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.

Public Health Relevance

This is the first adequately powered study of the efficacy and safety of bupropion, an approved treatment for smoking cessation, in pregnant smokers. The placebo-controlled study will also examine whether changes in craving and depressive symptoms are responsible for the observed effects on smoking cessation and will explore whether genetic, metabolic, and social/behavioral factors can identify which pregnant smokers are the best candidates for bupropion treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA184315-01
Application #
8674159
Study Section
Special Emphasis Panel (ZRG1-RPIA-N (09))
Program Officer
Morgan, Glen D
Project Start
2014-08-15
Project End
2019-07-31
Budget Start
2014-08-15
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$693,298
Indirect Cost
$165,083
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104