate weight gain in the long term. Taranabant 2-8 mg may moderate weight gain, at least in the short term. In 2008, development of both rimonabant and taranabant was discontinued by the manufacturers.
Cochrane Database Syst Rev. 2011 Mar 16;3:CD005353.
背景：选择1型大麻素(CB1)受体拮抗剂能通过恢复内源性大麻系统平衡来帮助戒烟，而内源性大麻系统紊乱主要由长期使用尼古丁所导致。而且一些研究显示，由于戒烟会导致体重增加，因此也打消了一些吸烟者戒烟的念头。
目的：研究选择性CB1受体拮抗剂（目前主要是利莫那班和泰伦那班）是否能增加吸烟者的戒烟率，评价这些药物对成功戒烟者以及有戒烟意愿但戒烟失败的吸烟者体重的影响。
检索策略：我们采用利莫那班、泰伦那班和吸烟为主题词或关键词，检索标题和摘要出现这些主题词的、Cochrane烟草成瘾审查小组注册的试验。同时，采用主要MESH主题词，对MEDLINE, EMBASE, CINAHL 和PsycINFO数据库进行检索。此外，还获取美国胸科学会2005年会议及欧洲尼古丁及烟草研究协会2006年会议的电子版或纸质版中初步研究。我们还试图联系正在进行的利莫那班研究的作者和赛诺菲安万特制药公司（利莫那班厂商）。最近1次检索是在2011年1月。
选择标准：研究类型：随机对照研究；参与者：成人吸烟者；干预措施：选择性CB1受体拮抗剂（如：利莫那班、泰伦那班）；检测指标：主要转归是开始治疗后至少6个月时的吸烟状态。我们优先采用持续戒断率，而不是点戒断率，优先采用生物化学方法确定的戒烟，而不是自我主诉的戒烟。将那些退出研究或失访的受试者定为持续吸烟者。记录任何治疗副作用。次要转归为与戒烟相关的体重变化。
数据收集和分析：两名作者对摘要的相关性进行审查，并试图获取完整的研究报告。一名作者提取数据，另一名作者对数据复查。
主要结果：共找到3项试验符合入选标准，共计1567名吸烟者（戒烟研究：STRATUS-EU和STRATUS-US）和1661名戒烟者（复吸预防：STRATUS-WW）。在第1年，利莫那班20 mg戒烟的汇总危险比（RR）为1.50 （95% CI：1.10 to 2.05）。利莫那班5 mg 对戒烟没有帮助。治疗的副作用主要有恶心、上呼吸道感染。在复吸预防试验中，与安慰剂相比，20 mg方案进行戒烟的吸烟者，在治疗期间更易维持戒断；20 mg 维持治疗组的RR为1.29 (95% CI 1.06～1.57)，5 mg维持治疗组的RR为1.30 (95% CI：1.06～1.59)。5 mg 维持治疗对戒烟无明显作用。一项有关泰伦那班的试验未纳入此项荟萃分析，因为该研究随访在治疗结束就终止，在为期8周的治疗后，与安慰剂组相比，对戒烟无帮助，OR 为1.2 (90% CI 0.6～2.5)。与安慰剂和5 mg利莫那班治疗的戒烟者相比，利莫那班20 mg治疗后的戒烟者其体重增加显著下降。治疗期间，超重或肥胖吸烟体重有下降趋势，但正常体重吸烟者无该趋势。与安慰剂相比，在为期8周泰伦那班2-8 mg治疗结束后体重增加显著降低。2008年上市后的调查，导致欧洲药品局(EMEA)要求赛诺菲安万特制药公司召回利莫那班，因为利莫那班有导致精神疾病的可能。默克公司公司对泰伦那班的开发也陷入停滞状态，因为出现了不能接受的副作用。
作者结论：基于报道的临床研究，利莫那班能使戒烟的机会增加1.5倍。对于利莫那班是否能维持戒断尚无定论。长期治疗来说，利莫那班20 mg仅使体重中度增加。泰伦那班2-8 mg至少在短期可使体重中度增加。自2008年开始，制药商对利莫那班和泰伦那班开发已经陷入停滞。
（刘国梁 审校）
Cochrane Database Syst Rev. 2011 Mar 16;3:CD005353.
Cannabinoid type 1 receptor antagonists for smoking cessation.
Cahill K, Ussher MH.
Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Oxford, UK, OX3 7LF.
Abstract
BACKGROUND: Selective type 1 cannabinoid (CB1) receptor antagonists may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. They also seeks to address many smokers’ reluctance to persist with a quit attempt because of concerns about weight gain.
OBJECTIVES: To determine whether selective CB1 receptor antagonists (currently rimonabant and taranabant) increase the numbers of people stopping smoking To assess their effects on weight change in successful quitters and in those who try to quit but fail.
SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms (’rimonabant’ or ’taranabant’) and ’smoking’ in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis (manufacturers of rimonabant). The most recent search was in January 2011.
SELECTION CRITERIA: Types of studies Randomized controlled trials Types of participants Adult smokers Types of interventions Selective CB1 receptor antagonists, such as rimonabant and taranabant. Types of outcome measures The primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self-reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment.A secondary outcome is weight change associated with the cessation attempt.
DATA COLLECTION AND ANALYSIS: Two authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them.
MAIN RESULTS: We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661 quitters (relapse prevention: STRATUS-WW). At one year, the pooled risk ratio (RR) for quitting with rimonabant 20 mg was 1.50 (95% confidence interval (CI) 1.10 to 2.05). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections. In the relapse prevention trial, smokers who had quit on the 20 mg regimen were more likely to remain abstinent on either active regimen than on placebo; the RR for the 20 mg maintenance group was 1.29 (95% CI 1.06 to 1.57), and for the 5 mg maintenance group 1.30 (95% CI 1.06 to 1.59). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters. One trial of taranabant was not included in our meta-analyses, as it followed participants only until end of treatment; at eight weeks it found no benefit for treatment over placebo, with an OR of 1.2 (90% CI 0.6 to 2.5). For rimonabant, weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not. For taranabant, weight gain was significantly lower for 2-8 mg versus placebo at the end of eight weeks of treatment. In 2008, post-marketing surveillance led the European Medicines Agency (EMEA) to require Sanofi Aventis to withdraw rimonabant, because of links to mental disorders. The development of taranabant was also suspended by Merck & Co because of unacceptable adverse events.
AUTHORS’ CONCLUSIONS: From the trial reports available, rimonabant 20 mg may increase the chances of quitting approximately 1½-fold. The evidence for rimonabant in maintaining abstinence is inconclusive. Rimonabant 20 mg may moderate weight gain in the long term. Taranabant 2-8 mg may moderate weight gain, at least in the short term. In 2008, development of both rimonabant and taranabant was discontinued by the manufacturers.
Cochrane Database Syst Rev. 2011 Mar 16;3:CD005353.
