Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

Study Overview
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Brief Summary
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Persons who struggle with depression smoke at high rates and experience low quit rates in treatment. The best way to improve cessation treatment for this underserved population remains unknown. The proposed trial tests whether the combination of varenicline and behavioral mood management treatment enhances long-term abstinence for depressed smokers and, if so, whether this treatment achieves its effects through addressing the unique psychological factors that appear to maintain tobacco dependence for these smokers.

Detailed Description
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Upwards of 43% of persons with major depressive disorder (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. 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. 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). Using a double-blind, placebo-controlled, randomized design, the investigators will evaluate the efficacy of behavioral activation for smoking cessation (BASC) plus varenicline for treating tobacco dependence in smokers with current or lifetime MDD. Three hundred and thirty daily (≥1 cigarettes/day) smokers will be randomized to receive 12 weeks of one of four treatments: 1) Standard behavioral cessation treatment (ST) + placebo; 2) Behavioral activation integrated with ST (BASC) + placebo; 3) ST + varenicline; or 4) BASC + varenicline. Both BASC and ST will be administered in eight 45 minute sessions, occurring weekly for the first four weeks and biweekly for the final eight weeks. Randomization will be stratified on clinical site (Northwestern, University of Pennsylvania), gender, and severity of depressive symptoms (minimal/mild vs. moderate/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 randomized controlled trial will be the first adequately powered trial of BASC in this population; the first trial to evaluate varenicline among a community sample of smokers with MDD; and the first trial to assess the main and combined effects of these two treatments.

Official Title
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Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

Conditions
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Nicotine Dependence, Major Depressive Disorder

Intervention / Treatment
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* Drug: Varenicline
* Behavioral: BASC
* Behavioral: Standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: adult (18 years of age or older) daily cigarette smokers (1+ cigarettes per day) meet criteria for current or lifetime MDD without psychotic features have or are willing to acquire a personal email address and access to a camera phone or other method for submission of therapy practice assignments speak, read, and write fluently in English able to provide written informed consent intend to reside in the geographic area for >8 months women of childbearing potential must agree to use a medically acceptable method of birth control or abstain from sexual intercourse during the time they are taking study medication and for at least one month after the medication period ends. The candidate had to answer yes to the question: Are you interested in quitting smoking? Exclusion criteria: current enrollment or plan to enroll in another smoking cessation program in the next 8 months regular (daily) use of e-cigarettes, chewing tobacco, snuff, snus, or other tobacco products current use or plan to use nicotine replacement therapy or other smoking cessation medication within the next 8 months medications indicated for bipolar or psychotic disorder if prescribed for bipolar or psychotic disorder pregnant or planning to become pregnant within the next 8 months, or breast feeding history of seizures or current seizure disorder without medication history of severe (stage IV or V) chronic kidney disease including current or prior end stage renal disease on either hemodialysis or peritoneal dialysis or prior renal transplant any prior solid organ transplant or prior hematopoietic stem cell transplant alcohol consumption exceeding 28 drinks per week cirrhosis or end-stage liver disease systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg after two readings or symptomatic uncontrolled stage II hypertension unstable cardiovascular disease within 3 months prior to baseline or other cardiovascular disease requiring hospitalization prior hospitalization for heart failure previous allergic reaction to varenicline high suicide risk based on the Columbia Suicide Severity Rating Scale lifetime bipolar or psychotic disorder as determined by either self-report or clinical interview

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard treatment + placebo varenicline<br>Standard behavioral smoking cessation treatment plus placebo varenicline | Behavioral: Standard treatment<br>* Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.<br>* Other names: Standard Therapy;|
| Experimental: BASC + placebo varenicline<br>Behavioral activation for smoking cessation plus placebo varenicline | Behavioral: BASC<br>* The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.<br>* Other names: Behavioral activation for smoking cessation;|
| Active Comparator: Standard treatment + active varenicline<br>Standard behavioral smoking cessation treatment plus active varenicline | Drug: Varenicline<br>* Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.<br>* Other names: Chantix;Behavioral: Standard treatment<br>* Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.<br>* Other names: Standard Therapy;|
| Experimental: BASC + active varenicline<br>Behavioral activation for smoking cessation plus active varenicline | Drug: Varenicline<br>* Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.<br>* Other names: Chantix;Behavioral: BASC<br>* The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.<br>* Other names: Behavioral activation for smoking cessation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioverified Point-prevalence Abstinence at 27 Weeks | Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 27 (24 weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 27. | 27 weeks (24-weeks post-target quit date) | 
| Adverse Event and Serious Adverse Event Rates | Adverse event and serious adverse event rates between varenicline and placebo arms. A previously developed algorithm was used to classify side effect reports as adverse events (AEs) or serious adverse events (SAEs) (Schnoll et al. 2019). Reference: Schnoll, R., Leone, F., Weisbrot, J., Veluz-Wilkins, A., Miele, A., Hole, A., Jao, N.C., Wileyto, E.P., Carroll, A.J., Kalhan, R., Patel, J., Langer, C., & Hitsman, B. (2019). A randomized controlled trial of 24-weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Psycho-Oncology, 28, 561-569. | Weeks 1 (1-week before starting medication), 6, and 14 (end of medication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioverified Point-prevalence Abstinence at 14 Weeks (End of Treatment) | Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 14 (11-weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 14. | 14 weeks (11-weeks post-target quit date) | 
| Prolonged Abstinence | <7 consecutive days of self-reported smoking after a 2-week grace period | 27 weeks (24 weeks post target quit date) | 
| Continuous Abstinence | No smoking between target quit date (week 3) and week 27 | 27 weeks (24 weeks post target quit date) | 
| Time to 7-day Relapse | Time to relapse as defined by 7 or more consecutive days of self-reported smoking (no grace period) | 27 weeks (24 weeks post target quit date) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking Cessation, Major Depressive Disorder, Nicotine Dependence, Varenicline, Behavioral Activation Therapy, Cigarette Smoking