Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

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 recent (past two years) MDD. Five hundred and
seventy-six 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.

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.

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