Clinical and Research Institute on Addictions, University at Buffalo-The State University of New York, Buffalo, New York, USA.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Addict Biol. 2022 Sep;27(5):e13218. doi: 10.1111/adb.13218.
Human laboratory studies are widely used to evaluate behavioural mechanisms of pharmacotherapy effects. Results from human laboratory studies examining smoking cessation pharmacotherapies have not been examined in aggregate. The current meta-analysis aimed to synthesize data from randomized, placebo-controlled human laboratory studies on the effects of non-nicotine pharmacotherapies on outcomes relevant for smoking cessation. Literature searches identified 15 human laboratory studies of varenicline (n = 697) and 9 studies of bupropion (n = 313) with sufficient data for inclusion. Studies involved acute or subacute pharmacotherapy treatment with administration durations ranging from a single dose to 8 weeks. Primary outcomes examined were craving, withdrawal and behavioural indices of smoking. Varenicline significantly reduced craving (Hedge's g = -0.36[-0.54,-0.17], p < 0.001), withdrawal (g = -0.25[-0.41,-0.09], p = 0.003) and behavioural indices of smoking (g = -0.36[-0.63,-0.08], p = 0.01) relative to placebo. In contrast, results were inconclusive regarding bupropion's effects on craving (g = -0.13[-0.32,0.05], p = 0.15), withdrawal (g = -0.15[-0.44,0.14], p = 0.31) and behavioural indices of smoking (g = -0.05[-0.35,0.24], p = 0.73) relative to placebo. Findings provide meta-analytic support that short-term varenicline treatment decreases craving, withdrawal symptoms and smoking behaviour under controlled laboratory conditions. However, findings also suggest the ability of human laboratory paradigms to detect pharmacotherapy effects may differ by treatment type. Pharmacotherapy discovery and evaluation efforts utilizing human laboratory methods should aim to align study designs and laboratory procedures with presumed therapeutic mechanisms when possible.
人类实验室研究被广泛用于评估药物治疗效果的行为机制。目前尚未对评估戒烟药物治疗的人类实验室研究结果进行综合分析。本项荟萃分析旨在综合分析随机、安慰剂对照的人类实验室研究中,非尼古丁类药物治疗对与戒烟相关的结果的影响。文献检索确定了 15 项关于伐伦克林(n=697)和 9 项关于安非他酮(n=313)的人类实验室研究,这些研究有足够的数据可以纳入分析。这些研究涉及急性或亚急性药物治疗,药物使用时间从单次剂量到 8 周不等。主要结果是评估渴望、戒断和吸烟行为指标。与安慰剂相比,伐伦克林显著降低了渴望(Hedge's g=-0.36[-0.54,-0.17],p<0.001)、戒断(g=-0.25[-0.41,-0.09],p=0.003)和吸烟行为指标(g=-0.36[-0.63,-0.08],p=0.01)。相比之下,关于安非他酮对渴望(g=-0.13[-0.32,0.05],p=0.15)、戒断(g=-0.15[-0.44,0.14],p=0.31)和吸烟行为指标(g=-0.05[-0.35,0.24],p=0.73)的影响,结果尚无定论。这些发现为短期使用伐伦克林治疗可降低控制实验室条件下的渴望、戒断症状和吸烟行为提供了荟萃分析支持。然而,这些发现也表明,人类实验室范式检测药物治疗效果的能力可能因治疗类型而异。在可能的情况下,利用人类实验室方法进行药物治疗发现和评估的努力应旨在使研究设计和实验室程序与预期的治疗机制保持一致。