Placebo-controlled trial of bupropion for smoking cessation in pregnant women

描述（由申请人提供）：在美国，怀孕期间吸烟是导致妊娠结局不良的最重要的可改变原因之一，并使低出生体重新生儿的风险增加一倍。10%的孕妇继续吸烟，在社会经济地位较低的妇女和抑郁症患者中吸烟率更高。怀孕期间吸烟的行为治疗是适度有效的，一般人群中戒烟的一线药物的安全性和有效性通常没有在怀孕期间使用进行评估。安非他酮可能有效治疗孕妇的尼古丁依赖，因为：1）怀孕增加尼古丁代谢，从而降低尼古丁替代疗法的疗效~相反，安非他酮可有效治疗尼古丁快速代谢者的尼古丁依赖~ 2）安非他酮目前广泛用于治疗孕妇抑郁症，这是该人群继续吸烟的一个强风险因素~和3）怀孕增加了CYP 2B 6酶的活性，潜在地增加了安非他酮的代谢和羟基安非他酮的浓度，这与更好的戒烟结果有关。重要的是，数据表明，安非他酮可以在怀孕的前三个月后安全使用。本研究的具体目的是：1）在来自低收入、服务不足社区的360名怀孕吸烟者（妊娠13-24周）中进行为期10周的安非他酮300 mg/天安慰剂对照试验。我们将在治疗期间监测吸烟行为和药物的不良反应，并随访妊娠的剩余时间（测量妊娠时间，妊娠并发症发生率和分娩结局）以及产后3个月。我们将使用短信发送妊娠相关信息，以提高药物依从性。2)评估抑郁症状和渴求的变化作为安非他酮对戒烟率影响的介质。3）：探索遗传、代谢和社会/行为调节剂安非他酮对戒烟和安全性的有效性。这将是第一个充分把握安非他酮治疗妊娠吸烟者尼古丁依赖的有效性和安全性的临床试验。该试验是创新的，在其使用短信，以提高治疗的依从性和前瞻性评估的调解人和调解人的安非他酮治疗孕妇。重要的是，如果安非他酮对怀孕吸烟者有效，它的使用可以降低美国不良妊娠结局的发生率。

DESCRIPTION (provided by applicant): Cigarette smoking during pregnancy is one of the most important modifiable causes of poor pregnancy outcomes in the US and doubles the risk of delivering a low-birth-weight neonate. Ten percent of pregnant women continue to smoke, with higher rates among women in lower socioeconomic groups and in those with depression. Behavioral treatments for smoking during pregnancy are modestly effective and the safety and efficacy of first-line medications for smoking cessation in the general population have generally not been evaluated for use during pregnancy. Bupropion may be efficacious to treat nicotine dependence in pregnant women because: 1) pregnancy increases nicotine metabolism, which reduces the efficacy of nicotine replacement therapy~ in contrast, bupropion is efficacious in treating nicotine dependence in fast metabolizers of nicotine~ 2) bupropion is currently used widely to treat depression in pregnant women which is a strong risk factor for continued smoking in this group~ and 3) pregnancy increases the activity of the CYP2B6 enzyme, potentially increasing bupropion metabolism and the concentration of hydroxybupropion, which has been associated with better smoking-cessation outcomes. Importantly, data indicate that bupropion can be used safely after the first trimester of pregnancy. The specific aims of the study are: 1) To conduct a 10-week, placebo-controlled trial of bupropion 300 mg/day in 360 pregnant smokers (13-24 weeks gestation) from low- income, under-served communities. We will monitor smoking behavior and adverse effects of the medication during treatment, with follow up for the remainder of the pregnancy (measuring length of gestation, rate of pregnancy complications, and birth outcomes), and at three months postpartum. We will use text messages to send pregnancy-relevant information to enhance medication adherence. 2) To assess changes in depression symptoms and craving as mediators of bupropion's effect on quit rates. 3): To explore genetic, metabolic, and social/behavioral moderators of the efficacy of bupropion on cigarette abstinence and safety. This will be the first adequately powered clinical trial of the efficacy and safety of bupropion for nicotine dependence in pregnant smokers. The trial is innovative in its use of text messaging to enhance treatment adherence and the prospective evaluation of mediators and moderators of bupropion therapy in pregnant women. Importantly, if bupropion is efficacious in pregnant smokers, its use could reduce the rate of poor pregnancy outcomes in the United States.