Evidence-based Synthesis Program 

(ESP)

Comparative Effectiveness of Smoking Cessation 

Treatments for Patients With Depression: A 

Systematic Review and Meta-analysis of the 

Evidence

Jennifer M. Gierisch, PhD, MPH

Lori A. Bastian, MD, MPH

Center for Health Services Research in Primary Care

Durham VAMC

February 28, 2011
Evidence-based Synthesis Program 

(ESP)

Disclosure

This report is based on research conducted by the Evidence-based Synthesis 

Program (ESP) Center located at the Durham VA Medical Center, Durham, NC,

funded by the Department of Veterans Affairs, Veterans Health Administration, 

Office of Research and Development, Health Services Research and Development. 

The findings and conclusions in this document are those of the author(s) who are 

responsible for its contents; the findings and conclusions do not necessarily 

represent the views of the Department of Veterans Affairs or the United States 

government. Therefore, no statement in this article should be construed as an 

official position of the Department of Veterans Affairs. No investigators have any 

affiliations or financial involvement (e.g., employment, consultancies, honoraria, 

stock ownership or options, expert testimony, grants or patents received or 

pending, or royalties) that conflict with material presented in the report.
Evidence-based Synthesis Program 

(ESP)

VA Evidence-based Synthesis (ESP)

Program Overview

• Sponsored by VA Office of R&D and HSR&D.

• Established to provide timely and accurate syntheses/reviews of healthcare 

topics identified by VA clinicians, managers and policy-makers, as they 

work to improve the health and healthcare of Veterans. 

• Builds on staff and expertise already in place at the Evidence-based 

Practice Centers (EPC) designated by AHRQ. Four of these EPCs are also 

ESP Centers: 

o Durham VA Medical Center; VA Greater Los Angeles Health Care 

System; Portland VA Medical Center; and Minneapolis VA Medical 

Center.
Evidence-based Synthesis Program 

(ESP)

• Provides evidence syntheses on important clinical practice topics relevant 

to Veterans, and these reports help:

o develop clinical policies informed by evidence, 

o the implementation of effective services to improve patient 

outcomes and to support VA clinical practice guidelines and 

performance measures, and 

o guide the direction for future research to address gaps in clinical 

knowledge.

• Broad topic nomination process – e.g. VACO, VISNs, field – facilitated by 

ESP Coordinating Center (Portland) through online process: 

http://www.hsrd.research.va.gov/publications/esp/TopicNomination.cfm
Evidence-based Synthesis Program 

(ESP)

• Steering Committee representing research and operations (PCS, OQP, ONS, 

and VISN) provides oversight and guides program direction.

• Technical Advisory Panel (TAP)

o Recruited for each topic to provide content expertise.

o Guides topic development; refines the key questions.

o Reviews data/draft report.

• External Peer Reviewers & Policy Partners

o Reviews and comments on draft report

• Final reports posted on VA HSR&D website and disseminated widely 

through the VA. 

http://www.hsrd.research.va.gov/publications/esp/reports.cfm
Evidence-based Synthesis Program 

(ESP)

Current Report

Comparative Effectiveness of Smoking Cessation 

Treatments for Patients With Depression: 

A Systematic Review and 

Meta-analysis of the Evidence 

(Nov, 2010)

Full-length report available on ESP website:

http://www.hsrd.research.va.gov/publications/esp/reports.cfm
Evidence-based Synthesis Program 

(ESP)

Acknowledgements

Co-Authors:

Lori A. Bastian, MD, MHSc 

Patrick S. Calhoun, PhD

Jennifer R. McDuffie, PhD

John W. Williams, Jr., MD, MHSc

Medical Editor:

Liz Wing, MA

Expert Reviewers:

Kim Hamlett-Berry, PhD

Linda Humphrey, MD

Daniel Kivlahan, PhD

Andrew Saxon, MD

Scott Sherman, MD, MPH

Angela Webster, PhD
Evidence-based Synthesis Program 

(ESP)

Background

• Cigarette use is deadly but still common.

• Cigarette use is higher among Veterans with depression.

• Depression may be a barrier to smoking cessation.

• Smokers with depression can quit.
Evidence-based Synthesis Program 

(ESP)

Background

• Evidence-based smoking cessation intervention strategies: 

 Nicotine replacement therapy (NRT)

 Some antidepressants (i.e., bupropion, nortriptyline)

 Behavioral counseling (including proactive telephone counseling)

 Behavioral counseling + pharmacotherapy = gold standard care 

• Moderator effects?

• Gender

• Depression status

• Content delivery sequencing
Evidence-based Synthesis Program 

(ESP)

METHODS
Key Questions

For patients with a history of a depressive disorder or current significant depressive 

symptoms:

• KQ1: What is the comparative effectiveness of different smoking cessation 

strategies on smoking abstinence rates?

• KQ2: Are there differential effects of smoking cessation strategies by 

depression status (i.e., history of MDD, current depressive symptoms, current 

MDD)?

• KQ3: Are there differential effects of smoking cessation strategies by gender? 

• KQ4: Does treatment effectiveness differ by whether smoking 

cessation/depression treatments are delivered concurrently or sequentially?

• Key Question 5: What is the nature and frequency of adverse effects of 

smoking cessation treatments?
Study Eligibility 

Study characteristic Inclusion criteria

Study design RCTs or a secondary data analysis from RCTs

Population Adults age 18 and over with a history of a depressive disorder or 

current significant depressive symptoms

Interventions Any patient-level smoking cessation strategies alone or in combination 

with other strategies

Comparators Active comparators or control 

Setting Outpatient (e.g., mental health clinics, primary care) or delivered 

through remote communication technologies (e.g., telephone, Web)

Outcome Smoking abstinence reported at ≥ 3 months postrandomization
Data Synthesis

• Pooled risk ratios with 95% CI

• Grouped studies as. . . 

• antidepressants

• nicotine replacement therapy (NRT) 

• brief smoking cessation counseling 

• smoking cessation behavioral counseling 

• behavioral mood management therapy 

• A priori moderator analysis by. . . 

• gender

• depression status

• treatment sequencing
Evidence-based Synthesis Program 

(ESP)

RESULTS
Literature Search and Study 

Characteristics Results 

• Literature search:

• Identified 884 titles; 92 full-text reviews

• 23 included reports of 16 unique trials

• Study characteristics: 

• All US-based studies

• 10 trials DID NOT used depression as inclusion criteria (used 

subgroup analysis from these trials) 

• Most tested combo treatment 

(e.g., counseling + pharmacotherapy)

• Most common counseling type = CBT

• One telephone-delivered study
Key Question 1 Results 

For patients with a history of a depressive disorder 

or current significant depressive symptoms, what is 

the comparative effectiveness of different smoking 

cessation strategies on smoking abstinence rates?
Results: Nicotine Replacement 

Therapy 

Study, 

year

Sample size

(% depressed)

Intervention Arm Comparator Improved

smoking 

cessation?

Kinnunen, 

1996

269

(34% met 

criteria for 

depression)

Nicotine gum + one-time brief 

individual behavioral counseling 

Placebo gum + one-time brief 

individual behavioral 

counseling YES

Kinnunen, 

2008

608

(32% met 

criteria for 

depression)

Nicotine gum + 9 brief in-person 

individual counseling sessions 

Placebo gum + 9 brief inperson individual counseling 

sessions YES

Hall, 1996 201

(22% MDD 

history 

positive)

Nicotine gum + 10 sessions of 

group CBT smoking cessation 

counseling or 10 session health 

education 

Placebo gum + 10 sessions of 

group CBT smoking cessation 

counseling or 10 sessions 

health education 

NO

Hall, 2006 322

(100% with 

current 

depression)

Transdermal nicotine patch (or 

bupropion if failed NRT) + staged 

motivational feedback + 6 

sessions of individual CBT 

Brief contact with self-help 

guide + list of referrals to 

smoking cessation programs 

and stop smoking guide

YES
Results: Antidepressant 

Study or Subgroup Hayford 1999 Hall 1998b Covey 2002

Total (95% CI) Total events Heterogeneity: Tau2 = 0.00; Chi2 = 0.55, df = 2 (P = 0.76); I2 = 0%

Test for overall effect: Z = 0.90 (P = 0.37)

Events

4

7

11

22

Total

28

32

66

126

Events

2

7

8

17

Total

28

33

68

129

Weight

13.0%

39.4%

47.5%

100.0%

M-H, Random, 95% CI

2.00 [0.40, 10.05] 1.03 [0.41, 2.61] 1.42 [0.61, 3.30]

1.31 [0.73, 2.34]

Antidepressant Placebo Risk Ratio Risk Ratio M-H, Random, 95% CI

0.05 0.2 1 5 20 Favours control Favours antidepressant

Risk of smoking abstinence at least 6 months after start of 

antidepressant therapy + behavioral counseling vs. 

placebo + behavioral counseling
Results: Antidepressants 

Study, 

year

Sample size

(% depressed)

Intervention Arm Comparator Improved

smoking 

cessation?

Evins, 

2008

199

(100% MDD

history 

positive)

Bupropion + 13 group CBT 

smoking cessation 

counseling + NRT patch 

Placebo + 13 group CBT 

smoking cessation 

counseling + NRT patch NO

Saules, 

2004

150

(20% MDD

history 

positive)

Fluoxetine + 6 group CBT 

smoking cessation 

counseling + NRT patch 

Placebo + 6 group CBT 

smoking cessation 

counseling + NRT patch NO
Results: Mood Management 

Therapy 

Risk of smoking abstinence at least 6 months after start of mood management 

therapy + cotreatment compared to active control 

Study or Subgroup

NRT or Antidepressant

MacPherson 2010

Hall 1994

Hall 1996a

Hall 1998a

Subtotal (95% CI)

Total events

Heterogeneity: Tau2 = 0.00; Chi2 = 1.80, df = 3 (P = 0.62); I2 = 0%

Test for overall effect: Z = 1.79 (P = 0.07)

No NRT or Antidepressant

Brown 2001

Subtotal (95% CI)

Total events

Heterogeneity: Not applicable

Test for overall effect: Z = 1.15 (P = 0.25)

Total (95% CI)

Total events

Heterogeneity: Tau2 = 0.00; Chi2 = 2.16, df = 4 (P = 0.71); I2 = 0%

Test for overall effect: Z = 2.03 (P = 0.04)

Events

5

10

7

9

31

28

28

59

Total

35

29

21

34

119

86

86

205

Events

0

4

5

5

14

23

23

37

Total

33

17

23

31

104

93

93

197

Weight

1.6%

13.0%

13.3%

13.4%

41.2%

58.8%

58.8%

100.0%

M-H, Random, 95% CI

10.39 [0.60, 180.84]

1.47 [0.54, 3.96]

1.53 [0.57, 4.10]

1.64 [0.62, 4.37]

1.66 [0.95, 2.90]

1.32 [0.83, 2.10]

1.32 [0.83, 2.10]

1.45 [1.01, 2.07]

Mood Management Control Risk Ratio Risk Ratio

M-H, Random, 95% CI

0.05 0.2 1 5 20

Favours control Favours mood management
Results: Mood Management 

Therapy 

Study, year Sample size

(% depressed)

Intervention Arm Comparator Improved

smoking 

cessation?

Duffy, 

2006

184

(35% depressed 

smokers)

9 to 11 session of 

combined smoking, 

depression, alcohol 

abuse telephone CBT + 

bupropion + NRT (if 

failed bupropion 

monotherapy in the 

past) OR NRT + 

paroxetine (if failed 

bupropion in the past 

for depression)

One-time behavioral 

counseling and referral 

to appropriate services 

for substance 

use/abuse and/or 

depression

Yes
Results: Other Strategies 

Study, year Sample size

(% depressed)

Intervention Arm Comparator Improved

smoking 

cessation?

Covey, 1999 80

(45% MDD history 

positive)

Naltrexone + 6 individual 

in-person behavioral 

counseling sessions 

Placebo + 6 individual inperson behavioral 

counseling sessions

YES

Munoz, 

1997

136

(78% MDE history 

positive)

Mailed smoking cessation 

guide + mood 

management guide 

Mailed smoking cessation 

guide + mood 

management guide at 3 

months delayed

YES

Vickers, 

2009

60

(100% with current 

depression)

10 in-person individual 

exercise counseling 

sessions that include brief 

smoking cessation 

counseling + NRT 

10 in-person individual 

health education sessions 

that include brief smoking 

cessation counseling + NRT

NO
Key Question 2 Results 

For patients with a history of a depressive disorder 

or current significant depressive symptoms, are 

there differential effects of smoking cessation 

strategies by depression status (i.e., history of 

MDD, current depressive symptoms, current 

MDD)?
Results: Depression Status 

Moderation

Study, year Intervention Arm Comparator Improved smoking 

cessation?

Evins, 2008 Bupropion + 13 group 

CBT smoking cessation 

counseling + NRT patch 

Placebo + 13 group CBT 

smoking cessation 

counseling + NRT patch 

MDD Hx positive (NO)

Current depression (NO)

Munoz, 

1997

Mailed smoking 

cessation guide + mood 

management guide 

Mailed smoking cessation 

guide + mood management 

guide at 3 months delayed

MDD Hx positive (YES)

Current MDD (NO)
Key Question 3 Results 

For patients with a history of a depressive disorder 

or current significant depressive symptoms, are 

there differential effects of smoking cessation 

strategies by gender? 
Key Question 4 Results 

For patients with a history of a depressive disorder 

or current significant depressive symptoms, does 

treatment effectiveness differ by whether smoking 

cessation/depression treatments are delivered 

concurrently or sequentially?
Key Question 5 Results 

For patients with a history of a depressive disorder 

or current significant depressive symptoms, what is 

the nature and frequency of adverse effects of 

smoking cessation treatments?
Adverse Effect Results 

Study, year Intervention

Adverse effects reported

(% reported in intervention versus control)

Covey, 1999

Naltrexone + 6 individual in-person 

behavioral counseling sessions Panic attack, malaise, sleeplessness, concentration difficulty, 

nausea and vomiting, disoriented and shaky, spaciness, dizzy, 

abdominal pain, lightheadedness, shortness of breath

Hall, 1998

5 group sessions of CBT mood 

management + 5 group sessions of 

smoking cessation counseling + 

nortriptyline

Dry mouth (78% vs 33%), lightheadedness (49% vs 22%) 

shaky hands (23% vs 11%) blurry vision (16% vs 6%)

Hayford, 1999

Bupropion + 11 brief in-person individual 

counseling sessions Headache (29% vs 31-33%) insomnia (21% vs 30-35%)

rhinitis (17% vs 10 to 12%)

dry mouth (5% vs 13%)

increased anxiety (11% vs 5-7%)

Kinnunen, 2008

Nicotine gum + 9 brief in-person individual 

counseling sessions Heart palpitations, nausea, vomiting, dizziness, breathing 

difficulties, tongue blisters, damage to dental work, sore jaw

Saules, 2004

Fluoxetine + 6 group sessions of CBT 

smoking cessation counseling + NRT patch

Adverse effects not more common in intervention arms but 

did not list types
Limitations

• Broad intervention categories 

• Few trials recruited depressed smokers

• Use of subgroup data

• Limited data on many KQs

• Few trials with VA users
Summary & Discussion 

• Few trials 

• Limited data on important treatment moderators

• Behavioral mood management therapy = small positive effect 

• Antidepressants use = insufficient evidence 

• NRT = small positive effect 

Bottom line: 

Patients with depression can quit smoking.
Evidence-based Synthesis Program 

(ESP)

Questions?

If you have further questions, 

feel free to contact:

Jennifer M. Gierisch

Email: j.gierisch@duke.edu or jennifer.gierisch@va.gov

Telephone: (919) 286-0411 X 5655

The full report and cyberseminar presentation is available on the ESP website: 

http://www.hsrd.research.va.gov/publications/esp/