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

Abstract

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. Trial Registration: clinicaltrials.gov Identifier: NCT00507728.

Depression and Smoking Cessation: Evidence from a Smoking Cessation Clinic with 1-Year Follow-Up

“…The reduction in abstinence predicted by depressive symptoms is in line with previous research [12][13][14]17]. There was no evidence of differential effects by gender as found in previous studies [16,17].…”

“…This was not treated as pharmacotherapy in analysis and not taken into account for categorisation findings of a meta-analysis [9]. Although reduction differed by medication, we found no evidence of a particularly strong effect of varenicline as previously described [12]. The present findings extend the evidence on the association between depression and subsequent smoking abstinence by focusing on the current level of depression diagnosed using a validated and well-established measure and by including mild depression as well as more severe depression [16].…”

“…However, in a longitudinal study in older smokers, quitting smoking had no impact on depression [11]. Others have found changes in depression to vary depending on the stop smoking medication used [12].…”

Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…After the removal of duplicates and screening of titles and abstracts, 68 trials underwent full‐text review. In total, 38 RCTs met all eligibility criteria and were included in our meta‐analysis 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49…”

Activation ofα4β2*/α6β2* Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

“…Varenicline (Chantix; Pfizer, Groton, CT), a partial agonist at a4b2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at a7 and a3b4 nAChRs is currently the best in class treatment of smoking cessation (Coe et al, 2005;Garrison and Dugan, 2009). However, although varenicline has been shown to improve both concentration and depressed mood and mitigate craving, recent studies in mice and human subjects have shown treatment does not improve nicotine withdrawal-induced anxiety (Turner et al, 2013b;Cinciripini et al, 2013). This may be of special importance because anxiety arising due to nicotine withdrawal has been correlated with relapse rates (Zhou et al, 2009).…”