The frequent co-occurrence of smoking and MDD in pregnant women with SUD, coupled with the desire to limit fetal exposure to multiple toxins, provides the rationale for identifying a single drug to treat both smoking and MDD in this population. Data from this study show a trend towards a greater reduction in smoking in depressed pregnant smokers using bupropion compared to citalopram/escitalopram, with decreases for bupropion similar to that seen in patients who are not depressed. Bupropion users in this study also had a greater improvement in mood rating compared to citalopram/escitalopram users. These differences occurred despite similarly prescribed effective doses of each antidepressant.
One interpretation of these findings is that bupropion is just as effective as no medication treatment for smoking, and that citalopram/escitalopram is worse than no treatment as a smoking cessation aid (i.e., that citalopram/escitalopram might actually worsen the likelihood that a patient would stop smoking). However, the no antidepressant group differed in two important ways from the antidepressant groups – first, in the use of an antidepressant medication, and second, in the presence of a depressive disorder. Ideally, the bupropion and citalopram/escitalopram groups would be compared to a group of depressed smokers who received no medication treatment (or placebo). However, in the absence of such a group, the findings for the citalopram/escitalopram patients should not be over interpreted as suggesting citalopram/escitalopram worsens outcome.
The fact that bupropion showed a trend toward some efficacy is promising, especially given that bupropion was not used specifically as a smoking cessation aid in these patients. Thus, target quit dates designed relative to the start of medication were not set, and other behavioral and counseling interventions for smoking cessation were not specified with these patients. Such interventions would be expected to produce better outcomes for patients treated with bupropion.
This study has several limitations. It used broadly defined measures of smoking and mood. A prospective trial examining smoking and mood could include more comprehensive and sensitive measures and yield results supporting stronger conclusions. The short duration of time on bupropion or citalopram/escitalopram required for study inclusion, non-observed medication use, and differences in duration of time on drug between the two groups may minimize smoking and mood findings. Although the mean bupropion dose prescribed is adequate in non-pregnant substance-dependent populations for smoking cessation response, it has not been studied in pregnant patients and may minimize smoking findings in the present study. The lack of observed medication ingestion may also minimize smoking and mood findings. In addition, heterogeneity of women’s trimester status, co-occurring psychiatric disorders (which were not systematically assesed), ongoing substance abuse, and control medications may have played a role in the outcomes. Sample sizes are modest and may limit the power to detect differences. Also noteworthy is the recent FDA-required new Boxed Warnings
, highlighting the risk of serious neuropsychiatric symptoms in patients using smoking cessation aids varenicline and bupropion. These symptoms include changes in behavior, agitation, depressed mood, suicidal thoughts, and attempted suicide.34
(The same changes will also be required for bupropion’s indication for the treatment of depression and seasonal affective disorder.) Despite these limitations, the present study provides some of the first data examining the relationship between bupropion and smoking in pregnant women enrolled in comprehensive drug treatment.
These results comparing bupropion and citalopram/escitalopram demonstrate a trend towards a greater reduction in cigarettes smoked and greater improvement in mood for women treated with bupropion. This suggests the value in further studying the smoking cessation efficacy and safety of bupropion in populations of pregnant substance-dependent smokers.