Effects of Varenicline and Bupropion Sustained-Release Use Plus Intensive Smoking Cessation Counseling on Prolonged Abstinence From Smoking and on Depression, Negative Affect, and Other Symptoms of Nicotine Withdrawal

JAMA Psychiatry (Impact Factor: 12.01). 03/2013; 70(5):1-12. DOI: 10.1001/jamapsychiatry.2013.678
Source: PubMed


Importance: Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness. Objective: To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning. Design and Setting: Placebo-controlled randomized clinical trial at a university medical center. Participants: In total, 294 community volunteers who wanted to quit smoking. Interventions: Twelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling). Main Outcome Measures: Prolonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal. Results: Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events. Conclusions and Relevance: In a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events.

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    • "One key strategy to reduce urge and relapse risk would be to reduce negative affect and downstream effects on expectancies and urge. For example, pharmacotherapies such as bupropion and varenicline have been demonstrated to decrease levels of negative affect during a quit attempt (Cinciripini et al., 2013; West, Baker, Cappelleri & Bushmakin, 2008). Furthermore, some research suggests that varenicline and nicotine vaccines may reduce the rewarding effects of smoking during a quit attempt; thus, potentially reducing positive smoking outcome expectancies (Hartmann-Boyce, Stead, Cahill, & Lancaster, in press; West et al., 2008). "
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    ABSTRACT: Ecological momentary assessment was used to examine associations between negative affect, positive smoking outcome expectancies, and smoking urge during the first 7 days of a smoking quit attempt. Participants were 302 female smokers who enrolled in an individually tailored smoking cessation treatment study. Multilevel mediation analysis was used to examine the temporal relationship among the following: (a) the effects of negative affect and positive smoking outcome expectancies at 1 assessment point (e.g., time j) on smoking urge at the subsequent time point (e.g., time j + 1) in Model 1; and, (b) the effects of negative affect and smoking urge at time j on positive smoking outcome expectancies at time j + 1 in Model 2. The results from Model 1 showed a statistically significant effect of negative affect at time j on smoking urge at time j + 1, and this effect was mediated by positive smoking outcome expectancies at time j, both within- and between-participants. In Model 2, the within-participant indirect effect of negative affect at time j on positive smoking outcome expectancies at time j + 1 through smoking urge at time j was nonsignificant. However, a statistically significant indirect between-participants effect was found in Model 2. The findings support the hypothesis that urge and positive smoking outcome expectancies increase as a function of negative affect, and suggest a stronger effect of expectancies on urge as opposed to the effect of urge on expectancies. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Experimental and Clinical Psychopharmacology 05/2014; 22(4). DOI:10.1037/a0036749 · 2.71 Impact Factor
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    ABSTRACT: To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. In the 39 randomised controlled trials (10 761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however, : are already well recognised. PROSPERO 2014:CRD42014009224. © Thomas et al 2015.
    BMJ Clinical Research 350:h1109. · 14.09 Impact Factor
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    ABSTRACT: Background: Smoking cessation for individuals with depressive disorders represents an important clinical issue. It often has been hypothesized that smoking cessation worsens negative affect as part of the withdrawal process in this population. However, studies examining the impact of smoking cessation on changes in affect in smokers with depression are limited and equivocal. Methods: This study examines affective processes in smokers with depression undergoing a 12-week smoking cessation intervention (N = 49). We used the Positive and Negative Affect Scale to measure participants' positive affect (PA) and negative affect (NA) trajectories over the course of a quit attempt. We examined whether affective treatment response across the trial differed by prolonged smoking abstinence status and whether postquit affect differed by prequit affective treatment response, as well as the interaction of prequit affective response and abstinence status. Results: Prolonged abstainers showed significant increases in PA over the course of a quit attempt compared with nonabstainers. Prequit affective trajectories significantly predicted postquit affect for measures of both PA and NA. Lastly, the interaction of prequit affective trajectory and abstinence significantly predicted postquit levels of NA but not PA. Conclusions: This study adds to a burgeoning body of research demonstrating that significant improvements in psychological functioning can be observed among those who successfully quit smoking even in the most severe psychiatric group.
    Nicotine & Tobacco Research 03/2013; 15(11). DOI:10.1093/ntr/ntt036 · 3.30 Impact Factor
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