Nicotine receptor partial agonists for smoking cessation
Nicotine receptor partial agonists for smoking cessation
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DOI：
10.1002/14651858.cd006103.pub6
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发表时间：
2012-01-01
影响因子：
1.4
通讯作者：
Polonio, Igor Bastos
中科院分区：
文献类型：
--
作者：
Cahill, Kate;Stead, Lindsay F.;Polonio, Igor Bastos
背景吸烟是全世界疾病和过早死亡的主要可预防原因。一些药物已被证明可以帮助人们戒烟，其中三种药物在欧洲和美国获得了用于此目的的许可：尼古丁替代疗法 (NRT)、安非他酮和伐尼克兰。金雀花碱（一种药理学上与伐尼克兰相似的治疗方法）也获准在俄罗斯和一些前社会主义经济国家使用。包括去甲替林在内的其他疗法也经过了有效性测试。目的NRT、安非他酮和伐尼克兰与安慰剂以及彼此之间在实现长期戒断（六个月或更长时间）方面如何比较？其余治疗与安慰剂在实现长期戒断方面如何比较？治疗之间不良和严重不良事件 (SAE) 的风险如何比较，是否存在弊大于利的情况？方法概述仅限于Cochrane 评论，所有这些评论都包含随机试验。参与者通常是成年吸烟者，但我们排除了针对孕妇以及特定疾病群体或特定环境的戒烟评论。我们承保尼古丁替代疗法 (NRT)、抗抑郁药（安非他酮和去甲替林）、尼古丁受体部分激动剂（伐尼克兰和金雀花碱）、抗焦虑药、选择性 1 型大麻素受体拮抗剂（利莫那班）、可乐定、洛贝林、达尼克兰、美加明、尼古丁、阿片类拮抗剂、尼古丁疫苗和醋酸银。我们的获益结果是从治疗开始后至少六个月持续或长期禁欲。我们的危害结果是与每种治疗相关的严重不良事件的发生率。我们在 Cochrane 图书馆的 Cochrane 系统评价数据库 (CDSR) 中搜索了标题、摘要或关键词字段中包含“吸烟”的任何评论。最后一次检索是在 2012 年 11 月进行的。我们使用修订版的 AMSTAR 量表评估了方法学质量。对于 NRT、安非他酮和伐尼克兰，我们进行了网络荟萃分析，将各自与其他药物以及与安慰剂的益处进行了比较，并比较了伐尼克兰和安非他酮的严重不良事件风险。主要结果我们确定了 12 项针对特定治疗的评价。分析涵盖 267 项研究，涉及 101,804 名参与者。 NRT 和安非他酮均优于安慰剂（比值比 (OR) 1.84；95% 可信区间 (CredI) 1.71 至 1.99，和 1.82；95% CredI 1.60 至 2.06）。与安慰剂相比，伐尼克兰增加了戒烟的几率（OR 2.88；95% CredI 2.40 至 3.47）。安非他酮和 NRT 之间的头对头比较显示出相同的疗效（OR 0.99；95% CredI 0.86 至 1.13）。伐尼克兰优于单一形式的 NRT（OR 1.57；95% CredI 1.29 至 1.91）和安非他酮（OR 1.59；95% CredI 1.29 至 1.13）。 1.96）。伐尼克兰比尼古丁贴片（OR 1.51；95% CredI 1.22 至 1.87）、尼古丁口香糖（OR 1.72；95% CredI 1.38 至 2.13）以及“其他”NRT（吸入器、喷雾剂、片剂、锭剂；OR 1.42；95% CredI 1.12 至 1.12）更有效。 1.79），但并不比联合 NRT 更有效（OR 1.06；95% CredI 0.75 至 1.48）。组合 NRT 的效果也优于单一制剂。除了“其他”NRT 比 NRT 口香糖稍微有效（OR 1.21；95% CredI 1.01 至 1.46）之外，这四类 NRT 的表现相似。金雀花碱（尼古丁受体部分激动剂）返回阳性结果（风险比 (RR) 3.98；95% CI 2.01 至 7.87），没有明显的不良事件或SAE。在 82 项纳入和排除的安非他酮试验中，我们估计安非他酮组有 6 次癫痫发作，而安慰剂组没有癫痫发作，低于预期发生率 (1:1000)，约为 1:1500。安非他酮研究的 SAE 荟萃分析表明，没有出现过多的神经精神事件（RR 0.88；95% CI 0.31 至 2.50）或心血管事件（RR 0.77；95% CI 0.37 至 1.59）。对 14 项伐尼克兰试验进行的 SAE 荟萃分析发现，伐尼克兰组和安慰剂组之间没有差异（RR 1.06；95% CI 0.72 至 1.55），亚组分析未发现神经精神事件（RR 0.53；95% CI 0.17 至 1.67）或心脏事件（RR 1.26；95% CI 0.62 至 1.67）显着增加。 2.56).去甲替林增加了戒烟的机会（RR 2.03；95% CI 1.48 至 2.78）。与单独使用 NRT 相比，去甲替林和安非他酮均未显示能增强 NRT 的效果。可乐定增加了戒烟的机会（RR 1.63；95% CI 1.22至2.18），但这被剂量依赖性的不良事件增加所抵消。美加明联合 NRT 可能会增加戒烟的机会，但目前的证据尚无定论。与安慰剂相比，其他治疗方法未能显示出益处。尼古丁疫苗尚未获得许可用于辅助戒烟或预防复吸。 Nicobrevin 的英国许可证现已被吊销，利莫那班、塔拉那班和达尼克林的制造商不再支持这些治疗方法的开发或测试。 作者的结论 NRT、安非他酮、伐尼克兰和金雀花碱已被证明可以提高戒烟机会。 NRT 和伐尼克兰的组合与戒烟辅助剂同样有效。去甲替林还可以提高戒烟的机会。根据目前的证据，所有治疗方法似乎都没有出现会减少其使用的不良事件的发生率。有必要对伐尼克兰的安全性以及金雀花碱作为有效且负担得起的治疗方法的潜力进行进一步的研究，但不需要对 NRT 的功效和安全性进行研究。
BackgroundSmoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness.ObjectivesHow do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)?How do the remaining treatments compare with placebo in achieving long-term abstinence?How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits?MethodsThe overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments.We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events.Main resultsWe identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectively). Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% CredI 2.40 to 3.47). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13).Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46).Cytisine (a nicotine receptor partial agonist) returned positive findings (risk ratio (RR) 3.98; 95% CI 2.01 to 7.87), without significant adverse events or SAEs.Across the 82 included and excluded bupropion trials, our estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1: 1000), at about 1: 1500. SAE meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59). SAE meta-analysis of 14 varenicline trials found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56).Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone. Clonidine increased the chances of quitting (RR 1.63; 95% CI 1.22 to 2.18), but this was offset by a dose-dependent rise in adverse events. Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive. Other treatments failed to demonstrate a benefit compared with placebo. Nicotine vaccines are not yet licensed for use as an aid to smoking cessation or relapse prevention. Nicobrevin's UK license is now revoked, and the manufacturers of rimonabant, taranabant and dianicline are no longer supporting the development or testing of these treatments.Authors' conclusionsNRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use.Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.