乙酰胆碱酯酶抑制剂多奈哌齐对未进行戒烟治疗吸烟者认知的影响：初步可行性研究
2012/07/05
摘要
背景：有必要寻找措施帮助戒烟。降低撤药相关的认知缺陷是新药开发时需关注的一个药理学靶点。内源性乙酰胆碱水平受到乙酰胆碱酯酶抑制剂（AChEI）的调节。乙酰胆碱水平在吸烟行为和认知中具有重要作用。此项初步可行性试验旨在研究AChEI多奈哌齐是否能改善健康吸烟者的认知能力。
方法：18名未接受治疗的每日吸烟者（6名女性）采用多奈哌齐（5mg q.d）或安慰剂治疗（双盲；2:1分配比例）4周。每周检测吸烟率、副作用和工作记忆的神经认知检测指标（Letter-N-back）和持续注意力（佩恩连续性能任务）。
结果：对于工作记忆任务，存在显著的组×负荷×时间交互作用（P=0.03），表明多奈哌齐组从基础状态到治疗4周后真阳性增加，具有最高的工作记忆负荷（3-back）。安慰剂组在准确性上无显著差异。对于持续注意力任务，对同一方向的辨别力上具有边缘效应，或者d’, P=0.08。对两个任务的反应时间无显著影响。安慰剂组在每日吸烟量上有所下降，该现象未在多奈哌齐组中观察到。
结论：健康吸烟者采用AChEI（如多奈哌齐）戒烟，对认知具有促进作用，但吸烟者仍然象往常一样吸烟。由于认知缺陷和复吸间存在相关性，AChEI可以作为吸烟的一个潜在治疗措施。
（陈欣 审校）
Drug Alcohol Depend. 2012 May 15. [Epub ahead of print]
Cognitive effects of the acetylcholinesterase inhibitor, donepezil, in healthy, non-treatment seeking smokers: A pilot feasibility study.
Ashare RL, Ray R, Lerman C, Strasser AA.
Source
University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA 19104, USA.
Abstract
BACKGROUND: There is a need to identify medications to aid in smoking cessation. Reducing withdrawal-related cognitive deficits represents a pharmacological target for new pharmacotherapies. Endogenous acetylcholine levels, which are modulated by acetylcholinesterase inhibitors (AChEIs), play an important role in smoking behavior and cognition. This pilot feasibility study tested whether an AChEI, donepezil, enhanced cognitive performance among healthy smokers.
METHODS: Eighteen non-treatment seeking daily smokers (6 female) received either donepezil (5mg q.d) or placebo (double-blind; 2:1 allocation ratio) for 4 weeks. Smoking rate, side effects, and neurocognitive measures of working memory (Letter-N-back) and sustained attention (Penn Continuous Performance Task) were assessed weekly.
RESULTS: For the working memory task, there was a significant group×load×time interaction (p=0.03) indicating that the donepezil group demonstrated an increase in true positives from baseline to week 4 at the highest working memory load (3-back). The placebo group showed no change in accuracy. For the sustained attention task, there was a marginal effect in the same direction for discriminability, or d’, p=0.08. There were no significant effects on reaction time during either task. There was also a reduction in cigarettes per day in the placebo group, but not the donepezil group.
CONCLUSIONS: AChEIs, such as donepezil, may have pro-cognitive effects among healthy smokers while they continue to smoke as usual. Given the association between cognitive deficits and relapse, AChEIs should be explored as potential therapeutics for smoking cessation
Drug Alcohol Depend. 2012 May 15. [Epub ahead of print]
背景：有必要寻找措施帮助戒烟。降低撤药相关的认知缺陷是新药开发时需关注的一个药理学靶点。内源性乙酰胆碱水平受到乙酰胆碱酯酶抑制剂（AChEI）的调节。乙酰胆碱水平在吸烟行为和认知中具有重要作用。此项初步可行性试验旨在研究AChEI多奈哌齐是否能改善健康吸烟者的认知能力。
方法：18名未接受治疗的每日吸烟者（6名女性）采用多奈哌齐（5mg q.d）或安慰剂治疗（双盲；2:1分配比例）4周。每周检测吸烟率、副作用和工作记忆的神经认知检测指标（Letter-N-back）和持续注意力（佩恩连续性能任务）。
结果：对于工作记忆任务，存在显著的组×负荷×时间交互作用（P=0.03），表明多奈哌齐组从基础状态到治疗4周后真阳性增加，具有最高的工作记忆负荷（3-back）。安慰剂组在准确性上无显著差异。对于持续注意力任务，对同一方向的辨别力上具有边缘效应，或者d’, P=0.08。对两个任务的反应时间无显著影响。安慰剂组在每日吸烟量上有所下降，该现象未在多奈哌齐组中观察到。
结论：健康吸烟者采用AChEI（如多奈哌齐）戒烟，对认知具有促进作用，但吸烟者仍然象往常一样吸烟。由于认知缺陷和复吸间存在相关性，AChEI可以作为吸烟的一个潜在治疗措施。
（陈欣 审校）
Drug Alcohol Depend. 2012 May 15. [Epub ahead of print]
Cognitive effects of the acetylcholinesterase inhibitor, donepezil, in healthy, non-treatment seeking smokers: A pilot feasibility study.
Ashare RL, Ray R, Lerman C, Strasser AA.
Source
University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA 19104, USA.
Abstract
BACKGROUND: There is a need to identify medications to aid in smoking cessation. Reducing withdrawal-related cognitive deficits represents a pharmacological target for new pharmacotherapies. Endogenous acetylcholine levels, which are modulated by acetylcholinesterase inhibitors (AChEIs), play an important role in smoking behavior and cognition. This pilot feasibility study tested whether an AChEI, donepezil, enhanced cognitive performance among healthy smokers.
METHODS: Eighteen non-treatment seeking daily smokers (6 female) received either donepezil (5mg q.d) or placebo (double-blind; 2:1 allocation ratio) for 4 weeks. Smoking rate, side effects, and neurocognitive measures of working memory (Letter-N-back) and sustained attention (Penn Continuous Performance Task) were assessed weekly.
RESULTS: For the working memory task, there was a significant group×load×time interaction (p=0.03) indicating that the donepezil group demonstrated an increase in true positives from baseline to week 4 at the highest working memory load (3-back). The placebo group showed no change in accuracy. For the sustained attention task, there was a marginal effect in the same direction for discriminability, or d’, p=0.08. There were no significant effects on reaction time during either task. There was also a reduction in cigarettes per day in the placebo group, but not the donepezil group.
CONCLUSIONS: AChEIs, such as donepezil, may have pro-cognitive effects among healthy smokers while they continue to smoke as usual. Given the association between cognitive deficits and relapse, AChEIs should be explored as potential therapeutics for smoking cessation
Drug Alcohol Depend. 2012 May 15. [Epub ahead of print]
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戒烟治疗的疗效：来自国际烟草控制组织（ITC）对4个国家的调查
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缓释安非他酮用于中国吸烟者戒烟：双盲、安慰剂对照、随机临床试验
