Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

Northwestern University

Status and phase: Completed; Phase 4

Conditions: Major Depressive Disorder; Nicotine Dependence

Treatments: Drug: Varenicline; Behavioral: Standard treatment; Behavioral: BASC

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02378714

STU00100303

1R01CA184211-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. adult (18 years of age or older) daily cigarette smokers (1+ cigarettes per day)
2. meet criteria for current or lifetime MDD without psychotic features
3. 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
4. speak, read, and write fluently in English
5. able to provide written informed consent
6. intend to reside in the geographic area for >8 months
7. 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.
8. The candidate had to answer "yes" to the question: "Are you interested in quitting smoking?"

Exclusion criteria

1. current enrollment or plan to enroll in another smoking cessation program in the next 8 months
2. regular (daily) use of e-cigarettes, chewing tobacco, snuff, snus, or other tobacco products
3. current use or plan to use nicotine replacement therapy or other smoking cessation medication within the next 8 months
4. medications indicated for bipolar or psychotic disorder if prescribed for bipolar or psychotic disorder
5. pregnant or planning to become pregnant within the next 8 months, or breast feeding
6. history of seizures or current seizure disorder without medication
7. 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
8. any prior solid organ transplant or prior hematopoietic stem cell transplant
9. alcohol consumption exceeding 28 drinks per week
10. cirrhosis or end-stage liver disease
11. systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg after two readings or symptomatic uncontrolled stage II hypertension
12. unstable cardiovascular disease within 3 months prior to baseline or other cardiovascular disease requiring hospitalization
13. prior hospitalization for heart failure
14. previous allergic reaction to varenicline
15. high suicide risk based on the Columbia Suicide Severity Rating Scale
16. lifetime bipolar or psychotic disorder as determined by either self-report or clinical interview

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 4 patient groups, including a placebo group

Standard treatment + placebo varenicline

Placebo Comparator group

Description:

Standard behavioral smoking cessation treatment plus placebo varenicline

Treatment:

Behavioral: Standard treatment

BASC + placebo varenicline

Experimental group

Description:

Behavioral activation for smoking cessation plus placebo varenicline

Treatment:

Behavioral: BASC

Standard treatment + active varenicline

Active Comparator group

Description:

Standard behavioral smoking cessation treatment plus active varenicline

Treatment:

Behavioral: Standard treatment

Drug: Varenicline

BASC + active varenicline

Experimental group

Description:

Behavioral activation for smoking cessation plus active varenicline

Treatment:

Behavioral: BASC

Drug: Varenicline