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佳的最重要的可改变原因之一，并且使分娩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患有抑郁症的妇女中，这一比例更高。对怀孕期间吸烟的行为治疗是适度有效的，在一般人群中，用于戒烟的一线药物的安全性和有效性通常没有被评估在怀孕期间使用。安非他酮可能有效治疗孕妇的尼古丁依赖，因为：1)妊娠增加了尼古丁代谢，降低了尼古丁替代疗法的疗效~相反，安非他酮对尼古丁快速代谢者的尼古丁依赖有效~ 2)安非他酮目前被广泛用于治疗孕妇抑郁症，这是该人群继续吸烟的一个重要危险因素~ 3)妊娠增加了CYP2B6酶的活性，可能增加了安非他酮的代谢和羟安非他酮的浓度。这与更好的戒烟效果有关。重要的是，数据表明，安非他酮在怀孕前三个月后可以安全使用。该研究的具体目的是：1)对来自低收入、服务不足社区的360名怀孕吸烟者（13-24周）进行为期10周的安慰剂对照试验，服用300毫克/天的安非他酮。我们将在治疗期间监测吸烟行为和药物的不良影响，并在剩余的妊娠期间进行随访（测量妊娠长度、妊娠并发症发生率和分娩结果），并在产后三个月进行随访。我们将使用短信发送怀孕相关信息，以提高服药依从性。2)评估抑郁症状和渴望的变化作为安非他酮对戒烟率影响的中介。目的：探讨安非他酮对香烟戒断和安全性的遗传、代谢和社会/行为调节因子。这将是第一个充分证实安非他酮治疗尼古丁依赖孕妇的有效性和安全性的临床试验。该试验的创新之处是使用短信来提高孕妇的治疗依从性，并对安非他酮治疗的调节剂和调节剂进行前瞻性评估。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.