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Grant Details

Grant Number: 5R01CA184211-05 Interpret this number
Primary Investigator: Hitsman, Brian
Organization: Northwestern University At Chicago
Project Title: Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers
Fiscal Year: 2018


DESCRIPTION (provided by applicant): This project answers many prominent but largely unanswered calls over the last decade to address tobacco dependence in persons with mental health disorders, especially major depressive disorder (MDD). Upwards of 43% of persons with MDD are daily smokers who are more likely to smoke heavily, show greater tobacco dependence, suffer more severe withdrawal, and experience lower quit rates than smokers without MDD. Very little is known about treatment strategies that might optimize smoking cessation for smokers with MDD because almost all randomized clinical trials have excluded these smokers. We conducted a meta-analysis of 42 randomized clinical trials (RCTs) comprising nearly 3000 smokers with past MDD given that these data were routinely collected and offer insight into potential treatment approaches for patients with current or recent MDD. Results showed that CBT mood management (CBT MM) and varenicline individually had the strongest associations with short-term abstinence. Varenicline also had the strongest association with long-term abstinence. Behavioral activation (BA) is simpler to administer and easier for patients to understand than CBT MM and therefore may enhance skill acquisition/retainment and long-term abstinence. The goal of BA is to increase engagement in rewarding activities, a problem for smokers with MDD who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of avoidance, withdrawal, and inactivity. Combination treatment with BA and varenicline has great potential to improve long- term abstinence rates for smokers with current or recent MDD because it addresses the unique psychological factors that may maintain their tobacco dependence. This proposed double-blind, placebo-controlled, randomized trial will evaluate the efficacy of BA plus varenicline for treating tobacco dependence in smokers with current or recent (past year) MDD. Six hundred and thirty daily (e5 cigarettes/day) smokers with at least moderate depressive symptoms will be randomized to receive 12 weeks of one of four treatments: 1) Standard behavioral cessation treatment (ST) + placebo; 2) BA integrated with ST (BA) + placebo; 3) ST + varenicline; or 4) BA + varenicline. Both BA and ST will be administered in eight 1-hour sessions, occurring weekly for the first four weeks and biweekly for the final eight weeks. Randomization will be stratified on clinical site (Northwestern, PENN), gender, and severity of depressive symptoms (moderate vs. severe). The primary outcomes will be carbon monoxide (CO) verified 7-day point prevalence abstinence at 24-weeks post-quit. Additional aims include assessing adverse event rates between varenicline and placebo arms, and testing for mediation of treatment effects by anhedonia, cognitive function (attention and memory), cigarette reward value, and craving and withdrawal. This will be the first adequately powered trial of BA for smoking cessation in this population; the first RCT to evaluate varenicline among a community sample of smokers with MDD; and the first RCT to assess the main and combined effects of these two treatments.


Efficacy and safety of combination behavioral activation for smoking cessation and varenicline for treating tobacco dependence among individuals with current or past major depressive disorder: A 2 × 2 factorial, randomized, placebo-controlled trial.
Authors: Hitsman B. , Papandonatos G.D. , Gollan J.K. , Huffman M.D. , Niaura R. , Mohr D.C. , Veluz-Wilkins A.K. , Lubitz S.F. , Hole A. , Leone F.T. , et al. .
Source: Addiction (Abingdon, England), 2023 Sep; 118(9), p. 1710-1725.
EPub date: 2023-05-03.
PMID: 37069490
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Treatment adherence in a smoking cessation clinical trial for individuals with current or past major depressive disorder: Predictors and association with cessation.
Authors: Schnoll R. , Barrila G.M. , Dalsimer S. , Hosie Quinn M. , Bauer A.M. , Fox E. , Olonoff M. , Jao N.C. , Leone F. , Huffman M.D. , et al. .
Source: Addictive behaviors, 2023 Aug; 143, p. 107686.
EPub date: 2023-03-05.
PMID: 36893514
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Change in cardiovascular health among adults with current or past major depressive disorder enrolled in intensive smoking cessation treatment.
Authors: Carroll A.J. , Huffman M.D. , Wileyto E.P. , Khan S.S. , Fox E. , Smith J.D. , Bauer A.M. , Leone F.T. , Schnoll R.A. , Hitsman B. .
Source: Journal of affective disorders, 2023-07-15; 333, p. 527-534.
EPub date: 2023-04-28.
PMID: 37119868
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History and Correlates of Smoking Cessation Behaviors Among Individuals With Current or Past Major Depressive Disorder Enrolled in a Smoking Cessation Trial.
Authors: Quinn M.H. , Olonoff M. , Bauer A.M. , Fox E. , Jao N. , Lubitz S.F. , Leone F. , Gollan J.K. , Schnoll R. , Hitsman B. .
Source: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2022-01-01; 24(1), p. 37-43.
PMID: 34259871
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Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.
Authors: Schnoll R. , Paul Wileyto E. , Bauer A.M. , Fox E. , Leone F. , Lerman C. , Tyndale R.F. , George T.P. , Hawk L. , Cinciripini P. , et al. .
Source: The American journal on addictions, 2021 Jul; 30(4), p. 382-388.
EPub date: 2021-03-26.
PMID: 33772971
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Extended Nicotine Patch Treatment Among Smokers With and Without Comorbid Psychopathology.
Authors: Carroll A.J. , Mathew A.R. , Leone F.T. , Wileyto E.P. , Miele A. , Schnoll R.A. , Hitsman B. .
Source: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2020-01-27; 22(1), p. 24-31.
PMID: 30215785
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Longitudinal associations between smoking and affect among cancer patients using varenicline to quit smoking.
Authors: Carroll A.J. , Kim K. , Miele A. , Olonoff M. , Leone F.T. , Schnoll R.A. , Hitsman B. .
Source: Addictive behaviors, 2019 Aug; 95, p. 206-210.
EPub date: 2019-04-03.
PMID: 30978583
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Randomized evaluation of trial acceptability by INcentive (RETAIN): Study protocol for two embedded randomized controlled trials.
Authors: Krutsinger D.C. , McMahon J. , Stephens-Shields A.J. , Bayes B. , Brooks S. , Hitsman B.L. , Lubitz S.F. , Reyes C. , Schnoll R.A. , Ryan Greysen S. , et al. .
Source: Contemporary clinical trials, 2019 Jan; 76, p. 1-8.
EPub date: 2018-11-08.
PMID: 30414865
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Cancer-related disease factors and smoking cessation treatment: Analysis of an ongoing clinical trial.
Authors: Carroll A.J. , Veluz-Wilkins A.K. , Blazekovic S. , Kalhan R. , Leone F.T. , Wileyto E.P. , Schnoll R.A. , Hitsman B. .
Source: Psycho-oncology, 2018 Feb; 27(2), p. 471-476.
EPub date: 2017-08-04.
PMID: 28636795
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Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model.
Authors: Mathew A.R. , Hogarth L. , Leventhal A.M. , Cook J.W. , Hitsman B. .
Source: Addiction (Abingdon, England), 2017 Mar; 112(3), p. 401-412.
EPub date: 2016-10-26.
PMID: 27628300
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Treating Nicotine Dependence and Preventing Smoking Relapse in Cancer Patients.
Authors: Chang E.H.E. , Braith A. , Hitsman B. , Schnoll R.A. .
Source: Expert review of quality of life in cancer care, 2017; 2(1), p. 23-39.
EPub date: 2016-12-28.
PMID: 28808692
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Is the Effect of Anhedonia on Smoking Cessation Greater for Women Versus Men?
Authors: Powers J.M. , Carroll A.J. , Veluz-Wilkins A.K. , Blazekovic S. , Gariti P. , Leone F.T. , Schnoll R.A. , Hitsman B. .
Source: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2017 Jan; 19(1), p. 119-123.
EPub date: 2016-06-09.
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