Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

• ClinicalTrials.gov Identifier: NCT02378714
• Recruitment Status: Completed
• First Posted: March 4, 2015
• Results First Posted: May 27, 2021
• Last Update Posted: July 29, 2021
• Sponsor: Northwestern University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Brian Hitsman, Northwestern University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence; Major Depressive Disorder	Drug: Varenicline; Behavioral: BASC; Behavioral: Standard treatment	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers
• Actual Study Start Date: July 24, 2015
• Actual Primary Completion Date: March 13, 2020
• Actual Study Completion Date: March 13, 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Standard treatment + placebo varenicline; Standard behavioral smoking cessation treatment plus placebo varenicline	Behavioral: Standard treatment; 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.; Other Name: Standard Therapy
Experimental: BASC + placebo varenicline; Behavioral activation for smoking cessation plus placebo varenicline	Behavioral: BASC; 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.; Other Name: Behavioral activation for smoking cessation
Active Comparator: Standard treatment + active varenicline; Standard behavioral smoking cessation treatment plus active varenicline	Drug: Varenicline; 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.; Other Name: Chantix; Behavioral: Standard treatment; 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.; Other Name: Standard Therapy
Experimental: BASC + active varenicline; Behavioral activation for smoking cessation plus active varenicline	Drug: Varenicline; 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.; Other Name: Chantix; Behavioral: BASC; 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.; Other Name: Behavioral activation for smoking cessation

Outcome Measures

Primary Outcome Measures :

1. Bioverified Point-prevalence Abstinence at 27 Weeks [ Time Frame: 27 weeks (24-weeks post-target quit date) ]
   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.
2. Adverse Event and Serious Adverse Event Rates [ Time Frame: Weeks 1 (1-week before starting medication), 6, and 14 (end of medication) ]

   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.

Secondary Outcome Measures :

1. Bioverified Point-prevalence Abstinence at 14 Weeks (End of Treatment) [ Time Frame: 14 weeks (11-weeks post-target quit date) ]
   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.
2. Prolonged Abstinence [ Time Frame: 27 weeks (24 weeks post target quit date) ]
   <7 consecutive days of self-reported smoking after a 2-week grace period
3. Continuous Abstinence [ Time Frame: 27 weeks (24 weeks post target quit date) ]
   No smoking between target quit date (week 3) and week 27
4. Time to 7-day Relapse [ Time Frame: 27 weeks (24 weeks post target quit date) ]
   Time to relapse as defined by 7 or more consecutive days of self-reported smoking (no grace period)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Northwestern University

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brian Hitsman, Ph.D.; Northwestern University

  Study Documents (Full-Text)

Documents provided by Brian Hitsman, Northwestern University:

Study Protocol and Statistical Analysis Plan  [PDF] June 25, 2019

Informed Consent Form  [PDF] August 21, 2019

More Information

Additional Information:

FDA Product Information for Varenicline 

Publications:

Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, Yunis C. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med. 2013 Sep 17;159(6):390-400. doi: 10.7326/0003-4819-159-6-201309170-00005. Erratum In: Ann Intern Med. 2013 Oct 15;159(8):576.

Blalock JA, Robinson JD, Wetter DW, Schreindorfer LS, Cinciripini PM. Nicotine withdrawal in smokers with current depressive disorders undergoing intensive smoking cessation treatment. Psychol Addict Behav. 2008 Mar;22(1):122-8. doi: 10.1037/0893-164X.22.1.122.

Ebbert JO, Wyatt KD, Hays JT, Klee EW, Hurt RD. Varenicline for smoking cessation: efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010 Oct 5;4:355-62. doi: 10.2147/ppa.s10620.

Gierisch JM, Bastian LA, Calhoun PS, McDuffie JR, Williams JW Jr. Smoking cessation interventions for patients with depression: a systematic review and meta-analysis. J Gen Intern Med. 2012 Mar;27(3):351-60. doi: 10.1007/s11606-011-1915-2. Epub 2011 Oct 26.

Hitsman B, Moss TG, Montoya ID, George TP. Treatment of tobacco dependence in mental health and addictive disorders. Can J Psychiatry. 2009 Jun;54(6):368-78. doi: 10.1177/070674370905400604.

Hitsman B, Papandonatos GD, McChargue DE, DeMott A, Herrera MJ, Spring B, Borrelli B, Niaura R. Past major depression and smoking cessation outcome: a systematic review and meta-analysis update. Addiction. 2013 Feb;108(2):294-306. doi: 10.1111/add.12009.

Philip NS, Carpenter LL, Tyrka AR, Whiteley LB, Price LH. Varenicline augmentation in depressed smokers: an 8-week, open-label study. J Clin Psychiatry. 2009 Jul;70(7):1026-31. doi: 10.4088/jcp.08m04441. Epub 2009 Mar 24.

MacPherson L, Tull MT, Matusiewicz AK, Rodman S, Strong DR, Kahler CW, Hopko DR, Zvolensky MJ, Brown RA, Lejuez CW. Randomized controlled trial of behavioral activation smoking cessation treatment for smokers with elevated depressive symptoms. J Consult Clin Psychol. 2010 Feb;78(1):55-61. doi: 10.1037/a0017939.

• Responsible Party: Brian Hitsman, Associate Professor of Preventive Medicine, Northwestern University
• ClinicalTrials.gov Identifier: NCT02378714
• Other Study ID Numbers: STU00100303; 1R01CA184211-01A1 ( U.S. NIH Grant/Contract )
• First Posted: March 4, 2015
• Results First Posted: May 27, 2021
• Last Update Posted: July 29, 2021
• Last Verified: May 2021

Keywords provided by Brian Hitsman, Northwestern University:

Smoking Cessation; Major Depressive Disorder; Nicotine Dependence; Varenicline; Behavioral Activation Therapy; Cigarette Smoking

Additional relevant MeSH terms:

Tobacco Use Disorder; Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs