Effects of sequential fluoxetine and gender on prequit depressive symptoms, affect, craving, and quit day abstinence in smokers with elevated depressive symptoms: a growth curve modeling approach

Abstract

Although the important roles of postquit affect and withdrawal symptoms in the process of smoking cessation have been well established, little is known about the relations between prequit affective trajectories and cessation outcome on the target quit date (TQD). This study examined whether a 16-week course of fluoxetine initiated 8 weeks prequit ("sequential" fluoxetine) improved TQD abstinence relative to placebo through its effects on prequit depressive symptoms, affect (withdrawal-relevant negative affect, general negative affect, and positive affect), and craving to smoke among 206 smokers with elevated depressed symptoms. The moderating effects of gender were also examined. In total, 83 smokers (40%) failed to achieve abstinence on TQD, with no difference between treatment conditions or gender. Overall structural equation models showed that fluoxetine had significant indirect effects on TQD abstinence through changes in prequit withdrawal-relevant negative affect and craving, but not depressive symptoms. However, multigroup analyses revealed gender differences. Sequential fluoxetine reduced prequit depressive symptoms, withdrawal-relevant negative affect, and craving only among women. Reduction in prequit depressive symptoms and craving among women, and withdrawal-relevant negative affect among men was associated with TQD abstinence. Moreover, exploratory analysis showed negative trend-level indirect effects of fluoxetine on TQD abstinence via increased side effects, regardless of gender. This study demonstrated the importance of considering gender when examining treatment efficacy. Identifying ways to further reduce prequit depressive symptoms and craving for women and withdrawal-relevant negative affect for men whereas alleviating side effects may help smokers with elevated depressed symptoms achieve the first smoking cessation milestone.

Figure 1

CONSORT diagram for enrollment and allocation of participants for sequential fluoxetine and placebo conditions.

Figure 2

General path diagram for indirect models. The direct relationships between treatment to smoking outcome (1 = abstinent, 0 = smoking) on target quit date (TQD) are depicted in path c’. Path a_s represents treatment condition (1 = sequential fluoxetine, 0 = sequential placebo) predicting latent ‘pre-quit slope’ (changes over 8 weeks prior to quit date) variables, while paths b_i and b_s indicate the relationships between ‘pre-treatment intercept’ and ‘pre-quit slope’ and abstinence on TQD. Gender and nicotine dependence (FTND) were included as baseline covariates, predicting ‘pre-treatment intercept,’ ‘pre-quit slope,’ and abstinence on TQD (shown in dotted lines).

Figure 3

Pre-quit changes by treatment condition and gender. Plots show changes (in raw scores) in withdrawal-relevant negative affect (scores range from 1 to 4) (A), craving (scores range from 1 to 4) (B), and depressive symptoms (scores range from 0 to 60) (C) over 8 weeks prior to target quit date (TQD) by treatment condition (Sequential Fluoxetine vs. Sequential Placebo) and gender. Plots for general negative affect (scores range from 10 to 50) (D) and general positive affect (scores range from 10 to 50) (E) show overall changes by treatment condition given that no significant differences in changes in general negative or positive affect were observed across gender.