Evidence-based Synthesis Program 

Comparative Effectiveness

of Smoking Cessation Treatments

for Patients With Depression:

A Systematic Review and

Meta-analysis of the Evidence

Department of Veterans Affairs

Health Services Research & Development Service

November 2010

Investigators: 

Principal Investigator: 

Jennifer M. Gierisch, PhD, MPH 

Coinvestigators:

Lori A. Bastian, MD, MHSc 

Patrick S. Calhoun, PhD 

Jennifer R. McDuffie, PhD

John W. Williams, Jr., MD, MHSc 

Medical Editor: 

Liz Wing, MA

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Durham VA Medical Center 

Durham, NC

John Williams, Jr., MD, MHSc, Director
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Comparative Effectiveness of Smoking Cessation Treatments 

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PREFACE

HSR&D’s Evidence-based Synthesis Program (ESP) was established to provide timely and 

accurate syntheses of targeted healthcare topics of particular importance to VA managers 

and policymakers, as they work to improve the health and healthcare of Veterans. The ESP 

disseminates these reports throughout VA. 

HSR&D provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help: 

• develop clinical policies informed by evidence, 

• the implementation of effective services to improve patient outcomes and 

to support VA clinical practice guidelines and performance measures, and 

• set the direction for future research to address gaps in clinical knowledge.

In 2009, an ESP Coordinating Center was created to expand the capacity of HSR&D Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of HSR&D field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and VISN Clinical Management 

Officers. The Steering Committee provides program oversight and guides strategic planning, 

coordinates dissemination activities, and develops collaborations with VA leadership to identify 

new ESP topics of importance to Veterans and the VA healthcare system. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP

Coordinating Center Program Manager, at nicole.floyd@va.gov. 

Recommended citation: Gierisch JM, Bastian LA, Calhoun PS, McDuffie JR, Williams JW Jr. 

Comparative Effectiveness of Smoking Cessation Treatments for Patients With Depression: A 

Systematic Review and Meta-analysis of the Evidence. VA-ESP Project #09-010; 2010 

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. 
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Comparative Effectiveness of Smoking Cessation Treatments 

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TABLE OF CONTENTS

Executive Summary.............................................................................................................................................

Background .......................................................................................................................................................1

Methods.............................................................................................................................................................2

Results...............................................................................................................................................................2

Key Question 1..................................................................................................................................................2

Key Question 2..................................................................................................................................................2

Key Question 3..................................................................................................................................................3

Key Question 4..................................................................................................................................................3

Key Question 5..................................................................................................................................................3

Future Research Recommendations .................................................................................................................3

Conclusions.......................................................................................................................................................4

Introduction .......................................................................................................................................................... 

Methods..................................................................................................................................................................

Topic Development...........................................................................................................................................6

Search Strategy .................................................................................................................................................7

Study Selection .................................................................................................................................................7

Data Abstraction................................................................................................................................................8

Quality Assessment...........................................................................................................................................8

Data Synthesis...................................................................................................................................................9

Peer Review ....................................................................................................................................................10

Results ..................................................................................................................................................................

Literature Search and Study Characteristics................................................................................................... 11

Key Question 1................................................................................................................................................13

Key Question 2................................................................................................................................................21

Key Question 3................................................................................................................................................22

Key Question 4................................................................................................................................................22

Key Question 5................................................................................................................................................22

Discussion.............................................................................................................................................................

Summary and Discussion................................................................................................................................25

Strengths and Limitations...............................................................................................................................26

Conclusions.....................................................................................................................................................27
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Comparative Effectiveness of Smoking Cessation Treatments 

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Future Research..............................................................................................................................................

References........................................................................................................................................................

Appendix A: Search Strategy.....................................................................................................................

Appendix B: Reviewer Comments and Responses......................................................................

Appendix C: Evidence Table.....................................................................................................................

List of Included Studies..................................................................................................................................70

Appendix D: Excluded Studies ..................................................................................................................

List of Excluded Studies.................................................................................................................................74

Appendix E: Acronyms and Abbreviations.........................................................................................

Figur

Figure 1. Analytic Framework ........................................................................................................................7

Figure 2. Literature Flow Diagram ............................................................................................................... 11

Figure 3. Risk of Smoking Cessation at Least 6 Months After Start of Antidepressant Therapy

Plus Behavioral Counseling Compared With Placebo + Behavioral Counseling.........................16

Figure 4. Risk of Smoking Cessation at Least 6 Months After Start of Mood Management Treatment Plus 

Cotreatment Compared to Active Control.....................................................................................19

Ta

Table 1. Summary of Inclusion and Exclusion Criteria ................................................................................8

Table 2. Definitions for Strength of Evidence Rating .................................................................................10

Table 3. Summary of Study Characteristics................................................................................................12

Table 4. Smoking Cessation Studies of NRT Plus Brief Counseling Versus Placebo Plus Brief

Counseling .....................................................................................................................................14

Table 5. Smoking Cessation Studies of NRT Plus Behavioral Counseling Versus Active Control............15

Table 6. Smoking Cessation Studies of Antidepressant Therapy Plus Behavioral Counseling Versus

Placebo Plus Behavioral Counseling.............................................................................................15

Table 7. Smoking Cessation Studies of Antidepressant Therapy Plus Behavioral Counseling Plus NRT 

Versus Placebo Plus Behavioral Counseling Plus NRT ................................................................16

Table 8. Smoking Cessation Studies With a Mood Management Treatment Component..........................17

Table 9. Other Smoking Cessation Intervention Strategies Studies............................................................21

Table 10. Adverse Effects of Included Studies..............................................................................................23

Table 11. Summary of the Strength of Evidence for Key Questions 1 to 5..................................................28

Table 12. List of Excluded Studies................................................................................................................71 
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Comparative Effectiveness of Smoking Cessation Treatments 

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EXECUTIVE SUMMARY

BACKGROUND

Smoking is disproportionately higher among persons with depression (45% versus 22%). 

Furthermore, smokers with depression may experience more challenges when trying to make 

and maintain a quit attempt, such as greater negative mood symptoms from withdrawal, higher 

nicotine dependence, and greater likelihood of relapse, than smokers without depression. Despite 

the complex relationship between tobacco use and depression, smokers with depression are 

motivated to quit smoking and should be offered cessation services. Several evidence-based 

smoking cessation treatments are effective for the general population of smokers. Yet the 

comparative effectiveness of these strategies in smokers with depression is uncertain. Also, it is 

uncertain if factors that may facilitate targeted interventions, such as depression status, gender, 

and treatment sequencing (i.e., concurrent versus sequential) for mood and smoking cessation, 

differentially impact the effectiveness of smoking cessation interventions. We conducted a 

systematic review of the peer-reviewed literature to answer the following key questions:

Key Question 1: 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?

Key Question 2: 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)?

Key Question 3: 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: 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: What is the nature and frequency of adverse effects of smoking cessation 

treatments in patients with a history of a depressive disorder or current significant depressive 

symptoms?

This review was commissioned by the Department of Veterans Affairs’ Evidence-based Synthesis 

Program. The topic was selected after a formal topic nomination and prioritization process that 

included representatives from the Office of Mental Health Services, Health Services Research 

and Development, the Mental Health QUERI, and the Office of Mental Health and Primary 

Care Integration. The key research questions for this review were developed and refined after 

preliminary review of published peer-reviewed literature and consultation with VA and non-VA 

experts to select the patients and subgroups, interventions, outcomes, and settings addressed in 

this review. 
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Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

METHODS

We searched for English-language publications in MEDLINE® (via PubMed®), Embase®, 

PsycINFO®, and the Cochrane Library from database inception through March 10, 2010. We 

developed search strategies in consultation with a master librarian. Titles, abstracts, and articles 

were reviewed in duplicate by trained researchers. A trained researcher abstracted data from 

published reports into evidence tables; a second reviewer overread the evidence tables. When 

study designs and outcomes reported were similar, we estimated pooled risk ratios (RR) with 

95% confidence intervals (CI) by using a random effects model with the Mantel-Haenszel 

method. For these analyses, we classified each intervention element into the following categories: 

antidepressants, nicotine replacement therapy (NRT), brief smoking cessation counseling, 

behavioral counseling for smoking cessation, or behavioral mood management treatment. All 

other data were narratively summarized.

RESULTS

We screened 884 titles, rejected 792, and performed full-text reviews on 92 articles. We manually 

pulled 6 additional papers in order to retrieve supplemental methodological or background 

information on studies included in the full-text review. Of these 98 papers, we excluded 75. The 

23 included reports encompassed 16 unique trials, of which only three recruited participants with 

current depression. 

Key Question 1: 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?

We identified three types of intervention strategies: cotreatments augmented with behavioral 

mood management treatment (six trials), cotreatments augmented with antidepressant therapy 

(five trials), and cotreatments augmented with NRT (four trials). Cotreatments generally 

consisted of some type of smoking cessation counseling (e.g., brief, behavioral), with or without 

NRT. We also identified three additional trials that used exercise behavioral counseling plus 

NRT, mailed self-help materials, or long-acting opiate antagonist plus behavioral counseling as 

smoking cessation interventions.

Pooled results from our meta-analysis demonstrate a small, positive effect of adding behavioral 

mood management treatments to smoking cessation cotreatments (RR = 1.45, 95% CI 1.01 to 

2.07). All of the included antidepressant trials showed small, positive effects when comparing 

antidepressants plus behavioral counseling to placebo plus behavioral counseling, but a summary 

estimate of effect from meta-analysis was not statistically significant (RR = 1.31, 95% CI 0.73 

to 2.34). We were unable to conduct a meta-analysis of NRT trials. Three of the four NRT trials 

showed positive effects with clinically significant abstinence. Two of these NRT trials reported 

statistically significant differences. Results from three of the four included studies suggest that 

offering NRT appears to have a small, positive effect on smoking cessation rates among smokers 

who are depressed. We found insufficient evidence to support exercise behavioral counseling, 

mailed self-help materials, or naltrexone, although both naltrexone and mailed self-help materials 

showed positive effects in single trials. 

Key Question 2: For patients with a history of a depressive disorder or current significant 

depressive symptoms, are there differential effects of smoking cessation strategies by depression 
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status (i.e., history of MDD, current depressive symptoms, current MDD)?

Only two studies provided information on differential effectiveness of smoking cessation 

intervention strategies by depression status. Study researchers conducted subgroup analysis 

only; no treatment by depression interaction effects were directly tested. Among participants 

who were history positive for unipolar depression in Evins (2008), 39% in the bupropion plus 

behavioral counseling plus NRT arm and 32% in the placebo plus behavioral counseling plus 

NRT control arm were abstinent at the end of trial (p-value NS). Bupropion did not significantly 

improve smoking cessation rates compared to active control condition for participants with 

current depression (33% versus 31%; p-value NS). In Munoz and colleagues (1997), the addition 

of mailed mood management content improved cessation rates over a mailed smoking cessation 

guide (38.5% versus 7.4%; p = 0.01) at 6 months postrandomization for participants with a 

history of major depressive episode (MDE). Smokers with current MDE did not experience 

significant differences (17.9% versus 8.0%; p = 0.15).

Key Question 3: For patients with a history of a depressive disorder or current significant 

depressive symptoms, are there differential effects of smoking cessation strategies by gender? 

Only one included study reported a significant treatment by gender interaction among study 

participants with a history of or current depression. Covey and colleagues (1999) found a 

significant treatment by gender by depression interaction. Women with past histories of MDD 

experienced higher quit rates when randomized to receive naltrexone in combination with six 

sessions of individual behavioral counseling compared to women with depression receiving 

placebo control at 6 months. Men who were MDD history positive did not have higher quit rates 

on naltrexone.

Key Question 4: 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? 

No studies directly compared smoking cessation and depression treatments delivered 

concurrently versus sequentially.

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

treatments in patients with a history of a depressive disorder or current significant depressive 

symptoms?

Most included trials did not provide information on the nature and frequency of adverse effects 

of treatments. Of the five studies that reported adverse effects, three provided some level of detail 

about the magnitude and significance of adverse effects. These three studies all evaluated the 

addition of antidepressants with other smoking cessation treatments. In two of the three studies, 

selected adverse effects were more common in patients randomized to antidepressants compared 

to placebo control.

FUTURE RESEARCH RECOMMENDATIONS

While this review provided some evidence of smoking cessation strategies for patients with 

depression, more work is needed in this area. Principally, we found very little trial data on 

intervening with smokers with current depression. Future studies should be designed to test 

smoking cessation interventions for this vulnerable population. Next, within the trials we 
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identified, we found little research on key moderators that may influence treatment effectiveness 

(e.g., gender, depression status). Moderator analysis will facilitate subgroup identification 

and may lead to better treatment matching. In many instances, we were able to address only 

the incremental benefit of adding one strategy to an intervention package (e.g., behavioral 

counseling with or without antidepressant). Future studies should be designed to allow for direct 

comparisons between combinations of likely efficacious therapies for smokers with depression 

such as combination NRT therapy. Also, we were unable to disaggregate multicomponent 

interventions. Future research should be designed to disentangle active ingredients of 

interventions and optimize dose, duration, frequency, and sequencing of smoking cessation 

strategies. Finally, future research should be conducted to characterize adverse effects of 

treatments, including changes in negative affect and depressive symptoms.

CONCLUSIONS

In conclusion, the peer-reviewed literature contained few randomized controlled trials of 

smoking cessation interventions for patients with depression. Most trials excluded patients with 

current or recent MDD. Thus, most of the data for this evidence review were from subgroup 

analyses of patients with depressive symptoms or remote histories of depressive disorder. 

However, the majority of reports included in this evidence review were of good quality and had 

consistent results. We found insufficient evidence to characterize adverse effects of treatments 

and examine moderator effects of gender, depression status, and treatment delivery sequencing. 

However, this evidence review lends support for several promising interventions. Our results 

support a small, positive effect for adding behavioral mood management counseling to smoking 

cessation cotreatments. Smokers with depression may respond better to smoking cessation 

interventions augmented with mood management techniques. Evidence also shows support 

for adding NRT; however, included trials were too varied to be analyzed quantitatively. All of 

the included antidepressant trials showed small, positive effects, but a summary estimate of 

effect was not statistically significant. However, there was heterogeneity in antidepressant type 

across studies. Effects likely vary with medication type. Health care providers should consider 

encouraging their patients with depression who smoke to seek smoking cessation services that 

include NRT and also address behavioral mood management counseling.
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EVIDENCE REPORT

INTRODUCTION

Tobacco smoking is the single greatest preventable cause of disease in the United States.1,2 Half 

of all American smokers who fail to quit will die of a smoking-related illness.3

 Cigarette use 

is higher among Americans with depression than in the general U.S. population.4

 Persons with 

depression are about twice as likely (45% versus 22%) to be current smokers than are individuals 

who are not depressed,5 and smokers are more likely to have a history of depression.6,7 Moreover, 

veterans have higher rates of depression and smoking compared to the general population.8-12

Several hypotheses have been offered to explicate the association between smoking and 

depression, including mood-enhancing effects of nicotine13,14 and common genetic and 

environmental factors. Depression also appears to be an important factor in smoking 

cessation.15-20 Smokers who are depressed are more likely to relapse from a quit attempt, have 

higher nicotine dependence, suffer negative mood symptoms from withdrawal, and suffer greater 

smoking-related morbidity and mortality than the general population of smokers.17,18,21-24

Smokers with depression are highly motivated to quit smoking.7,25 One study found that 79% 

of smokers with depression intended to quit, with 24% ready to make a quit attempt in the 

next month.26 Despite the complex relationship between tobacco use and depression, smokers 

with depression should be offered cessation services.27,28 Several evidence-based smoking 

cessation intervention strategies exist for the general population of smokers.29-35 All forms of 

nicotine replacement therapy (NRT) (e.g., gum, transdermal patch, inhaler, lozenges) augment 

successful quit attempts, increasing quit rates by as much as 50 to 70%.35 Also, use of some 

antidepressants (i.e., bupropion, nortriptyline) can double the chances of smoking cessation, 

and this effect seems independent of the antidepressive effects of these medications.36 For 

behavioral interventions, there is a strong dose-response relationship between treatment intensity 

and smoking cessation rates.37 More intensive interventions, measured by total contact time, are 

associated with increased abstinence rates. For example, smoking cessation counseling improves 

quit attempts over self-help aids and other less intensive therapies.29,33,34,38 Combining behavioral 

interventions with pharmacotherapy increases quit attempts over each therapy delivered alone 

and is considered the gold standard of care for effective smoking cessation treatment.29,37,39

Gender, depression status (e.g., history positive, depression symptom severity), and content 

delivery timing (i.e., sequential, concurrent) may differentially impact the effectiveness 

of smoking cessation intervention efforts for smokers with depression. When trying to 

quit smoking, women who are depressed may experience more difficulty with withdrawal 

symptoms and, consequently, higher rates of smoking relapse to alleviate withdrawal symptoms 

compared to their male smoker counterparts.40 Level of depressive symptoms or depression 

type may influence patients’ ability to make and maintain quit attempts.17,18,22 Also, smokers 

with depression may benefit from smoking cessation programs that target both depression 

symptoms and tobacco use. However, it is not known if these two conditions should be treated 

concurrently or sequentially. For example, it is not known if treating depression first influences 

smoking cessation treatment effectiveness. Treating depression first may lead to greater 

treatment adherence and, consequently, better cessation rates. It is plausible but unstudied. 

Smokers with psychiatric comorbidities may benefit from combined behavioral counseling and 
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pharmacotherapy with longer therapeutic smoking cessation approaches (i.e., exceeding 8 to 

12 weeks) to reduce likelihood of dropout and depression relapse.27,41 However, no systematic 

reviews have synthesized the comparative effectiveness of smoking cessation strategies for 

persons with depressive symptoms. Many unanswered questions remain about how effective 

smoking cessation interventions are for adults with depression.

METHODS

Top

This review was commissioned by the Department of Veterans Affairs’ Evidence-based Synthesis 

Program. The topic was selected after a formal topic nomination and prioritization process that 

included representatives from the Office of Mental Health Services, Health Services Research 

and Development, the Mental Health QUERI, and the Office of Mental Health and Primary 

Care Integration. The key research questions for this review were developed and refined after 

preliminary review of published peer-reviewed literature and consultation with VA and non-VA 

experts to select the patients and subgroups, interventions, outcomes, and settings addressed in 

this review. 

The final key questions were as follows: 

Key Question 1: 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?

Key Question 2: 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)?

Key Question 3: 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: 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: What is the nature and frequency of adverse effects of smoking cessation 

treatments in patients with a history of a depressive disorder or current significant depressive 

symptoms?

We developed and followed a standard protocol for all steps of this review. Our approach was 

guided by the analytic framework shown in Figure 1.
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Comparative Effectiveness of Smoking Cessation Treatments 

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Figure 1. Analytic Framework

Sea

We searched for English-language publications in MEDLINE (via PubMed), Embase, 

PsycINFO, and the Cochrane Library from database inception through March 10, 2010. We 

developed search strategies in consultation with a master librarian. The search terms and MeSH 

headings for the search strategies appear in Appendix A. We supplemented electronic searching 

by examining the bibliographies of included studies.

Stu

Using prespecified inclusion/exclusion criteria, two trained researchers reviewed the list of 

titles and selected articles for further review. Each article retrieved was reviewed with a brief 

screening form used to determine eligibility. To be included in our evidence report, a study 

had to (1) be a randomized controlled trial (RCT), (2) compare two or more smoking cessation 

interventions or compare intervention to control, and (3) report smoking cessation outcomes in 

adults with depression. Detailed eligibility criteria are described in Table 1. 

Adverse effects of

treatment

Adult 

smokers 

with 

depressive 

symptoms

Patient-level smoking 

cessation strategies alone

or in combination with

other strategies

• Depression status (KQ 2)

• Gender (KQ 3)

• Treatment sequencing (KQ 4)

Smoking abstinence

(KQs 1-5) (KQ 5)

(KQ 1)
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Table 1. Summary of Inclusion and Exclusion Criteria

Study 

characteristic Inclusion criteria Exclusion criteria

Study design RCTs or a secondary data analysis from 

RCTs of smoking cessation interventions 

Non-English language publication, crosssectional studies

Population Adults age 18 and over with a history of a 

depressive disorder or current significant 

depressive symptomsa

Pregnant women, adolescents, postpartum depression, depressive symptoms 

secondary to another primary condition 

(e.g., substance abuse, schizophrenia)

Interventions Any patient-level smoking cessation strategies (e.g., self-help, quit lines, physician or 

brief advice, behavioral counseling, pharmacologic therapies) alone or in combination 

with other strategies

Policy-level interventions (e.g., smoking 

bans), mass media campaigns

Comparators Active comparators or control (e.g., usual 

care or placebo)

None

Setting Outpatient (e.g., mental health clinics, 

primary care) or delivered through remote 

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

Hospital-based (inpatient) interventions 

Outcome KQs 1-4: Smoking abstinence reported at ≥ 

3 months postrandomization

KQ 5: Adverse effects including behavioral 

symptoms, increased anxiety, depressionb

Relapse preventionc 

a We define significant depressive symptoms as meeting a designated threshold on a validated assessment instrument (e.g., 

CES-D, BDI). 

b We considered depression as an adverse effect when participants moved from depressive symptoms to a depressive disorder, 

or when the intervention arm showed significantly more depressive symptoms compared to a decrease in symptoms in the 

comparator condition.

c Intervention strategies that reduce the likelihood of recent quitters returning to smoking.

Abbreviations: BDI = Beck Depression Inventory, CES-D = Center for Epidemiologic Studies-Depression Scale, RCT = 

randomized controlled trial

Dat

A trained researcher abstracted data from published reports into evidence tables; a second 

reviewer overread the evidence tables. We resolved disagreements by consensus among the 

first and second reviewer or by obtaining a third reviewer’s opinion when consensus could 

not be reached. We abstracted the following data from included studies: (1) Study design and 

setting, (2) eligibility criteria, (3) exclusion criteria, (4) sample size, (5) demographics, (6) 

duration of follow-up, (7) depression clinical category, (8) baseline smoking characteristics (e.g., 

cigarettes per day, tobacco dependence), (9) method used to assess depression, (10) intervention 

characteristics (e.g., mode, frequency, dose, core therapy components), (11) outcome measures, 

(12) results, and (13) adverse effects. 

Qua

We assessed risk of bias using the key quality criteria described in the Agency for Healthcare 

Research and Quality (AHRQ) Methods Guide for Effectiveness and Comparative Effectiveness 

Reviews (hereafter referred to as the General Methods Guide),

42 adapted for this specific topic. 

We abstracted data on adequacy of randomization and allocation concealment, comparability 
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of groups at baseline, blinding, completeness of follow-up and differential loss to follow-up, 

whether incomplete data were addressed appropriately, validity of outcome measures, and 

conflict of interest. Using these data elements, we assigned a summary quality score of Good, 

Fair, or Poor to individual RCTs.

Dat

We constructed evidence tables showing the study characteristics and results for all included 

studies, organized by key question and intervention, as appropriate. We critically analyzed 

studies to compare their characteristics, methods, and findings. We compiled a summary of 

findings for each key question. 

When study designs and outcomes reported were similar, we estimated pooled risk ratios with 

95% confidence intervals (CIs) by using a random effects model with the Mantel-Haenszel 

method. For these analyses, we classified each intervention element into the following categories: 

Antidepressants, nicotine replacement therapy (NRT), brief smoking cessation counseling, 

behavioral counseling for smoking cessation, or behavioral mood management treatment. We 

defined brief smoking cessation counseling as counseling that was similar in content to what may 

be given during a physician visit. We defined behavioral counseling for smoking cessation as 

multisession individual or group therapy that used behavioral strategies, such as those common 

in cognitive behavioral therapy (CBT), to influence tobacco use. Behavioral mood management 

treatment was defined as group or individual counseling intended to influence negative mood and 

improve depression symptomatology above and beyond standard smoking cessation counseling. 

Using these intervention categories, there were sufficient studies to perform meta-analyses for 

two comparisons: Mood management versus control and antidepressants versus control. Other 

comparisons were synthesized qualitatively. All studies that were analyzed quantitatively used 

behavioral counseling for smoking cessation in the intervention and control arms. For the mood 

management comparison, we subgrouped studies using NRT alone or in combination with 

antidepressants. 

The primary outcome was smoking abstinence without smoking relapse. Smoking abstinence 

was defined as smoking cessation collected as (1) point prevalence abstinence (e.g., in past 7 

days) or (2) extended abstinence (e.g., since quit date or last previous follow-up). We included 

only one effect size per study. Therefore, we assessed the most distal and rigorous (extended 

abstinence over point prevalence) outcomes reported and categorized as short-term (3 < 6 

months) or long-term (≥ 6 months) confirmed by self-report, biochemical validation, or both. 

Our outcome was informed by outcomes used in the Cochrane Collaborative reviews, which are 

based on the Russell Standard.43 The U.S. Department of Health and Human Services Tobacco 

Use and Dependence Guideline Panel recommended a minimum of a 6-month period to assess 

treatment differences in the longer term.37 Therefore, we used 6 months or longer outcomes for 

meta-analyses. Abstinence could be assessed by self-report or with biochemical verification. 

Two studies44,45 used a factorial design to compare pharmacological and behavioral interventions; 

these comparisons were treated as separate studies in the analyses. We evaluated heterogeneity 

visually and with the Cochran Q statistic46 using a threshold p-value of less than 0.1047 and the 

I2

 statistic.48 We considered I2 statistic thresholds of 0% to 40%, 30% to 60%, 50% to 90%, and 

75% to 100% to represent between-study heterogeneity that might not be important, moderate, 
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substantial, or considerable, respectively.49 We planned a priori to conduct subgroup analyses by 

depression status (severity and specific diagnosis), gender, and treatment sequencing, but there 

were not sufficient studies to conduct these analyses. All analyses were performed using Review 

Manager 5.0 software (The Cochrane Collaboration, Oxford).

Grading the Evidence for Each Key Question 

We graded the strength of evidence for each key question using the principles from the 

GRADE Working Group.50 In brief, this approach assesses the strength of evidence for each 

critical outcome by considering risk of bias, consistency, directness, precision, and publication 

bias. Other domains relevant to observational designs were not pertinent to our review. After 

considering each domain, a summary rating of High, Moderate, Low, or Insufficient strength of 

evidence was assigned after discussion by two reviewers (Table 2).

Table 2. Definitions for Strength of Evidence Rating

Strength of evidence 

rating Definition

High quality Further research is very unlikely to change our confidence in the 

estimate of effect

Moderate quality Further research is likely to have an important impact on our 

confidence in the estimate of effect and may change the estimate

Low quality

Further research is very likely to have an important impact on our 

confidence in the estimate of effect and is likely to change the 

estimate

Insufficient Evidence on an outcome is absent or too weak, sparse or 

inconsistent to estimate an effect

Peer

Peer reviewer comments and our responses are presented in Appendix B.
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RESULTS

Liteatu

The combined literature search of PubMed, Embase, PsycINFO, and Cochrane databases, minus 

duplicates, contained 884 unique citations, of which we excluded 792 after reviewing titles and 

abstracts. We then conducted full-text reviews of 92 articles and pulled 6 additional papers in 

order to retrieve supplemental methodological or background information on studies included 

in the full-text review. Of these 98 papers, we excluded 75. Figure 2 summarizes the literature 

flow. The 23 included reports encompassed 16 unique trials with a total of 3,553 depressed and 

nondepressed participants. Table 3 summarizes study characteristics. In studies that included 

depressed and nondepressed participants, we report information for the depressed subgroup when 

available.

Figure 2. Literature Flow Diagram

6 articles from included 

studies retrieved for 

additional information

75 articles excluded at full-text review:

•	 Population not depressed = 37

•	 Main outcome not of interest = 14

•	 Not peer reviewed = 7

•	 Main outcome not reported at 

desired interval = 6

•	 Not RCT or secondary analysis of 

RCT = 6

•	 Analysis did not address key 

questions = 5

Articles retrieved 

for full-text review 

= 92

Search results 

= 884

Abstracted 23 

reports of 16 

unique trials

792 articles excluded 

at abstract screening
12

moking Cessation Treatments 

Evidence-based Synthesis Program

haracteristics

Sample size Age Mean (SD) % Female % White FTND Mean (SD) Cigarettes per day Mean (SD) Depressed mood at baseline Mean (SD

79 All MDD history positive 45.1 (9.3) 59.8 97.2 6.8 (1.9) NR BDI: 7.8 (6.31)

05% MDD history positive 33.8b (8.2) 68.0b NR NR 30.3 (10.1) NR34 All MDD history positive 44.5 (10.7) 63.4 87.3 6.1(2.4)b NR BDI: 8.0 (7.7) CES-D: 14.9 (10.8) HDRS: 4.8 (4.4)84 5% depressed smokers 57.0 (9.9) 16.0 90.0 NR NR NR99 All MDD history positive 43.0 (11.0) 49.0 NR 5.8 (2.2) 25.0 (11) HDRS: 10.6 (6.3) 49 1% MDD history positive 40.6 (9.2) 52.0 88.0 6.4 (1.9) 24.9 (10.9) BDI: 6.4 (5.9)c

01 2% MDD history positive 39.7 (NR) 52.0 92.0 NR 23.8 (9.8) BDI: 6.7 (5.4)99 3% MDD history positive 41.9c (9.9) 42.0c 59.0c 5.5 (2.2)c 21.8 (10.4)c BDI: 12.1 (8.3)c22 All with current depression 41.5 b (12.4) 69.6 68.3 3.8 (2.4) 15.8 (10.0) BDI: 20.6 (11.7)b15 9% MDD history positive 42.2 – 43.7d 54.6 96 FTQ: 7.1-7.3 (1.7) d 26.2(8.5) – 27.5(9.6)d BDI: 4.1(4.2) –4.7 (5.0) d69 4% met criteria for depression 40.4 (12.6) 41.6c (12.7) 51.0 61.0c 82.0 80.0c 5.6 (2.4)c 22 (10.4)c NR

08 2% met criteria for depression 38.5 (11.3)c 51.0c 78.6c Women: 5.6(2.3)c Men: 6.2 (2.3)c Women: 21.0(10.0)c men:26.6(11.7)c CES-D: Women: 24.8(7.0)c Men: 24.4 (6.9)c

8

All with mildly elevated depressive 

ymptoms

45.0 (12.2)b 48.5 (NR) 27.3 5.8 (1.8)b 18.8 (7.1)b BDI: 10.8 (5.2)b

36 8% MDE history positive 35.3 (NR) 38.2 0.0 NR 14.1 (8.2) CES-D: 21.3 (13.9)50 0% MDD history positive 39.8 (NR) 54.5 73.2 5.9 (NR) NR BDI: 4.92 (NR)0All with current depression 41.8 (12.1)b 100.0 98.0b NR 21.6 (11.1)b

HRSD:12.8 (6.0) CES-D:29.8 (9.3) 

criteria described in AHRQ’s General Methods Guide.

ups at baseline.

 Inventory, CES-D = Center for Epidemiologic Studies-Depression Scale, FTQ = Fagerstrom Tolerance Questionnaire, FTND = Fagerstrom Test for Nicotine 

sion Rating Scale, NR = not reported, MDD = major depressive disorder; MDE = major depressive episode 
13

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Most studies were of good quality according to quality criteria described in AHRQ’s General 

Methods Guide.

42 All studies were conducted in the U.S. with English-speaking participants 

except one, which was conducted with Spanish speakers living in the U.S.51 All reports, except 

one,52 reported smoking cessation outcomes for at least 6 months from the start of the trial. 

Most studies excluded participants with current MDD; however, 19 to 78% of participants in 

these studies had a history of MDD or exceeded a screening threshold for significant depressive 

symptoms. Of the studies that recruited smokers with depression, three recruited MDD historypositive participants,53-55 two recruited participants with current depression as measured by the 

CES-D56 or the PRIME-MD,57 and one recruited participants with mildly elevated depressive 

symptoms as assessed by the BDI-II.58 For the remainder of this report, we refer to depression 

as (1) significant depressive symptoms as measured by validated assessment instrument (e.g., 

CES-D, BDI) or (2) a history of MDD.

Key Question 1. For patients with a history of a depressive 

or current significant depressive symptoms, what is the comparative 

effectiveness of different smoking cessation strategies on smoking 

abstinence rates?

Intervention Types

All but two interventions tested combination therapies consisting of some type of counseling 

and pharmacotherapy.51,53 Of the studies that included behavioral counseling, the most 

common therapy was CBT conducted in person via small group or individual therapy. Only 

one included study conducted behavioral counseling via telephone.59 Six studies included a 

behavioral mood management treatment.44,45,53,58-60 Mood management treatments ranged from 

smoking cessation–focused behavioral counseling augmented with one-time additional mood 

management counseling to intensive multisession group or individual CBT counseling. One 

study included mood management content delivered via mailed print materials.51 Of the studies 

that included antidepressant pharmacotherapies, four used bupropion,55,57,59,61 and three tested 

some other antidepressant (i.e., sertraline, fluoxetine, nortriptyline).45,54,62 Of studies that included 

antidepressants, two used NRT as a cotreatment,55,62 and two used NRT as a first-line therapy 

before offering bupropion.57,59 One study tested behavioral counseling plus a pill formulation 

of a long-acting opiate antagonist, naltrexone, as a smoking cessation aid.63 No studies using 

varenicline were identified that met our eligibility criteria. Below, we summarize the evidence 

for smoking cessation interventions for adults with depression. When able, we conducted metaanalysis to quantitatively summarize evidence of comparative effectiveness of interventions.

Comparative Effectiveness of Smoking Cessation Strategies 

NRT + Brief counseling versus placebo + brief counseling. Two studies of good quality 

compared the addition of nicotine gum to brief counseling compared to brief counseling plus 

placebo (Table 4).52,64 Kinnunen and colleagues (1996) compared the addition of 2 or 4 mg of 

nicotine gum to one-time brief counseling. Participants were advised to use the gum ad lib, with 

a target range of 9 to 15 pieces a day. In a subgroup analysis of participants with significant 

depressive symptoms as measured via the CES-D (n = 93), smokers with depression receiving 

either active gum dose were more likely to quit smoking than smokers with depression receiving 
14

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

placebo gum (29.5% versus 12.5%; p-value NR) at 3 months post–quit date. In another trial, 

Kinnunen and colleagues (2008) reported the long-term effects of adding 2 or 4 mg of nicotine 

gum to 9 sessions of brief, 5- to 10-minute counseling sessions. Among participants with 

depression (n = 196), smokers receiving nicotine gum were more likely to remain abstinent at 12 

month post–quit date than were smokers receiving placebo gum (15.1% versus 5.7%; p = 0.01). 

Table 4. Smoking Cessation Studies of NRT Plus Brief Counseling Versus Placebo Plus Brief 

Counseling 

Study, year Intervention Comparator Follow-up 

duration 

Kinnunen, 

1996

Nicotine gum + one-time brief 

individual behavioral counseling 

Placebo gum + one-time brief 

individual behavioral counseling 3 months

Kinnunen, 

2008

Nicotine gum + 9 brief in-person 

individual counseling sessions 

Placebo gum + 9 brief in-person 

individual counseling sessions 12 months

NRT + Behavioral counseling versus active control. Two studies compared the addition of 

NRT to behavioral counseling.44,57 In a two-by-two factorial design, Hall and colleagues (1996) 

compared nicotine gum to placebo gum with 10 sessions of group CBT smoking cessation 

counseling versus 10 sessions of health education (Table 5). Analyses were collapsed across 

treatment arms. Participants were given 2 mg nicotine gum or placebo gum starting at counseling 

session three and instructed to chew one piece per hour, 12 hours per day for the next 8 weeks. 

At Week 8, participants were given enough gum to taper treatment over the next 4 weeks. 

Smoking status was obtained and confirmed with biological assessments at Weeks 8, 12, 26, and 

52. For MDD history-positive participants (n = 88), 22% receiving nicotine gum were abstinent 

compared to 33% receiving placebo gum at 52 weeks (p-value NR). This study was of fair 

quality due to omission of several key quality indicators (i.e., follow-up rates, randomization and 

allocation procedures, baseline characteristics).

In a study of good quality, Hall and colleagues (2006) offered nicotine patches plus 6 weeks 

of individual staged-care CBT behavioral counseling and computerized motivational feedback 

(Table 5). All participants had a current diagnosis of depression based on the PRIME-MD. 

Counseling sessions lasted 30 minutes and took place over 8 weeks. Participants were offered 

21 mg patches for the first 6 weeks, 14 mg patches for the following 2 weeks, and then offered 

7 mg patches for an additional 2 weeks. If patients did not quit smoking with NRT or relapsed 

during treatment, patients could request bupropion. A brief contact and smoking cessation 

referral served as the control condition. Smoking status was confirmed at 3, 6, 12, and 18 months 

postrandomization by expired carbon monoxide at ≤ 10 ppm. Staged-care counseling condition 

plus NRT outperformed brief contact control over time (OR = 4.55, 95% CI 1.04 to 19.93) with 

abstinence rates of 14.11% and 9.43% at 12 months and 18.4% and 13.21% at 18 months for the 

intervention and control, respectively.
15

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Table 5. Smoking Cessation Studies of NRT Plus Behavioral Counseling Versus Active Control 

Study, year Intervention Comparator Follow-up 

duration 

Hall, 1996a

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 

12 month

Hall, 2006

Transdermal nicotine patch 

(or bupropion if failed NRT) + 

staged motivational feedback 

+ 6 sessions of individual CBT 

smoking cessation counseling 

Brief contact + list of referrals to 

smoking cessation programs and 

stop smoking guide

18 months

a Factorial design and analysis collapsed across treatment arms.

Synthesis of Evidence on NRT 

Four studies addressed comparative effectiveness of adding single-form NRT (i.e., not 

combination NRT therapy) to other cotreatments versus an active control for adults with 

depression. Most trials reported smoking cessation outcomes of 12 months or greater from point 

of randomization. Of the four studies included in this review, only one intervened with adults 

with current depression;57 results of other studies are from subgroup analyses. Cotreatments were 

heterogeneous and ranged from intensive CBT counseling to brief one-time counseling. However, 

most studies were of good quality and reported a small, positive effect for the use of NRT.

Antidepressant therapy + cotreatment versus placebo + cotreatment. Five trials reported 

results of adding antidepressants to cotreatments compared to active control condition for 

smokers with depression. Three of these studies, all of good quality and involving 255 smokers 

with depression, provided 6-month or greater outcomes data and were included in a metaanalysis.45,54,61 These studies compared antidepressants plus behavioral counseling to behavioral 

counseling plus placebo (Table 6). Two studies compared antidepressant therapy plus a 

cotreatment of behavioral counseling and NRT. These studies reported outcomes less than 6 

months postrandomization and were not included in the meta-analysis.

Table 6. Smoking Cessation Studies of Antidepressant Therapy Plus Behavioral Counseling Versus 

Placebo Plus Behavioral Counseling

Study, year Intervention Comparator Follow-up 

duration 

Covey, 2002

Sertraline + 9 individual in-person 

smoking cessation behavioral 

counseling sessions augmented 

with supportive approach to manage negative affect associated with 

quitting smoking 

Placebo + 9 individual in-person 

smoking cessation behavioral 

counseling sessions augmented 

with supportive approach 

to manage negative affect 

associated with quitting smoking

34 weeks

Hall, 1998a

Nortriptyline + 10 session of group 

CBT smoking cessation counseling 

or 10 session health education 

Placebo + 10 session of 

group CBT smoking cessation 

counseling or 10 session health 

education 

64 weeks

Hayford, 1999 Bupropion + 11 brief in-person 

individual counseling sessions 

Placebo + 11 brief in-person 

individual counseling sessions 12 months

a Factorial design and analysis collapsed across treatment arms.
16

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Participants receiving antidepressants plus behavioral counseling were not more likely to be 

abstinent compared to participants receiving behavioral counseling plus placebo at 6-month 

postrandomization (RR = 1.31, 95% CI 0.73 to 2.34, Cochran Q = 0.55, p = 0.76, I2 = 0%) 

(Figure 3). 

Figure 3. Risk of Smoking Cessation at Least 6 Months After Start of Antidepressant Therapy Plus 

Behavioral Counseling Compared With Placebo + Behavioral Counseling 

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

In a study of good quality, Evins and colleagues (2008) tested the efficacy of adding 12 weeks of 

bupropion to a cotreatment consisting of 8 weeks of transdermal NRT and 13 sessions of group 

CBT smoking cessation counseling (Table 7).55 All participants had a lifetime history of unipolar 

depressive disorder (UDD). Results were in the expected direction, favoring antidepressant use 

in combination with behavioral counseling plus NRT over behavioral counseling plus NRT alone 

(36% versus 31%; p-value NR). However, participants randomized to receive bupropion were 

no more likely to achieve smoking abstinence at end of treatment in intention-to-treat (ITT) 

analysis with dropouts considered smokers. Moreover, smoking abstinence was associated with 

depressive symptoms, regardless of antidepressant use. 

Saules and colleagues (2004) also tested the addition of an antidepressant to a cotreatment 

of NRT and behavioral counseling (Table 7).62 This study was of fair quality. Participants in 

the intervention arm received 10 weeks of transdermal NRT plus 14 weeks of either 20 or 40 

mg of fluoxetine in combination with 6 weeks of group CBT smoking cessation counseling. 

Again, results were in the expected direction and favored the addition of antidepressant therapy. 

However, among participants who were history positive for MDD (n = 30), Saules found no 

significant differences in abstinence rates when fluoxetine was added to NRT and intensive 

behavioral counseling.

Table 7. Smoking Cessation Studies of Antidepressant Therapy Plus Behavioral Counseling Plus 

NRT Versus Placebo Plus Behavioral Counseling Plus NRT

Study, year Intervention Comparator Follow-up 

duration 

Evins, 2008 Bupropion + 13 group CBT smoking 

cessation counseling + NRT patch 

Placebo + 13 group CBT smoking 

cessation counseling + NRT patch 13 weeks

Saules, 

2004

Fluoxetine + 6 group CBT smoking 

cessation counseling + NRT patch 

Placebo + 6 group CBT smoking 

cessation counseling + NRT patch 12 months
17

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Synthesis of Evidence on Antidepressants 

Five studies addressed comparative effectiveness of adding antidepressants to other cotreatments 

versus an active control (e.g., counseling + NRT + placebo) for adults with depression. For included 

studies, antidepressants were prescribed at therapeutic doses. Only two included studies recruited 

participants with histories of MDD;54,55 results of other studies are from subgroup analyses. All 

cotreatments included multisession counseling, and four studies were of good quality. However, 

there was heterogeneity in antidepressant type across included studies. Only one used bupropion, 

the only antidepressant with an FDA indication for smoking cessation. Overall, we did not find 

enough evidence to support adding antidepressants to other smoking cessation cotreatments in 

order to improve smoking cessation rates among persons with depression. 

Mood management treatment + cotreatment versus cotreatment/active control. Six trials reported 

results of adding mood management treatments to behavioral counseling (Table 8). Other 

cotreatments given to all participants include NRT,44,58-60 nortriptyline,45 or NRT plus bupropion 

or paroxetine.59 Five of these studies, involving 402 smokers with depression, provided sufficient 

data for meta-analysis.44,45,53,58,60

Table 8. Smoking Cessation Studies With a Mood Management Treatment Component

Study, year Intervention Comparator Follow-up 

duration 

Mood management treatment + behavioral counseling versus behavioral counseling

Brown, 2001 8 group sessions of depression and 

smoking cessation CBT 

8 group sessions of smoking 

cessation CBT 12 months

Mood management treatment + behavioral counseling + NRT versus behavioral counseling + NRT

Hall, 1994

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling + 

nicotine gum

5 group sessions of smoking 

cessation counseling + nicotine 

gum

52 weeks

Hall, 1996a

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling + 

nicotine gum

10 sessions of standard group 

smoking cessation health education 

+ nicotine gum

52 weeks

MacPherson, 

2010

8 group sessions of smoking cessation 

CBT that included behavioral activation 

therapy + NRT patch

8 group sessions of smoking 

cessation CBT + NRT patch 26 weeks

Mood management treatment + behavioral counseling + NRT/antidepressant versus control

Duffy, 2006

9 to 11 sessions 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

6 months

Hall, 1998a

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling + 

nortriptyline or placebo

10 session health education + 

nortriptyline or placebo 64 weeks

a Factorial design and analysis collapsed across treatment arms.
18

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

All studies included in the meta-analysis were in the expected direction, favoring the addition 

of mood management treatment to smoking cessation cotreatments (RR = 1.45, 95% CI 1.01 to 

2.07, Cochran Q = 2.16, p = 0.71, I2 = 0%). Subgroup analysis suggests smoking cessation may be 

more likely when mood management treatment was added to cotreatments that included NRT or 

antidepressants in addition to behavioral counseling (RR = 1.66, 95% CI 0.95 to 2.90, Cochran Q 

= 1.8, p = 0.62, I2 = 0%) (Figure 4). However, confidence intervals overlap, and this contrast was 

not statistically significant.
19

moking Cessation Treatments 

Evidence-based Synthesis Program

sation at Least 6 Months After Start of Mood Management Treatment Plus Cotreatment Compared to Active Control
20

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

In a study of good quality, Duffy and colleagues (2006) tested a combined smoking, depression, and 

alcohol abuse CBT counseling protocol for head-and-neck cancer survivors.59 Smokers who were 

depressed were offered NRT and bupropion or paroxetine. Content was delivered by telephone over 

the course of 9 to 11 counseling sessions. One-time behavioral counseling and referral to appropriate 

follow-up services served as the comparator condition. Among participants who were smokers and 

depressed at baseline (n = 64), 51% were nonsmokers at 6 months from end of treatment compared 

to 17% in the control arm (p-value NR). Smoking status was verified by self-report only. 

Synthesis of Evidence on Mood Management Treatment 

Six trials addressed comparative effectiveness of adding mood management treatments to other 

smoking cessation cotreatments versus an active control for adults with depression. All trials 

reported smoking cessation outcomes at 6 months or greater from point of randomization. Four 

of these trials were of good quality. Of the five trials included in the meta-analysis, only two 

studies recruited participants with either a history of MDD53 or elevated depressive symptoms.58

Results of other studies are from subgroup analyses. Overall, results indicate a small, positive 

effect for the addition of mood management treatment to smoking cessation cotreatments.

Other intervention strategies. Three additional trials tested other types of interventions. These are 

summarized below and in Table 9.

In a study of fair quality, Covey and colleagues (1999) tested behavioral counseling plus a 

long-acting opiate antagonist, naltrexone, as a smoking cessation aid.63 Participants received six 

individual brief behavioral counseling sessions. Participants in the control arm received the same 

counseling plus placebo. Smoking status was verified by blood cotinine level of < 15 ng/ml. Of 

the 36 participants with a history of MDD, results favored use of naltrexone in combination with 

counseling over counseling plus placebo (28.6% versus 9.1%; p-value NR). 

Munoz and colleagues (1997) tested the efficacy of a self-administered mood management 

intervention plus smoking cessation guide compared to a smoking cessation guide alone 

delivered through the mail for Spanish-speaking smokers.51 To be eligible for the trial, 

participants needed to indicate that they were either “completely” or “very” sure they wanted to 

quit smoking in the next 3 months. The smoking cessation guide was a 36-page booklet from the 

National Cancer Institute and contained tips on how to quit smoking. The mood management 

treatment consisted of relaxation exercises, self-monitoring booklet, and pleasant activity 

guide. An audio cassette explained how to use the materials. Among participants with a history 

of MDE, the addition of mailed mood management content improved cessation rates over the 

mailed smoking cessation guide (38.5% versus 7.4%; p = 0.01) at 6 months postrandomization. 

For smokers with current MDE, no significant differences were found (17.9% versus 8.0%; p = 

0.15). This study was of fair quality.

In another fair study, Vickers and colleagues (2009) conducted a small randomized pilot to test 

the feasibility of behavioral counseling to promote exercise as a smoking cessation intervention 

for depressed female smokers.56 Women were randomized to receive brief smoking cessation 

counseling plus 6 weeks of transdermal NRT, plus either 10 weeks of CBT to encourage exercise 

or a health education contact control condition. The intervention was feasible but did not 

significantly improve smoking cessation rates compared to the health education control (17% 

versus 23%; p = 0.75). 
21

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Table 9. Other Smoking Cessation Intervention Strategies Studies

Study, year Intervention Comparison Follow-up 

duration

Covey, 1999 Naltrexone + 6 individual in-person 

behavioral counseling sessions 

Placebo + 6 individual in-person 

behavioral counseling sessions 6 months

Munoz, 1997 Mailed smoking cessation guide + 

mood management guide 

Mailed smoking cessation guide 

+ mood management guide at 3 

months delayed

6 months

Vickers, 2009

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

24 weeks

Synthesis of Evidence on Other Intervention Strategies

We identified three other types of smoking cessation strategies, each with only one RCT. 

Covey and colleagues (1999) and Munoz both reported positive results for participants with 

depression. However, studies were of fair quality (e.g., no ITT analysis, lack of detail on study 

measures, randomization and allocation concealment procedures not well described) and with 

select populations (e.g., Spanish speakers), which limits confidence in the estimates of effects 

and applicability of results to other populations. Results of Vickers and colleagues (2009) 

demonstrated no effect for using exercise counseling as a smoking cessation intervention strategy 

for smokers with depression. 

Key Question 2. For patients with a history of a depressive 

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)?

Only two studies provided sufficient information to report differential effectiveness of smoking 

cessation intervention strategies by depression status. For both reports, study researchers conducted 

subgroup analysis only; no treatment by depression interaction effects were directly tested.

Evins and colleagues (2008) recruited 199 smokers who had a lifetime diagnosis of UDD. 

Participants were randomized to 12 weeks of bupropion versus placebo. Both groups received a 

cotreatment consisting of 8 weeks of transdermal NRT and 13 sessions of group CBT smoking 

cessation counseling.55 Among participants who were history positive for unipolar depression 

(n = 109), 39% in the bupropion arm and 32% in the control arm were abstinent at the end of 

trial (p-value NS). Among participants with current depression (n = 90), bupropion did not 

significantly improve smoking cessation rates compared to cotreatment control condition (33% 

versus 31%; p-value NS). 

Munoz and colleagues (1997) tested the efficacy of a mailed self-administered mood 

management intervention plus smoking cessation guide compared to only a smoking cessation 

guide for Spanish-speaking smokers.51 The addition of mailed mood management content 

improved cessation rates over the mailed smoking cessation guide (38.5% versus 7.4%; p = 0.01) 

at 6 months postrandomization for participants with a history of MDE. Smokers with current 

MDE did not experience significant differences (17.9% versus 8.0%; p = 0.15).
22

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Key Question 3. For patients with a history of a depressive 

or current significant depressive symptoms, are there differential effects of smoking cessation strategies by gender?

Only one included study reported a significant treatment by gender interaction among study 

participants with a history of or current depression.63 Covey and colleagues (1999) found a 

significant treatment by gender by depression interaction. Women with past histories of MDD (n

= 26) experienced higher quit rates when randomized to receive naltrexone in combination with 

six sessions of individual behavioral counseling compared to women with depression receiving 

placebo control at 6 months (22.2% versus 0%; p = 0.04). Men with past histories of MDD (n = 

10) did not experience significantly higher quit rates with naltrexone at 6 months. 

Key Question 4: For patients with a history of a depressive 

or current significant depressive symptoms, does treatment effectiveness differ by whether smoking cessation/depression treatments are 

delivered concurrently or sequentially?

No studies directly compared smoking cessation and depression treatments delivered 

concurrently versus sequentially.

Key Question 5: What is the nature and frequency of adverse effects of smoking cessation treatments in patients with a his

depressive disorder or current significant depressive symptoms?

Table 10 details reported adverse effects of the 16 included trials. Overall, 11 studies did not 

provide information on the nature and frequency of adverse effects of treatments. Of the five 

studies that reported adverse effects, three provided some level of detail about the magnitude and 

significance of adverse effects; other studies reported too few cases to conduct statistical tests. 

These three studies all evaluated the addition of antidepressants with other smoking cessation 

treatments. In two of the three studies, selected adverse effects were more common in patients 

randomized to antidepressants. 

Table 10 also summarizes change in depressive symptoms from baseline to follow-up when 

comparing intervention and control arms among participants classified as depressed at baseline. 

Seven trials did not report changes in depressive symptoms from baseline to follow-up per arm for 

participants classified as depressed at study entry. Six studies reported no significant differences. 

Of three studies that reported significant differences, only Vickers and colleagues (2009) reported 

more favorable changes in depressive symptoms associated with the control arm compared to the 

intervention arm. Kinnunen and colleagues (1996) and MacPherson and colleagues (2010) reported 

more favorable changes in depressive symptoms associated with the intervention arms. 
23

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Table 10. Adverse Effects of Included Studies

Study, year Intervention

Adverse effects reporteda

(% reported in intervention 

versus control)

Change in 

depressive 

symptomsb

Brown, 2001 8 group sessions of depression 

and smoking cessation CBT NR

No difference between 

intervention and control 

arms 

Covey, 1999

Naltrexone + 6 individual inperson behavioral counseling 

sessions

Panic attack, malaise, sleeplessness, concentration difficulty, nausea and vomiting, disoriented and 

shaky, spaciness, dizzy, abdominal 

pain, lightheadedness, shortness of 

breath

NR

Covey, 2002

Sertraline + 9 individual inperson smoking cessation 

behavioral counseling sessions 

augmented with supportive 

approach to manage negative 

affect associated with quitting 

smoking

NR

No difference between 

intervention and control 

arms

Duffy, 2006

9 to 11 sessions 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)

NR

No difference between 

intervention and control 

arms

Evins, 2008

Bupropion + 13 group sessions 

of CBT smoking cessation 

counseling + NRT patch

NR

No difference between 

intervention and control 

arms

Hall, 1994

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling 

+ nicotine gum

NR NR

Hall, 1996

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling 

+ nicotine gum

NR

No difference between 

intervention and control 

arms

Hall, 1998

5 group sessions of CBT mood 

management + 5 group sessions 

of smoking cessation counseling 

+ nortriptyline

Dry mouth (78% vs

33%)c

, lightheadedness (49% vs 

22%)c

, shaky hands (23% vs 11%)c, 

blurry vision (16% vs 6%)c

NR

Hall, 2006

Transdermal nicotine patch 

(or bupropion if failed NRT) + 

staged motivational feedback 

+ 6 sessions of individual CBT 

smoking cessation counseling

NR

No difference between 

intervention and control 

arms

Hayford, 

1999

Bupropion + 11 brief in-person 

individual counseling sessions

Headache (29% vs 31-33%) , 

insomnia (21% vs 30-35%)c

, rhinitis 

(17% vs 10 to 12%), dry mouth (5% 

vs 13%)c

, increased anxiety (11% vs 

5-7%)

NR

Kinnunen, 

1996

Nicotine gum + one-time brief 

individual behavioral counseling NR

Decrease in NRT gum 

arm and no change in 

placebo arm
24

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Study, year Intervention

Adverse effects reporteda

(% reported in intervention 

versus control)

Change in 

depressive 

symptomsb

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 jawd

NR

MacPherson, 

2010

8 group sessions of smoking 

cessation CBT that included 

behavioral activation therapy + 

NRT patch

NR

Greater decrease 

in intervention arm 

compared to control 

arm 

Munoz, 1997 Mailed smoking cessation guide 

+ mood management guide NR NR

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

NR

Vickers, 2009

10 in-person individual exercise 

counseling sessions that 

include brief smoking cessation 

counseling + NRT

NR

Decrease in health 

education arm and 

increase in exercise 

counseling arm a Adverse effects reported for all subjects in trial. 

b For participants within depressed subgroup, statistically significant change in depressive symptoms from baseline 

to follow-up.

c Statistically significant and greater proportion affected in intervention arm compared to proportion affected in 

control arm. 

d Less than 2% of low-nicotine dependent and 6% of high-nicotine dependent participants in the intervention arms 

experienced most common NRT gum adverse effects (i.e., heart palpitations, nausea, vomiting, dizziness). 

Abbreviations: CBT = cognitive behavioral therapy, NR = not reported, NRT = nicotine replacement therapy
25

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

DISCUSSION

Sum

There is a synergistic and potentially bidirectional relationship between depression and 

smoking.6,14,19,65,66 Smokers with depression are significantly less likely to quit smoking, and 

depressed individuals are more likely to be smokers.5-7 Consequently, there is a need to identify 

effective smoking cessation interventions for this disproportionately affected population. We 

conducted a systematic review of smoking cessation intervention strategies for persons with 

depression. We also sought to examine differential effects of smoking cessation treatment 

by depression status, gender, and treatment sequencing and to characterize adverse effects of 

smoking cessation treatments in patients with depression. We found insufficient evidence to 

examine moderator effects and to characterize adverse effects. However, findings suggest several 

promising smoking cessation strategies for persons with depression. We summarize and discuss 

our findings here. 

We identified three types of intervention strategies: cotreatments augmented with behavioral 

mood management treatment (six trials), cotreatments augmented with antidepressant therapy 

(five trials), and cotreatments augmented with NRT (four trials). Cotreatments generally 

consisted of some type of smoking cessation counseling (e.g., brief, behavioral), with or 

without NRT. We also identified three additional trials that used behavioral counseling to 

promote exercise plus NRT,67 mailed self-help materials,51 or long-acting opiate antagonists 

plus behavioral counseling63 as smoking cessation interventions. Overall, we found insufficient 

evidence to support exercise behavioral counseling, mailed self-help materials, or naltrexone as 

smoking cessation strategies for smokers with depression. Although both naltrexone and mailed 

self-help materials showed positive effects in single trials, further study is required to assess the 

efficacy of these strategies. Also, it is possible that we may have missed studies with unpublished 

but relevant data. 

We did not identify any studies using varenicline that met our eligibility criteria. Varenicline 

stimulates dopamine release, which reduces nicotine cravings and withdrawal symptoms, and 

blocks nicotine receptors, which may reduce the pleasurable effects of continued nicotine usage. 

Pooled results of two RCTs showed significantly higher abstinence rates at the end of 12 weeks 

of varenicline treatment compared to both placebo and bupropion.68,69 However, given the latest 

concerns about mental health instability within the veteran population,70 varenicline should be 

reserved for special cases and will require close observation.

Smokers with depression are more likely to have increased levels of negative mood both 

precessation and postcessation.15,71-73 Also, negative mood is associated with greater relapse 

rates.74,75 Mood management therapy may serve to moderate negative mood associated with 

making and maintaining a quit attempt.74 Therefore, smokers with depression may respond better 

to smoking cessation interventions augmented with mood management techniques. Our results 

support this hypothesis. Pooled results from our meta-analysis demonstrate a small, positive 

effect of adding behavioral mood management therapy to smoking cessation cotreatments. 

The number needed to treat with mood management therapy plus NRT or antidepressants is 12 

persons to get 1 additional person to quit smoking for at least 6 months. The strength of evidence 

is moderate. Only six identified trials provided enough detail to assess cessation rates among 
26

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

smokers with depression. Moreover, we found significant heterogeneity in intensity of mood 

management therapy across studies, which may influence estimates of effectiveness. 

All of the included antidepressant trials showed small, positive effects on smoking cessation, 

but a summary estimate of effect was not statistically significant. However, the strength of 

evidence for the lack of benefit for antidepressants as a smoking cessation aid for smokers with 

depression is low. Sample sizes were small and the number achieving cessation few, which limits 

precision of estimates of effects and our ability to detect statistically significant differences. 

Also, we were able to include only five trials, of which there was significant heterogeneity in 

antidepressant type. Only bupropion and nortriptyline have proven efficacy as smoking cessation 

pharmacotherapies.36,76 Meta-analysis results show little smoking cessation benefit for selective 

serotonin reuptake inhibitors such as sertraline and fluoxetine in the general population of 

smokers.36 Because results may differ by pharmacotherapy used, caution should be taken in 

applying our findings to other antidepressants that may be used to aid smokers with depression in 

quitting smoking. 

Offering NRT to smokers with depression appears to have a small, positive effect on smoking 

cessation rates among depressed smokers. Cessation rates ranged from 14 to 22% in the three 

included studies that reported outcomes of 12 months or longer.44,57,64 These cessation rates are 

higher than the 3 to 5% of smokers who successfully maintain quit attempts a year later without 

treatment aids77 and are comparable to NRT quit rates in the general population of smokers.35 Yet, 

long-term cessation rates were lower for patients with current depressive symptoms57 than for 

those who are history positive for MDD44 (14% versus 22%, respectively). Smokers with current 

depressive symptoms may have greater difficulty quitting due to more issues with nicotine 

withdrawal or worsening of depressive symptoms during a quit attempt.78 Smokers with current 

depressive symptoms may need additional support to make and maintain a quit attempt. The 

strength of evidence for NRT use among smokers with depression is moderate. Data were sparse; 

we were able to include only four trials. However, studies were of good quality and reported 

consistent results.

Ste

Our systematic review has a number of strengths that are consistent with the QUORUM 

reporting statement and the AMSTAR quality assessment of systematic reviews. These include 

a protocol-driven approach, a comprehensive literature search of multiple electronic databases, 

double data abstraction, quality assessment of the primary studies, and appropriate methods for 

combining estimates of effect. Despite these strengths, our review has several limitations. 

Foremost is that few RCTs exist that test smoking cessation interventions among smokers with 

depression. The paucity of literature has important implications for this evidence review. First, 

in order to make meaningful comparisons, we created broad intervention categories that used 

different types of counseling modes (e.g., group, individual) and pharmacotherapies. Within each 

category, there is considerable heterogeneity. For example, we identified few medication trials 

and fewer with the same type of medication. Ideally, we would have wanted to analyze trials by 

specific medications since treatment effects may vary within broad classes of medications. 

Second, few trials recruited smokers with current depression. In fact, many trials excluded 

patients with current or recent histories of depression. Therefore, many reports based 
27

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

classifications of depression on self-reported screening criteria (e.g., CES-D, BDI) for significant 

depressive symptoms. Self-report scales may be measures of general emotional distress or 

negative affect rather than specific depressive symptoms. In primary care settings, a positive 

depression screen has a positive predictive value of ≤ 50% for MDD.79 Thus, our review contains 

heterogeneity among the group of subjects included in trials classified as depressed. To address 

this heterogeneity, our protocol specified a stratified analysis by type of depression (e.g., history 

of MDD, current depressive symptoms, current MDD), but there were too few trials in any 

intervention category to follow this planned approach. Also, time since last episode, chronicity 

of depression, and other important variations in depressive disorders may be associated with 

outcomes. For example, some evidence supports that those with recurrent MDD compared to 

a single episode have worse outcomes6

 and may differentially respond to certain interventions 

that target their depressive symptoms during a quit attempt. Our review is unable to address this 

issue. Moreover, most studies included in this report excluded participants with comorbid alcohol 

or substance abuse. Results are likely not generalizable to groups with these comorbidities. 

In many instances, we examined subgroup data for this evidence review. Including studies that 

reported on subgroups of individuals with depression has limitations. By doing so, we introduce 

the possibility of false-negative studies because many of these studies were not powered to detect 

clinically important treatment effects in depressed subgroups. Meta-analysis helps to address 

this limitation, but with relatively few studies of small sample sizes, our analyses may remain 

underpowered. In addition, subgroup analyses, unless specified a priori and part of a limited 

number of subgroups evaluated, may produce false-positive or spurious results.80

Data were limited on the majority of our key questions. No studies tested differential effects 

of smoking cessation interventions by treatment sequencing among smokers with depression. 

Literature on treatment differences by gender and depression status was also sparse. Our results 

on adverse effects are limited as well. Ideally, we would have conducted a separate search for 

adverse effects in the observational literature. However, it is unlikely that much literature exists 

on these types of interventions specific to our population of interest—smokers with a history of 

depression or with current depression. Lastly, few of the trials in this evidence review included 

VA users. Although veterans have higher rates of depression and smoking compared to the 

general population,8-12 results should be generalizable to the VA population. 

C

We identified only 16 trials, encompassing 1756 smokers with depression. Just three of these 

trials actively recruited participants with elevated depressive symptoms.57,58,67 Most patients 

included in this review were history positive for depression; findings best apply to this 

population. For patients with current depression, we have little data. We were able to conduct 

meta-analyses of only two contrasts: (1) addition of any type of antidepressant and (2) treatment 

augmented by behavioral mood management counseling. Results of this systematic review 

indicate promising smoking cessation strategies for smokers with depression. 

Table 11 summarizes the strength of evidence for each of our key questions and contrasts. Our 

results support a small, positive effect for adding mood management counseling for smoking 

cessation among patients with depression. However, it is uncertain if the effects of mood 

management counseling may differ by therapy mode (individual versus group therapy). We did not 
28

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

find adequate support for adding antidepressants; we may be underpowered to detect statistically 

significant differences. Evidence suggests support for adding NRT; however, included trials were 

too varied to be analyzed quantitatively. While most trials included in this evidence review were 

of good quality and had consistent results, data were sparse. We expect that future research will 

likely have an important impact on our confidence in the estimates of effectiveness of smoking 

cessation treatments for smokers with depression. However, evidence suggests that depression does 

not need to be resolved before tobacco cessation treatment is initiated. Smokers with depression 

can successfully maintain smoking cessation. To improve the likelihood of success, health care 

providers should consider encouraging their depressed patients who smoke to seek smoking 

cessation services that include behavioral mood management treatment and NRT.

Table 11. Summary of the Strength of Evidence for Key Questions 1 to 5 

Number 

of studies 

(subjects)a

Domains pertaining to strength of evidence Magnitude of effect 

and strength of 

evidence

Risk of Bias:

Design/

Quality

Consistency Directness Precision Percentage abstinent 

from smoking at least 

6 months

postrandomization or 

relative risk ratio

Key Question 1: NRT Moderate SOE

Moderate SOE 4 (699) RCT/

Good

Consistent Direct Imprecise 14 to 22%

Key Question 1: Antidepressant therapy Low SOE

5 (484) RCT/Good Consistent Direct Imprecise 1.48 (95% CI 0.86 to 

2.54)b

Key Question 1: Mood management treatment Moderate SOE

6 (466) RCT/Good Consistent Direct Imprecise 1.45 (95% CI 1.01 to 

2.07)c

Key Question 1: Other intervention strategies Low SOE

3 (202) RCT/ Fair Inconsistent Direct Imprecise 17 to 39%

Key Question 2: Differential effects by depression status Insufficient SOE

2 (305) RCT/ Good Inconsistent Direct Imprecise 18 to 39%

Key Question 3: Differential effects by gender Insufficient SOE

1 (36) RCT/ Good Consistent Direct Imprecise 22%

Key Question 4: Differential effects by treatments delivered concurrently or 

sequentially

Insufficient SOE

0 (0) --- --- --- --- ---

Key Question 5: Adverse effects Insufficient SOE

5 (1,652) RCT/ Good Inconsistent Indirect Imprecise

a Numbers reflect participants with depression only for KQs 1 to 4 and all study participants for KQ 5.

b Magnitude of effect calculated from 3 trials included in meta-analysis (n = 255).

c Magnitude of effect calculated from 5 trials included in meta-analysis (n = 402).

Abbreviations: CI = confidence interval, RCT = randomized controlled trial, SOE = strength of evidence
29

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

FUTURE RESEARCH

While this review provides some evidence about smoking cessation strategies for patients with 

depression, more work is needed in this area. First, we found very little trial data on intervening 

with smokers who are currently depressed. Persons with depression are about twice as likely 

to be smokers than persons without depression.5

 Moreover, smokers with depression may 

experience more challenges when trying to make and maintain a quit attempt, such as greater 

negative mood symptoms from withdrawal, higher nicotine dependence, and greater likelihood 

of relapse, than smokers without depression.17,18,21,22,24,81 Secondary analysis of existing smoking 

cessation trial data could advance our understanding of smoking cessation strategies for patients 

with depression. Future studies should be designed to test smoking cessation interventions for 

this vulnerable population. Next, within the trials we identified, we found little research on 

key moderators that may influence treatment effectiveness (e.g., gender, depression status). 

Moderator analysis will facilitate subgroup identification, which may lead to better treatment 

matching.6

Evidence is growing that combination pharmacotherapy is effective for the general population 

of smokers.82 In 2009, the VA Pharmacy Benefits Management (PBM) Services released 

recommendations for the use of combination pharmacotherapy for tobacco use cessation. The 

VA PBM recommends combination NRT that involves the use of a longer acting NRT such 

as the patch in conjunction with a short-acting NRT (e.g., gum, inhaler, nasal spray) (http://

www.pbm.va.gov). Future studies should be designed to allow for direct comparisons between 

combinations of likely efficacious NRT therapies for smokers with depression. Also, it is not 

known how to combine depression and smoking pharmacotherapies. Take, for example, a patient 

with depression who is improving on sertraline but wants to stop smoking. Should the provider 

add bupropion or change from sertraline to bupropion, which may risk worsening of depression? 

Future trials should investigate combination smoking cessation and depression pharmacotherapy 

among smokers with depression. 

Behavioral counseling plus pharmacotherapy is considered the gold standard of care for effective 

smoking cessation interventions.29,37,39 Smokers with psychiatric comorbidities may benefit 

from combined behavioral counseling and pharmacotherapy with longer therapeutic approaches 

(i.e., exceeding 8 to 12 weeks) to reduce likelihood of dropout and depression relapse.41 Thus, 

future research should be designed to optimize dose, duration, and frequency of both behavioral 

counseling and pharmacotherapies. In addition, it is likely that patients with depression need 

strategies that target both depressive symptoms and smoking. Future research should seek to 

answer questions about the optimal sequencing of depression and smoking treatment content of 

smoking cessation interventions. Moreover, we were unable to tease apart the active components 

of individual therapies. Thus, important issues, such as mode of therapy (e.g., individual, 

group, telephone) and key therapeutic components (e.g., goal setting, monitoring of thoughts 

and moods, social support), cannot be answered by this systematic review. Future studies 

should be designed to disentangle active ingredients of behavioral counseling and the effects of 

delivery channels. Beyond scanning the reports included in this review, no attempt was made to 

synthesize information about adverse effects from observational studies and other data sources. 

Future research should be conducted to characterize adverse effects of treatment, including 

changes in negative affect and depressive symptoms. 
30

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

REFERENCES

1. Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United 

States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS 

Med 2009;6(4):e1000058.

2. Mokdad AH, Marks JS, Stroup DF, et al. Actual causes of death in the United States, 

2000. JAMA 2004;291(10):1238-45.

3. Cigarette smoking among adults--United States, 2006. MMWR Morb Mortal Wkly Rep 

2007;56(44):1157-61.

4. Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in 

the United States: results from the national epidemiologic survey on alcohol and related 

conditions. Arch Gen Psychiatry 2004;61(11):1107-15.

5. Lasser K, Boyd JW, Woolhandler S, et al. Smoking and mental illness: A populationbased prevalence study. JAMA 2000;284(20):2606-10.

6. Ziedonis D, Hitsman B, Beckham JC, et al. Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report. Nicotine Tob Res 2008;10(12):1691-

715.

7. Hall SM, Prochaska JJ. Treatment of smokers with co-occurring disorders: emphasis on 

integration in mental health and addiction treatment settings. Annu Rev Clin Psychol 

2009;5:409-31.

8. Hamlett-Berry K, Davison J, Kivlahan DR, et al. Evidence-based national initiatives to 

address tobacco use as a public health priority in the Veterans Health Administration. Mil 

Med 2009;174(1):29-34.

9. Black DW, Carney CP, Forman-Hoffman VL, et al. Depression in veterans of the first 

Gulf War and comparable military controls. Ann Clin Psychiatry 2004;16(2):53-61.

10. Institute of Medicine. Combating tobacco use in the military and veteran populations 

Washington, DC: The National Academies Press 2009.

11. Fiedler N, Ozakinci G, Hallman W, et al. Military deployment to the Gulf War as a risk 

factor for psychiatric illness among US troops. Br J Psychiatry 2006;188:453-9.

12. Desai MM, Rosenheck RA, Craig TJ. Case-finding for depression among medical outpatients in the Veterans Health Administration. Med Care 2006;44(2):175-81.

13. Currie SR, Hodgins DC, el-Guebaly N, et al. Influence of depression and gender on 

smoking expectancies and temptations in alcoholics in early recovery. J Subst Abuse 

2001;13(4):443-58.

14. Ischaki E, Gratziou C. Smoking and depression: Is smoking cessation effective? Ther 

Adv Respir Dis 2009;3(1):31-8.
31

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

15. Berlin I, Covey LS. Pre-cessation depressive mood predicts failure to quit smoking: the 

role of coping and personality traits. Addiction 2006;101(12):1814-21.

16. Breslau N, Johnson EO. Predicting smoking cessation and major depression in nicotinedependent smokers. Am J Public Health 2000;90(7):1122-7.

17. Kenney BA, Holahan CJ, Holahan CK, et al. Depressive symptoms, drinking problems, 

and smoking cessation in older smokers. Addict Behav 2009;34(6-7):548-53.

18. Cinciripini PM, Wetter DW, Fouladi RT, et al. The effects of depressed mood on 

smoking cessation: mediation by postcessation self-efficacy. J Consult Clin Psychol 

2003;71(2):292-301.

19. Wiesbeck GA, Kuhl HC, Yaldizli O, et al. Tobacco smoking and depression--results from 

the WHO/ISBRA study. Neuropsychobiology 2008;57(1-2):26-31.

20. Kinnunen T, Haukkala A, Korhonen T, et al. Depression and smoking across 25 years of 

the Normative Aging. Int J Psychiatry Med 2006;36(4):413-26.

21. Glassman AH, Covey LS, Stetner F, et al. Smoking cessation and the course of major 

depression: a follow-up study. Lancet 2001;357(9272):1929-32.

22. Niaura R, Britt DM, Shadel WG, et al. Symptoms of depression and survival experience 

among three samples of smokers trying to quit. Psychol Addict Behav 2001;15(1):13-7.

23. Pomerleau CS, Zucker AN, Stewart AJ. Characterizing concerns about post-cessation 

weight gain: Results from a national survey of women smokers. Nicotine Tob Res 

2001;3(1):51-60.

24. Tsoh JY, Humfleet GL, Munoz RF, et al. Development of major depression after treatment for smoking cessation. Am J Psychiatry 2000;157(3):368-74.

25. Siru R, Hulse GK, Tait RJ. Assessing motivation to quit smoking in people with mental 

illness: a review. Addiction 2009;104(5):719-33.

26. Prochaska JJ, Rossi JS, Redding CA, et al. Depressed smokers and stage of change: implications for treatment interventions. Drug Alcohol Depend 2004;76(2):143-51.

27. Hitsman B, Moss TG, Montoya ID, et al. Treatment of tobacco dependence in mental 

health and addictive disorders. Can J Psychiatry 2009;54(6):368-78.

28. Hall SM. Nicotine interventions with comorbid populations. Am J Prev Med 2007;33(6 

Suppl):S406-13.

29. Stead LF, Perera R, Lancaster T. Telephone counselling for smoking cessation. Cochrane 

Database Syst Rev 2006;3:CD002850.

30. Shiffman S, Ferguson SG. Nicotine patch therapy prior to quitting smoking: a meta-analysis. Addiction 2008;103(4):557-63.
32

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

31. Baddoura R, Wehbeh-Chidiac C. Prevalence of tobacco use among the adult Lebanese 

population. East Mediterr Health J 2001;7(4-5):819-28.

32. Stead LF, Bergson G, Lancaster T. Physician advice for smoking cessation. Cochrane 

Database Syst Rev 2008(2):CD000165.

33. Lancaster T, Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev 2005(2):CD001292.

34. Stead LF, Lancaster T. Group behaviour therapy programmes for smoking cessation. Cochrane Database Syst Rev 2005(2):CD001007.

35. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. 

Cochrane Database Syst Rev 2008(1):CD000146.

36. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007(1):CD000031.

37. Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Quick Reference Guide for Clinicians. Rockville, MD: US Department of Health 

and Human Services. Public Health Service. April 2009. Available at: http://www.ahrq.

gov/clinic/tobacco/tobaqrg.pdf. Accessed November 2010.

38. Rabius V, Pike KJ, Hunter J, et al. Effects of frequency and duration in telephone counselling for smoking cessation. Tob Control 2007;16 Suppl 1:i71-4.

39. An LC, Zhu SH, Nelson DB, et al. Benefits of telephone care over primary care for smoking cessation: a randomized trial. Arch Intern Med 2006;166(5):536-42.

40. Weinberger AH, Maciejewski PK, McKee SA, et al. Gender differences in associations 

between lifetime alcohol, depression, panic disorder, and posttraumatic stress disorder 

and tobacco withdrawal. Am J Addict 2009;18(2):140-7.

41. Gelenberg AJ, de Leon J, Evins AE, et al. Smoking cessation in patients with psychiatric 

disorders. Prim Care Companion J Clin Psychiatry 2008;10(1):52-8.

42. Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and 

Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research 

and Quality. Available at: http://www.effectivehealthcare.ahrq.gov/index.cfm/searchfor-guides-reviews-and-reports/?pageaction=displayproduct&productid=318. Accessed 

November 11, 2010.

43. West R, Hajek P, Stead L, et al. Outcome criteria in smoking cessation trials: proposal for 

a common standard. Addiction 2005;100(3):299-303.

44. Hall SM, Munoz RF, Reus VI, et al. Mood management and nicotine gum in smoking 

treatment: a therapeutic contact and placebo-controlled study. J Consult Clin Psychol 

1996;64(5):1003-9.
33

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

45. Hall SM, Reus VI, Munoz RF, et al. Nortriptyline and cognitive-behavioral therapy in the 

treatment of cigarette smoking. Arch Gen Psychiatry 1998;55(8):683-90.

46. Cochran WG. The Combination of Estimates from Different Experiments. Biometrics 

1954;10(1):101-129.

47. Fleiss JL. Analysis of data from multiclinic trials. Control Clin Trials 1986;7(4):267-75.

48. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 

2002;21(11):1539-58.

49. Higgins JP, Greenberg S. Cochrane Handbook for Systematic Reviews of Interventions 

Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available 

from www.cochrane-handbook.org.

50. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328(7454):1490.

51. Munoz RF, Marin BV, Posner SF, et al. Mood management mail intervention increases 

abstinence rates for Spanish-speaking Latino smokers. Am J Community Psychol 

1997;25(3):325-43.

52. Kinnunen T, Doherty K, Militello FS, et al. Depression and smoking cessation: characteristics of depressed smokers and effects of nicotine replacement. J Consult Clin Psychol 

1996;64(4):791-8.

53. Brown RA, Kahler CW, Niaura R, et al. Cognitive-behavioral treatment for depression in 

smoking cessation. J Consult Clin Psychol 2001;69(3):471-80.

54. Covey LS, Glassman AH, Stetner F, et al. A randomized trial of sertraline as a cessation 

aid for smokers with a history of major depression. Am J Psychiatry 2002;159(10):1731-

7.

55. Evins AE, Culhane MA, Alpert JE, et al. A controlled trial of bupropion added to nicotine 

patch and behavioral therapy for smoking cessation in adults with unipolar depressive 

disorders. J Clin Psychopharmacol 2008;28(6):660-6.

56. Vickers KS, Patten CA, Lewis BA, et al. Feasibility of an exercise counseling intervention for depressed women smokers. Nicotine Tob Res 2009;11(8):985-95.

57. Hall SM, Tsoh JY, Prochaska JJ, et al. Treatment for cigarette smoking among depressed mental health outpatients: a randomized clinical trial. Am J Public Health 

2006;96(10):1808-14.

58. MacPherson L, Tull MT, Matusiewicz AK, et al. Randomized controlled trial of behavioral activation smoking cessation treatment for smokers with elevated eepressive symptoms. J Consult Clin Psychol 2010;78(1):55-61.
34

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

59. Duffy SA, Ronis DL, Valenstein M, et al. A tailored smoking, alcohol, and depression 

intervention for head and neck cancer patients. Cancer Epidemiol Biomarkers Prev 

2006;15(11):2203-8.

60. Hall SM, Munoz RF, Reus VI. Cognitive-behavioral intervention increases abstinence 

rates for depressive-history smokers. J Consult Clin Psychol 1994;62(1):141-6.

61. Hayford KE, Patten CA, Rummans TA, et al. Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 

1999;174:173-8.

62. Saules KK, Schuh LM, Arfken CL, et al. Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral 

group therapy. Am J Addict 2004;13(5):438-46.

63. Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term 

smoking cessation. J Addict Dis 1999;18(1):31-40.

64. Kinnunen T, Korhonen T, Garvey AJ. Role of nicotine gum and pretreatment depressive 

symptoms in smoking cessation: twelve-month results of a randomized placebo controlled trial. Int J Psychiatry Med 2008;38(3):373-89.

65. Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol Psychiatry 2003;54(3):216-26.

66. John U, Meyer C, Rumpf HJ, et al. Depressive disorders are related to nicotine dependence in the population but do not necessarily hamper smoking cessation. J Clin Psychiatry 2004;65(2):169-76.

67. Vickers KS, Patten CA, Clark MM, et al. Exercise intervention for women with depressive symptoms interested in smoking cessation. Society for Research on Nicotine and 

Tobacco 11th Annual Meeting 20-23 March 2005; Prague, Czech Republic; 2005.

68. Nides M, Glover ED, Reus VI, et al. Varenicline versus bupropion SR or placebo for 

smoking cessation: a pooled analysis. Am J Health Behav 2008;32(6):664-75.

69. Nides M. Update on Pharmacologic Options for Smoking Cessation Treatment. Am J 

Med 2008;121(4 SUPPL.):S20-S31.

70. Campbell AR, Anderson KD. Mental health stability in veterans with posttraumatic stress 

disorder receiving varenicline. Am J Health Syst Pharm 2010;67(21):1832-7.

71. Haaga DA, Thorndike FP, Friedman-Wheeler DG, et al. Cognitive coping skills and depression vulnerability among cigarette smokers. Addict Behav 2004;29(6):1109-22.

72. Kahler CW, Brown RA, Ramsey SE, et al. Negative mood, depressive symptoms, and 

major depression after smoking cessation treatment in smokers with a history of major 

depressive disorder. J Abnorm Psychol 2002;111(4):670-5.
35

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

73. Kahler CW, Brown RA, Strong DR, et al. History of major depressive disorder among 

smokers in cessation treatment: associations with dysfunctional attitudes and coping. Addict Behav 2003;28(6):1033-47.

74. Carmody TP. Affect regulation, nicotine addiction, and smoking cessation. J Psychoactive 

Drugs 1992;24(2):111-22.

75. Hall SM, Munoz RF, Reus VI, et al. Nicotine, negative affect, and depression. J Consult 

Clin Psychol 1993;61(5):761-7.

76. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and 

placebo for smoking cessation. N Engl J Med 1997;337(17):1195-202.

77. Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among 

untreated smokers. Addiction 2004;99(1):29-38.

78. Haas AL, Munoz RF, Humfleet GL, et al. Influences of mood, depression history, 

and treatment modality on outcomes in smoking cessation. J Consult Clin Psychol 

2004;72(4):563-70.

79. Williams JW, Jr., Pignone M, Ramirez G, et al. Identifying depression in primary care: a 

literature synthesis of case-finding instruments. Gen Hosp Psychiatry 2002;24(4):225-37.

80. Sun X, Briel M, Walter SD, et al. Is a subgroup effect believable? Updating criteria to 

evaluate the credibility of subgroup analyses. BMJ 2010;340:c117.

81. Pomerleau CS, Brouwer RJ, Pomerleau OF. Emergence of depression during early abstinence in depressed and non-depressed women smokers. J Addict Dis 2001;20(1):73-80.

82. Shah SD, Wilken LA, Winkler SR, et al. Systematic review and meta-analysis of combination therapy for smoking cessation. J Am Pharm Assoc (2003) 2008;48(5):659-65.
36

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

APPENDIX A: SEARCH STRATEGY

PubMed: Search on March 10, 2010 (yield = 463 articles)

((“smoking cessation”[MeSH Terms] OR (“smoking”[All Fields] AND “cessation”[All Fields]) 

OR “smoking cessation”[All Fields]) OR (“Smoking/prevention and control”[Mesh:noexp] 

OR “Smoking/therapy”[Mesh:noexp])) AND (“Depression”[Mesh] OR ((“Depressive 

Disorder”[Mesh:noexp] OR “Depressive Disorder, Major”[Mesh]) OR “Dysthymic 

Disorder”[Mesh]))

Embase: Search on March 10, 2010 (yield = 489)

‘depression’/de OR ‘agitated depression’/exp OR ‘atypical depression’/exp OR ‘depressive 

psychosis’/exp OR ‘dysphoria’/exp OR ‘dysthymia’/exp OR ‘endogenous depression’/exp OR 

‘major depression’/exp OR ‘masked depression’/exp OR ‘melancholia’/exp OR ‘mixed anxiety 

and depression’/exp OR ‘mixed depression and dementia’/exp OR ‘mourning syndrome’/exp OR 

‘organic depression’/exp OR ‘reactive depression’/exp OR ‘recurrent brief depression’/exp AND 

(‘smoking cessation’/exp/mj OR ‘smoking cessation program’/exp/mj)

PsycINFO: Search on March 10, 2010 (yield = 219)

(DE “Depression (Emotion)”) or (DE “Major Depression” or DE “Affective Disorders” or 

DE “Anaclitic Depression” or DE “Dysthymic Disorder” or DE “Endogenous Depression” 

or DE “Reactive Depression” or DE “Recurrent Depression” or DE “Treatment Resistant 

Depression”) and ((“Smoking Cessation” or (DE “Drug Rehabilitation”) and (DE “Tobacco 

Smoking”))

Cochrane Library: Search on March 10, 2010 (yield = 169)

Smoking cessation and depression (limit clinical trials)
37

moking Cessation Treatments 

Evidence-based Synthesis Program

EWER COMMENTS AND RESPONSE

Response

cope, and methods for this review clearly described?

Thank you.

ew and very clearly written Thank you.

propriate outcome measures warrants more attention on p 14 or p 17 line 8. 

l 2003 report of recommendations of the abstinence outcome measures work

y for Research on Nicotine and Tobacco (Hughes J. R., Keely J. P., Niaura R. S., 

Richmond R. L., Swan G. E. Measures of abstinence in clinical trials: issues and 

Nicotine Tob Res 2003; 5: 13–25).

We have further clarified outcome measures in the methods section. Operationalization of smoking cessation was informed by those used in Cochrane reviews of smoking cessation which is based on the Russel Standard (West R, Hajek P, Stead L, Stapleton J. Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction

2005;100(3):299-303). 

biological verification of self-report (CO or cotinine) in only a couple of studies 

d as a limitation in this literature. 

All included studies use biological verification of self-report smoking cessation. 

rch strategy is among the many strengths of the review. It may be implicit in 

moking”, but it would be worth indicating on p 13 and/or in Appendix A that 

acco” are subsumed in that category. Tobacco currently only appears under 

“Tobacco” and “nicotine” are not indexed under the MESH term “smoking.” Adding these terms yields an additional 81 articles of which none met our eligibility criteria. 

Thank you.

Thank you.

e opportunity to see this work. The key questions are succinctly and clearly 

quence. Language is clear and concise. Figure 1 page 13 is helpful. In general I 

s been well conducted and well summarized. 

Thank you.

on of bias in our synthesis of the evidence?

Thank you. 

check numbers Numbers are correct.

ould be easier for the reader if you consistently describe the comparisons being 

 it would be a lot easier to grasp this if the subtitle was: “Antidepressant therapy 

 placebo +co-treatment” rather than how it is written. Same issue occurs again 

 switch “antidepressants” and “behavioral”

We agree and have made the changes requested. 

--add in risk estimates Comparisons nonsignificant and risk estimates not reported.

e report appears to be rigorously objective. Thank you.

Acknowledged
38

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

Acknowledged

Limiting the search to English Language only will introduce bias, as will 

o only the peer reviewed literature (publication bias). There may be other 

rogress. 

Non-English language articles are beyond the scope of this review. Inclusion of non–peer reviewed literature is controversial as these reports are often incomplete and can differ from final peer reviewed publication. An advantage of non-peer reviewed literature is a greater ability to detect publication bias. For this review, we thought the potential negatives of included these types of reports outweighed the potential advantages. 

ing to small positive effects of trials it is unclear whether these are statistically 

ant differences? Did they “show” effects? Or simply “suggest” effects? Or just 

be due to chance. Could the wording here be tightened so this is clearer?

We have added greater specificity to the language. 

r why hospital based interventions were excluded? If seeking to include trials 

ent depressive symptoms, then an inpatient setting might capture some of these? 

to the exclusion of relapse prevention trials may have excluded some direct or 

 efficacy of sequential treatment strategies (key question 4)

Stakeholders interested in outpatients and smoking cessation. However, we agree that including studies of relapse prevention could yield some indirect evidence but we thought that this would be too indirect for our purposes in this review. 

s on of interest to the VA that we have overlooked?

Acknowledged 

Acknowledged

y by McClure et al. appears to meet the criteria in Table 1 and is of particular 

en the focus on varenicline. If there is a reason for exclusion it would be 

and there would still appear to be value in addressing the findings as they relate 

s currently no mention of varenicline in the document. 

GE, Jack L, Catz SL, Zbikowski SM, McAfee TA, Deprey M, Richards J, Javitz 

cts and smoking outcomes among persons with and without probable lifetime 

arenicline. J Gen Intern Med. 2009 May;24(5):563-9. Epub 2009 Feb 24.

We identified and excluded McClure study because report did not provide data on rates of smoking cessation for the depressed subgroup by intervention arm. Therefore, we could not include these data in our analysis of the comparative effectiveness of smoking cessation interventions for depressed patients. 

ve reviews also seem worth citing in the background:

G, Montoya ID, George TP. Treatment of tobacco dependence in mental health 

ders. Can J Psychiatry. 2009 Jun;54(6):368-78. Review.

nterventions with comorbid populations. Am J Prev Med. 2007 Dec;33(6 

Thank you for this suggestion. We have added these to the background section.Acknowledged Acknowledged 
39

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

 based on timing of outcome reporting: figure 2 page 20. I have trouble 

ead in the report results with what is detailed about trial flow in figure 2. 

ials were excluded based on their choice of outcomes, or their choice of 

imepoint post intervention. In general terms, excluding evidence on the basis 

ecommended, if the trials otherwise meet inclusion criteria (population, design, 

he 6 articles that reported outcomes of interest, but not at 6 and 12 months, it 

ul data do exist – but not in the published reports. Some description of these 

might be informative, even if they are not subsequently able to contribute to 

alyses, or be used to inform the evidence summary. This is also true for the 14 

report the outcome of interest in their publications but otherwise met inclusion 

ulation, intervention) – perhaps the outcome data you sought does exist, and 

rom investigators. 

As we described, few (n = 3) of the studies enrolled patients with depressive symptoms. Most included studies are secondary analysis, using history of depression. The studies excluded typically report smoking cessation outcomes, but not in the subgroup of interest (those with depression) and many are small without the power to evaluate interaction effects between depression and smoking cessation interventions. Also 6- and 12-month outcomes are clinically relevant. Contacting the authors for additional data is beyond the scope of these reviews. However, we’ve raised the possibility of missing studies with unpublished but relevant outcomes.

dence, and if making suggestions for a future research agenda, then 

e additional trials might be helpful: rather than undertaking new trials, 

 better use of existing data is also important. This can take the form of 

of existing trial data, or attempting individual patient data meta-analysis

The suggestions for patient level meta-analysis or secondary analysis of existing trial data has been incorporated into possibilities for future research.

nal suggestions or comments below. If applicable, please indicate the page and line numbers from the draft report.

out the topic in general and not the report. OK
40

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

alence We added prevalence.

 include chantix? Yes, but no trials using this drug met our eligibility criteria. 

what the antidepressant trials are compared to We have clarified in text.

y: does “control condition” belong in this sentence Yes it does.

 rephrase this “...does treatment effectiveness differ by whether smoking 

n treatments are delivered concurrently or sequentially?”

We have made this change.

dding behavioral mood management counseling to _____what? We have clarified in text.

larify the sequential/concurrent text. perhaps add an example on line 16. “...

mple....”

We have clarified in text.

ht add sentence after “sequentially” that says, “It is plausible but unstudied” if 

We have added this sentence. 

ually pulled? You might rephrase this We have rephrased this sentence. 

k you should try and fit this on one page and definitely should add the setting to 

o define FTND

We have modified table and “FTND” is defined in the footnotes of Table 3. 

note it should be “approach” not “approached”. It would be nice to include a 

n this table as well as many of the others also. 

We have made this change and include summary estimates in the text, when available, for the comparisons of interest, smokers with depression by intervention arm. 

h antidepressant and behavioral to make the comparisons clearer We have changed all the title to make this clearer. 

--add in risk estimates We include risk estimates in the text, when available, for 

the comparisons of interest, smokers with depression by intervention arm.

fy what active control is We have added example of active control. 

rather than “of” We have made this change. 

ates would be helpful We include risk estimates in the text, when available, for the 

comparisons of interest, smokers with depression.

ntion rather than “interventions” We have made this change.

 the full sentence beginning in line 11-12 to the beginning of the paragraph We respectfully disagree. This sentence belongs in the 

paragraph about mood management treatments. 

“can make”???? We have clarified the language. 
41

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

entioned in the document. Perhaps the basis for the McClure et al (2009) trial dent to me for KQs 1-4, but the data on adverse effects seem highly relevant 

nd use of varenicline for patients with MH diagnoses is of high interest within 

ently revised criteria for use that emphasize psychiatric stability. 

We did not exclude trials that used varenicline. No trials using varenicline met our eligibility criteria. Therefore, it is beyond the scope of this report to discuss adverse effects for therapies not included in included trials. We, however, now briefly discuss use of varenicline for veteran with mental health issues in the discussion section.

e more explicit in distinguishing history of depression from current depression 

criteria and from current depression symptoms based on exceeding assessment 

ntified language convention in p 23 line 11-13 does not seem to be applied 

ombines current depressive symptoms with current depression diagnosis. 

e 21 – among 3 studies that recruited participants with current depression, did 

articipants meet diagnostic criteria and others use assessments in the absence of 

atements to clarify history vs. current vs. either are p 25 line 7; p 29 line 23, p 

11, p 31 line 20, p 40 line 14, Table 10 footnote b. Consider adding a footnote to 

 the distinct meanings of current depression. 

The reviewer is correct that we combined current and historypositive studies. As outlined in our research questions, we assessed the comparative effectiveness of smoking cessation strategies of patients with a history of a depressive disorder or current significant depressive symptoms. We, however, planned a priori to conduct subgroup analyses by depression status but were unable to do so due to low number of studies per comparison. We note this as a limitation of our studyWe state the method of depression assessment for the three studies that recruited participants with current depression or elevated depressive symptoms on page 23 lines 9-12. We have clarified footnote b of table 10. 

stion 2, the dimension at issue appears to be recency (i.e., history vs. current) 

s 19-20). Severity per se can vary widely among those classified as currently 

was not reflected in analyses.

For Key Question 2, we were interested in depression status at time entering trial. This could be operationalized as type or symptom severity at study entry. No studies conducted subgroup or interaction effects based on symptom severity at study entry. Therefore, we only reported on two studies that identified results based on depression type. For Key Question 2, we clarify that we were interested in depression status at study entry throughout the revised report. We intended to conduct subgroup analysis by depression status but number of studies was too few. 

al way to report trial outcomes, however to increase clinical relevance of effect 

lpful to report NNT or to advocate that this be included in future reports. For 

sider quantifying effects with NNT where possible (e.g., p 40 line 11). 

According to the Cochrane Handbook, NNT cannot be combined for a summary estimate in meta-analysis. We, therefore use RR for our analyses. We, however, have computed a NNT for our significant summary effect for the addition of mood management treatments.

cussion, most subgroup analyses warrant cautious interpretation. A recent 

e 11 would help to emphasize that point (e.g., Sun X, Briel M, Walter SD, 

group effect believable? Updating criteria to evaluate the credibility of 

BMJ. 2010 Mar 30;340 doi: 10.1136/bmj.c117). It would also be useful to 

nalyses reported in the selected studies as a priori or post hoc (e.g., p 5 line 20).

Thank you for the citation. We have added this to the report. Also studies did not state that subgroup analyses were conducted a priori and, thus, powered to detect interaction effects. We noted this as a limitation.
42

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

excluded patients with current/recent substance use or substance use disorders. 

orbidity of alcohol and other substance use disorders with smoking and 

 limitation to generalizability worth noting.

We have added this as a limitation. 

n the broader literature about the role of combination pharmacotherapy 

NRT; see Shah SD, Wilken LA, Winkler SR, Lin SJ. Review and meta

tion therapy for smoking cessation. J Am Pharm Assoc (2003). 2008 Sep

and this has resulted in guidance through VA Pharmacy Benefits (PBM-MAP 

for Use of Combination Therapy in Tobacco Use Cessation; http://www.pbm.

ww.pbm.va.gov) . This is an important area for future research on those with 

orth identifying in the Discussion and considering for the Executive Summary 

lso be cited on p 10 line 3 in the context of individual forms of NRT. P 39 line 

hat the 4 trials involved single forms of NRT and none involved combinations. P 

ast full sentence are other locations to raise this point.

We agree and stated this in our discussion of future research in and in the executive summary that combination therapies are an important area of future study. We have expanded this section and added VA PBM-specific information per the reviewer’s suggestion. We also have clarified that the NRT trials are single-form NRT trials. 

al relevance. Despite the absence of systematic analyses that address this 

seful to comment on whether/how current depression was addressed (e.g., 

-depressants or psychotherapy) other than in conditions that involved mood 

ropion, etc. , and whether any anti-depressant doses were in the therapeutic 

of depression (e.g., p 40 para 3). It seems important to comment on whether 

addresses effects of smoking cessation in the context of treatment resistant 

ated depression (e.g., p 41 para 2 or p 42 para 2). The guidance on p 44 para 

hat behavioral mood management and NRT are adequate in the context 

ated depression rather than encouraging concurrent patient engagement in 

nt care to address the depression. Note the contrast with the example on p 46 

 full sentence.

All but a few studies included in this report excluded MDD positive patients. Most patients included in this report could only be categorized as symptom positive, with no information on treatment resistance in the original papers. Therefore, we cannot comment on the effects of these smoking cessation strategies on patients with treatment resistant depression. Also we have clarified that we refer to the effects of antidepressants on smoking cessation. We were able to assess that antidepressant doses were in the therapeutic range. We have added this level of detail to the report. 

ifferential effects of mode of therapy could not be answered with available 

e of group vs. individual behavioral interventions has high relevance to 

sibility, it seems worth noting in regard to the heterogeneity of treatment 

e 8). Uncertainty about advantages of individual vs. group modality for mood 

ine 11) also would be useful to clarify.

We have added this clarification. 

ample description for Duffy; p 63 indicated 69% with current depression? Our numbers are correct. In Duffy et al., 69% of the total 

sample had depression but only 35% (n = 64) had comorbid depression and smoking at baseline. 

rt is thorough, well-written and objective. The reader gains a great deal of 

 review of studies. Several specific comments are provided below. With the 

mment about exclusion of studies relating to Figure 2 on page 20, most of these 

vely trivial, but attention to them may slightly strengthen the review.

Thank you.
43

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

, the meaning of the following sentence is a bit opaque. This sentence could 

ed or rewritten: “Yet the extent to which level of depressive symptoms affects 

fforts has not yet been synthesized.”

We agree and have deleted this sentence.

 (going onto page 11), the sentence, “Treating depression first may lead to 

herence and, consequently, better cessation rates” while having face validity, 

on, and that point should be made clear here.

We agree and have clarified that this is plausible but not yet known. 

likewise the sentence, “Smokers with psychiatric comorbidities may benefit 

avioral counseling and 3 pharmacotherapy with longer therapeutic smoking 

s (i.e., exceeding 8 to 12 4 weeks) to reduce likelihood of dropout and 

 while a reasonable supposition actually poses a hypothesis to be examined, but oes not make that point entirely clear.

The original language does not state this as a known. Our language states that these approaches may be beneficial. We then state that this needs to be studied. 

ble 1: The exclusion for relapse prevention as an outcome is not entirely 

mean that studies which randomized participants who had already quit and 

 an outcome were excluded? If so, try to make this point clearer perhaps via an 

We have added a footnote that defines relapse prevention. 

 studies were excluded because the “Main outcome not reported at desired 

 the report gives no justification for the outcome intervals selected (self-reported 

6-12 months or [secondarily] abstinence at 3-4 months.) Considering that only 

mately included in the analysis, there must be more justification for the exclusion 

s simply on the basis of outcome interval when we really do not know the 

testing abstinence that might predict long term quitting.

We have further clarified outcome measures in the methods section. Operationalization of smoking cessation was informed by those used in Cochrane reviews of smoking cessation which is based on the Russel Standard (West R, Hajek P, Stead L, Stapleton J. Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction

2005;100(3):299-303). Also, the six excluded studies reported outcomes at end of treatment. End of treatment is not likely to be a good indicator of long-term smoking cessation. 

ntidepressants” should be singular “antidepressant.” We have made this change. 

6, oral naltrexone should not be called “long acting.” The parent drug has 

of 4 hours, the active metabolite an average half-life of 12 hours. The way 

it could be confused with the long acting injectable naltrexone which has 

asting 28 days.

The original paper refers to the naltrexone used in the study as “long acting.” We have clarified that the trial used the pill form of naltrexone.

ble 6, second and third columns, second row, change “approached” to 

We have made this change. 
44

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

sider rewording the sentence, “Overall, we did not find enough evidence 

ntidepressants to other smoking cessation cotreatments for persons with 

f the studies looked at participants with prior histories of depression. If the 

depression and is trying to quit, most likely we would want her/him on an 

s effects on depression regardless of its lack of effect for smoking cessation. 

ould leave the impression that these patients should not be on antidepressants at 

Our primary outcome of interest was smoking cessation. Therefore, we were interested if adding antidepressants to smoking cessation cotreatments improves smoking cessation outcomes. It is an empirical question if persons with current depression undergoing a quit attempt receive relief from their depression with antidepressants therapy alone versus psychotherapy or combination psychotherapy and pharmacotherapy for depression. We, however, have reworded the sentence so that it is clear we are referring to antidepressant effects on smoking cessation alone. 

rite sentence, “Participants were randomized to 12 weeks of bupropion plus 

ting of 8 weeks of transdermal NRT and 13 sessions of group CBT smoking 

 or cotreatment plus placebo.” One potential suggestion is: “Participants were 

eeks of bupropion vs. placebo. Both groups received a cotreatment consisting of 8 

al NRT and 13 sessions of group CBT smoking cessation counseling.

We have changed the wording per the reviewer’s suggestion. 

tes some confusion by saying “Among participants who were history positive 

ion . . .” Whereas, earlier on line 6, the text indicates that “Evins (2008) 

ers who were history positive for unipolar depressive disorders.” The text in line 

ke all subjects were not history positive, but line 6 indicates that they were. It 

re paragraph beginning on line 6 needs reworking.

We have revised the paragraph in order to better explain that Evins (2008) recruited participants with lifetime histories of unipolar depression but then assessed cessation rates by current versus history-positive groups. 

he differences in n’s between men and women and the overall small sample size 

wing any conclusions from these data. Please either supply the quit rates for men 

 small samples sizes render the study very inconclusive. A general caveat about 

which occurs in other areas of the review appears on page 43, lines 5-11, but it 

 to include such caveats in the specific areas of the report they pertain to. This 

redundancy but may aid clarity.

We agree with the reviewer that the small number of participants limits our ability to draw any conclusion. We state this as a global limitation of many of our findings. The study did not report quit rates for men beyond end of treatment assessments. 

f possible it would be good add a column listing the interventions. The 

ted in other tables, but it is difficult for the reader to flip back and forth. The 

the adverse events is not too apparent if the reader is unsure of the intervention 

he adverse events.

We have added a column describing the interventions. 

he wording here could give the reader the impression that the interventions 

cacious, when, in fact, they have been insufficiently studied. An attempt to make 

al clause in the paragraph does not quite get there. This point should be explicitly 

We have clarified that these are understudied strategies that need further examination. 

sentence, “Smokers with depression are more likely to have increased levels of 

on and postcessation” is poorly phrased. How about, “Smokers with depression 

ave increased levels of negative mood both pre- and post-cessation.”

We have made this word change. 
45

moking Cessation Treatments 

Evidence-based Synthesis Program

Response

move word “elevated.” We removed this word.

e sentence, “Smokers with depression can make and maintain smoking 

 awkward and would benefit from rewording.

We have reworded this sentence. 

 report extremely clear and well-written. I learned a lot from the content, 

dom this important topic has been adequately studied.

Thank you.

– Which category would varenicline fit into? Also, I think it matters whether the 

g studied is bupropion or nortriptylline (both endorsed by the PHS guidelines) 

pressants. On the other hand, none of the antidepressant studies really showed 

s not necessary to separate them out.

We had insufficient number of trials to assess antidepressant effects by specific drug. We state this as a limitation. 

hange the heading for Column 2 in Table 10 to “...%reported in intervention 

e way it reads now, it appears that the control group was much more likely to 

verse effects, particularly in Hall, 1998. It was only after a few minutes that I 

ndicating that the intervention group experienced more. So, I would keep the 

ve the order in the column heading consistent with the order reported in each 

We agree and have made this change. 

e informative to have details of the disaggregated quality criteria scores for the 

rovided, I am not able to judge how trials scoring “fair” differed from those 

s would be best within the main body, but could be included in an appendix. 

s, the transparency of the review is compromised, and the leap to GRADE in 

We followed guidance in the EPC CER methods manual to report summary quality scores.

nformative and unhelpful when there are small numbers of trials. In addition, 

uded any trials not published in peer reviewed journals, making the rationale for 

nable. Thus, appendix D would be better removed.

We agree. The funnel plots were presented in the draft review for completeness but have been removed from the final review

s, displaying the outcome number (eg figure 3, 1.2.1) is confusing to the reader. 

moved from the plots.

This has been corrected.

only 1 stratum of trials, please remove the bottom summary estimate – it merely 

m summary estimate, complicates the plots and potentially confuses readers (eg 

total” – it is same as “subtotal” estimate)

This has been corrected.

helpful to order trials by the weight they contribute to the meta analysis – thus 

see which trial contributes most to the summary estimate of effect, and also 

be responsible for any heterogeneity.

We have made this change.

e and content among tables: table 9 page 34 includes a column marked “rating”, 

anation. Presumably this reflects methodological quality? Similar tables 

wing do not contain this column. 

We have deleted this column. 

 page 57 onwards are enormous and somewhat unwieldy. It is hard to see where 

nother starts. Could these be reorganised so there is clearer delineation among 

rt each new trial at the top of a page, even separate table for each trial?

We have disaggregated the evidence tables. Each table starts on a new page. 
46

moking Cessation Treatments 

Evidence-based Synthesis Program

DENCE TABLES

ess of Smoking Cessation Treatments for Patients With Depressio

al., 2001

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

CBT for smoking cessation (ST) vs ST + CBT for 

n (CBT-D)

ndomized to treatment condition according to gender, 

pressive symptoms (BDI = 9), and level of nicotine 

ce

cessation intervention: 

l interventions

 group CBT sessions in 6 wk (2 sessions clustered 

it date) colead by two therapists (clinical psychologist 

ral fellows, interns in clinical psychologist, clinical 

ists) 

onents of smoking cessation therapy included treatment 

self-monitoring, self-management, nicotine fading, 

evention, social support

ne

n intervention: 

l interventions

our group CBT sessions in 6 wk (2 sessions clustered 

it date) colead by two therapists (clinical psych post

ellows, interns in clinical psych, clinical psychologists) 

tor intervention(s)

cessation intervention: 

l interventions

our group smoking cessation only CBT sessions in 6 wk 

s clustered around quit date) colead by two therapists 

sych postdoctoral fellows, interns in clinical psych, 

ychologists) 

Inclusion criteria: - Ages 18 to 70- Smoked for at least 1 yr (10 cigarettes/day)- History of MDDExclusion criteria: - Current depression- Substance use- Current weekly psychotherapy- Use of other tobacco products- Intent to use pharmacological aid for cessation- Psychotropic therapyAge: Mean (SD): 45.1 (9.27)Gender (n [%]): Female 107 (59.8%) Race/ethnicity (n [%]): White 174 (97.2%) Baseline depression assessment: - SCID- BDI (cutoff ≥ 9)- Mean (SD) = 7.8 (6.31)Smoking characteristics: - FTND = 6.8 (1.93)- Saliva cotinine = 383.7 ng/ml (170.59)Comorbid conditions (n [%]):- History of alcohol abuse 78 (43.6%)- History of drug abuse 60 (35.8%)

Follow-up rate:6 mo = 91%12 mo = 92%Important baseline differences: NoneOutcomes of interest 1) Abstinence rate: 

6 mo 12 mo

ST 24.7 24.7CBT 24.4 32.52) Medication adherence rate: NR3) Differential effects by gender: NA4) Differential effects by depression status: NA5) Differential effects by treatment sequencing: NAReport adverse effects? No

General comments: NoneApplicability cautions: None Study-level quality assessment: GoodMeasure of smoking adequate? YesAssessment of adverse effects adequate? No

one

n intervention: None

tact time/proportion of sessions completed:

ttended out of 8 possible:

5.8 of 8 = 72.5% 

ion 5.9 of 8 = 73.7% 

t sequencing: Not done
47

moking Cessation Treatments 

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ner, 1999

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

mpared the added effectiveness of naltrexone to behav

seling (6 sessions) vs placebo treatment

l counseling + Naltrexone (n = 40) vs behavioral coun

acebo (n = 40)

cessation intervention: 

l interventions

al sessions based on the American Lung Association 

essation program (modified) conducted by trained 

nsisted of fading, target quit date and coping skills for 

nd withdrawal symptoms

eld 3 and 5 days prior to quit date, then weekly x 1 mo

e, 25 mg/day 3 to 5 days prior to quit, increased to 50 

n quit date, then increased to 75 mg/day if tolerated x 1 

n intervention: 

ddition to behavioral intervention

tor intervention(s) 

cessation intervention: 

l interventions

ssions as described above

5, 50, then 75 mg/day x 1 mo

n intervention:

bove

tact time/proportion of sessions completed: 

67.5%) subjects in both arms completed the treatment; 

 sessions attended NR

t sequencing: NA

Inclusion criteria: - Ages 18 to 65- Smoked ≥ 20 cigarettes/day- Smoked before leaving house when awakened- Made at least 1 attempt to quit in the pastExclusion criteria: - Current or history of psychiatric disorder other than MDD; not clearly specified - Current major medical illness - Current MDD, substance abuse or psychotic disorder excludedAge: Mean (SD): NR for whole sample Range 18 to 65Gender (n [%]): N (65) NR for entire sampleFemaleNaltrexone 20.4 of 30 (68%)Placebo 22.8 of 38 (60%)Race/ethnicity (n [%]): NRBaseline depression assessment: - Schedule for Affective Disorders, Lifetime version- History of depressionNaltrexone 12.5 of 30, (42%)Placebo 20 of 38 (53%)Smoking characteristics: Mean (SD):Self-report usage: - Naltrexone 34.3 (11.9) cigarettes/day- Placebo 30.3 (10.1) cigarettes/dayCotinine level:- Naltrexone: 262 (130) ng/ml- Placebo: 271 (110) ng/mlComorbid conditions (n [%]): History of major depression:- Total 37 of 68 (55%)- Naltrexone 12.6 of 30 (42%)- Placebo 20 of 38 (53%)

Follow-up rate: NRImportant baseline differences:Age p < .004Naltrexone 39.7 (8.0) yrPlacebo 33.8 (8.2) yrNaltrexone: 75% (30 of 40) patients started study, 25% dropped out prior to quit datePlacebo: 95% (38 of 40) patients started study, 5% dropped out prior to quit dateOutcomes of interest3 mo NR for entire population6 mo quit rate (n, %,OR, p)Naltrexone 30 (26.7) 1.9 nsPlacebo 36 (15.2)1) Abstinence rate:End of treatment (4 wk)Naltrexone 14 of 30 (46.7%)Placebo 10 of 38 (26.3%)OR 2.5, ns2) Medication adherence rate: NR3) Differential effects by gender:End of treatment (4 wk) ORWomen (44) 3.5Men (22) 1.46 mo quit rate:

Nal Pla OR p

Women 27.8 7.4 4.6 .07

General comments:Differential dropout prior to quit date:-Naltrexone 10 of 40 (25%)- Placebo 2 of 40 (5%)Then differential dropout during study in the opposite direction:- Naltrexone 3 of 30 (10%)- Placebo 11 of 38 (29%); reason given was that the pill was not helpfulApplicability cautions:- Mean age < 40- More than 60% femaleStudy-level quality assessment: FairComments: - Poor description of exclusion criteria- Poor description of depression measure- Unequal dropout rate prior to quit date- No ITT analysis with 25% dropout rate in one arm but only 5% in otherMeasure of smoking adequate? Yes; cotinineAssessment of adverse effects adequate?Original study questionnaire
48

moking Cessation Treatments 

Evidence-based Synthesis Program

ner, 1999

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

4) Differential effects by depression status: 4 wk OR only present or absent givenNegative (32) 0.8Positive (36) 8.46 mo quit rate: Nal Pla ORSmokers 28.6 9.1 4.0 nsWithin depressed (4 wk)Women (26) 4.4Men (10) 2.76 mo quit rate: Nal Pla OR pWomen 22.2 0.0 3.4 .045) Differential effects by treatment sequencing: NAReport adverse effects? Yes -11 naltrexone dropout- Minnesota Withdrawal Symptom Scale, 6 pt scale; side effects on original 3-point scale- List- Panic attack- Malaise- Sleeplessness- Lack of concentration- Nausea and vomiting- Disorientation- Tremors
49

moking Cessation Treatments 

Evidence-based Synthesis Program

et al., 2002

ons Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

uble-blind trial of sertraline titrated to 200 mg daily (n 

lacebo (n = 66) following 1 wk placebo run-in;

 received behavioral intervention

cessation intervention: 

l interventions

5-minute individual behavioral session that included 

moking cessation techniques (orientation to health risk, 

f cessation, coping skills for withdrawal symptoms and 

elapse) 

50 mg daily wk 1

aily wk 2aily wk 3aily wk 4-9

ication taper

n intervention: 

l interventions

cessation intervention augmented with a supportive ap

manage negative affect 

tor intervention(s)

cessation intervention: 

l interventions

ntervention

acebo

n intervention: 

l interventions

ntervention

tact time/proportion of sessions completed: 

ring 12 wk intervention, each lasting about 45 min

t sequencing: NA

Inclusion criteria: - ≥ 1 MDE that remitted ≥ 6 mo prior to study- Ages 18 to 70 - ≥ 20 cigarettes/day x ≥ 1 yr - ≥ Prior quit attempt- Decreased cigarettes by ≥ 50% on quit dateExclusion criteria: - Serious medical illness - Psychotropic medication- MDD- Alcohol or drug dependence- PTSD, panic disorder, bulimia, anorexia nervosa within past 6 mo- Other lifetime major Axis I disorders- PregnancyAge: Mean (SD): 44.5 (10.7)Gender (n [%]): Female 85 (63.4%)Race/ethnicity (n [%]): White 117 (87.3%)Baseline depression assessment: BDI-21 8.0 (7.7)CES-D 14.9 (10.8)HDRS 4.8 (4.4)Smoking characteristics: *- Yr smoking: 25.4 (10.5), 26.6 (10.8)- Cigarettes/day: 29.6 (11.5), 26.9 (9.0)- FTND: 7.1 (2.4), 6.1 (2.4)* = Placebo, interventionComorbid conditions: NR

Follow-up rate:100 of 134 (74.6%) at quit date; NR for intervention periodImportant baseline differences:FTND lower for intervention group: 6.1 (2.4) vs 7.1 (2.4)Outcomes of interest1) Abstinence rate: Post-quit day (randomization)Wk 6 (10): 19 of 66 (28.8%) placebo vs 23 of 68 (33.8%) interventionWk 30 (34): 11 of 66 (16.7%) placebo vs 8 of 68 (11.8%)When analysis was limited to the 100 subjects enrolled until quit date, there were no statistically significant differences in abstinence rates2) Medication adherence rate: NR3) Differential effects by gender: NR4) Differential effects by depression status:No interaction effect for treatment by single vs recurrent depression or baseline depression status5) Differential effects by treatment sequencing: NAReport adverse effects? Yes-Dizziness, agitation, spaciness, diarrhea- 7 placebo, 4 intervention dropped out by wk 4 due to AE

General comments:Table 2 gives AE rates but suspect scaleApplicability cautions: No concernsStudy-level quality assessment: GoodMeasure of smoking adequate? YesAssessment of adverse effects adequate? No
50

moking Cessation Treatments 

Evidence-based Synthesis Program

 al., 2006

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

 smoking, depression, alcohol abuse telephone counseling 

s enhanced usual care of brief counseling and referral to ap

ervices for substance use/abuse and/or depression (n = 91)

pants were nonterminal head and neck cancer patients

cessation intervention: 

l interventions

seline assessment and brief counseling with RN using 

ured instruments

 sessions, planned telephone counseling and workbook

was RN trained specifically for intervention

luded tobacco tactics, drinking decisions, and mood man

sing goal setting, self-monitoring, analyzing behavioral 

ts, coping, and social skills training

as needed

 replacement and/or bupropion 

n intervention: 

l interventions: None additional

ntidepressants on individual basis (bupropion, paroxetine, 

 sertraline)

tor intervention(s)

cessation intervention: 

l interventions

seline assessment and brief counseling with RN using 

ured instruments

s needed to smoking cessation, alcohol treatment, or 

alth evaluation according to insurance and ability to pay 

nd time spent standardized)

isting all services available in area (e.g., Alcoholics 

us)

fied as prescribed on individual basis

n intervention: 

l interventions

, dependent on individual referral

ne specified 

tact time/proportion of sessions completed: 

82.8%) completed all aspects of intervention 

t sequencing: NA

Inclusion criteria: - Diagnosis head and neck cancer- Comorbid smoking, depression, or problem drinking- Older than age 18- HDRS >20 or severe drinkingExclusion criteria: - Pregnant- Non-English- Terminal illness- Unstable psychiatric illnessAge: 57 (9.9) Gender (n [%]) : Male 155 (84%)Race/ethnicity (n [%]): White 166, (90%)Other 18 (10%)Baseline depression assessment:Geriatric Depression Scale-short form; score > 4 at baseline and follow-up (69% of sample depressed)Smoking characteristics: Self report; 74% of sampleComorbid conditions (n [%]):- Depression 127 (69%)- Alcohol 52 (28%)

Follow-up rate:84% at 6 mo for total population Important baseline differences: NoneOutcomes of interest- Quit rate at 6 mo for all smokers (n = 136) - Intervention, 35 of 74 (47%) - Usual care, 19 of 62 (31%)1) Abstinence rate:At 6 mo for those depressed at baseline (n = 64):Intervention 51% (18 of 35) Usual care 17% (5 of 29)2) Medication adherence rate:NR3) Differential effects by gender: NR4) Differential effects by depression status: NR5) Differential effects by treatment sequencing:Not doneReport adverse effects? No List

General comments:This study tried to treat smoking, alcohol abuse, and depression concomitantly in a group of head and neck cancer survivorsOnly 64 participants had depression and also smoked at baseline Depression was mild to moderate and excluded those with HDRS > 20Used Geriatric Depression Scale-short form > 4 to define depressedApplicability cautions: Good; 52% vets, correct age, male; all head and neck cancer patientsStudy-level quality assessment: GoodMeasure of smoking adequate? No; no biochemical validation of self-report status; self-report alone may underestimate current smokers Assessment of adverse effects adequate? No
51

moking Cessation Treatments 

Evidence-based Synthesis Program

al., 2008

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description:

on = 97

or = 102

andomization on level of nicotine dependence, failed 

treatment with NRT and/or CBT, current or past UDD 

s of group CBT + 8 wk NRT + 12 wk bupropion SR vs s of group CBT + 8 wk NRT + placebo

cessation intervention: 

l interventions

group CBT with groups up to 6 patients plus weekly vis

dy psychiatrist (session 1 treatment rationale; session 2, 

behavioral suggestions for using NRT; sessions 3 to13, behavioral strategies of maintenance of abstinence) 

T sessions did not address depression

on 12 wk (150 mg/day for 3 days and then 150 mg BID)

wk (21 mg patches for wk 2 to 6; 14 mg patches wk 7 

mg patches wk 9 and 10)

n intervention: 

tor intervention(s) 

cessation intervention: 

l interventions

bove: 13 wk of group CBT with groups up to 6 patients 

ly visit with study psychiatrist

T sessions did not address depression

wk (21 mg patches for wk 2 to 6; 14 mg patches wk 7 

mg patches wk 9 and 10)

12 wk (same schedule as bupropion)

n intervention: 

tact time/proportion of sessions completed:

0% dropped out

t sequencing: NA

Inclusion criteria:- Ages 18 to 70- Smoked > 10 cigarettes/day for more than 2 yr- Lifetime diagnosis of UDD (so current and history of depression)- History of depression or current depressionExclusion criteria: - Substance use disorder- Other psychiatric disorders- Current use of nicotine-containing products, psychotropic medications, or behavioral smoking cessation treatmentAge: Mean (SD): 43 (11) Gender (n [%]): Female 97 (49%)Race/ethnicity (n [%]): NABaseline depression assessment: HAM-D-6Smoking characteristics: - 7 day point prevalence- FNTDComorbid conditions (n [%]): Lifetime anxiety 79 (40%)

Follow-up rate:99 of 199 = 49.7%Important baseline differences:More men and fewer depression episodes in placebo armOutcomes of interest1) Abstinence rate:At 13 wk post-baseline:36% bupropion and 31% placebo using intent to treat analyses2) Medication adherence rate: NR3) Differential effects by gender: Not done4) Differential effects by depression status: Yes- Current UDD:33% (15 of 45) bupropion vs 31% (14 of 45) in placebo were abstinent - History of UDD:39% (20 of 52) bupropion vs 32% (18 of 57) in placebo were abstinent 5) Differential effects by treatment sequencing: Not doneReport adverse effects? No 

General comments: NoneApplicability cautions: Very high dropout rateStudy-level quality assessment: GoodMeasure of smoking adequate? YesAssessment of adverse effects adequate? NA
52

moking Cessation Treatments 

Evidence-based Synthesis Program

94

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

 of small group smoking cessation treatment + 5 ses

BT mood management + nicotine gum vs 5 sessions of 

up smoking cessation treatment + nicotine gum

ory negative:

= 53

0

ory positive:

= 17

29

cessation intervention: 

l interventions

essions over 8 wk (2 x for first 2 wk)

sions were “standard” smoking treatment: information 

g, gum use, quit plan 

on was delivered by 1 MD from preventive medicine 

and 1 PhD psychologist

mg gum as needed for 8 wk

9-12 wk

carry “shelf” gum for high-risk situations

n intervention: 

l interventions

 of CBT focused on mood management: 

ng of thoughts, daily activities, interpersonal contacts 

n increasing thoughts and activities related to healthy 

 to not smoking

ng pleasant activitiesng pleasant social contacts

 training

ng and modifying maladaptive thoughts

ealist life goals (manual available) 

tor intervention(s)

cessation intervention: 

l interventions

, 8 wk

up; only support; leader did not condone any specific 

ns or offered any

m as above

n intervention: None

tact time/proportion of sessions completed: NR

t sequencing: NA

Inclusion criteria: - 10+ cigarettes per day- Ages 18 to 65 Exclusion criteria: - Heart disease - Angina, vasospastic disease - Current or past peptic ulcer- Temporomandibular joint disease- Hypertension- Life-threatening illness- Alcohol or drug problems in past 6 mo- Current treatment for psychiatric problems- History of psychiatric hospitalization in past yr- Pregnant or nursing- Current MDD screened outAge: Mean (SD): 40.6 (9.2)Gender (n [%]): Men 71 (48%)Women 78 (52%)Race/ethnicity (n [%]): White 131 (88%)Baseline depression assessment: - DIS used to assess history of MDD, n = 46 (31%) history positive- BDI:History positive n = 6.39 (5.9)History negative n = 4.58 (4.6)Smoking characteristics: 24.9 (10.9) cigarettes/day26.7 (13.9) CO levelFTND tolerance scale 6.4 (1.9)Regular smoking yr 22.1 (9.5)Comorbid conditions: NR

Follow-up rate: NR; subjects with missing data were coded as smokingImportant baseline differences: NROutcomes of interest1) Abstinence rate:Wk 12 rates (from baseline)MDD history negative: Control 26 of 53 (49%)CBT 23 of 50 (46%)MDD history positive:Control 8 of 17 (47%)CBT 20 of 29 (69%)Wk 52MDD history negative: Control 13 of 53 (25%)CBT 8 of 50 (16%)MDD history positive:Control 4 of 17 (24%)CBT 10 of 29 (34%)2) Medication adherence rate: NR3) Differential effects by gender: NR4) Differential effects by depression status:See above for unadjusted rates; the diagnosis x treatment group interaction was significantAmong only those with MDD history positive, 10 of 29 (34%) vs 3 of 17 (18%) at 1 yr5) Differential effects by treatment sequencing: NAReport adverse effects? No

General comments: NoneApplicability cautions:- Current MDD or other psychiatric treatment excluded- Volunteer reactive sampleStudy-level quality assessment: Fair to poorComments:- Randomization and allocation NR- Baseline characteristics by intervention NR- Follow-up rates NR- Adherence NR- Dropout NRMeasure of smoking adequate? YesAssessment of adverse effects adequate? NR
53

moking Cessation Treatments 

Evidence-based Synthesis Program

996

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

oral treatments) x 2 (gum vs placebo) factorial design; 

by MDD history and cigarettes smoked

vioral arms 10-session group over 8 wk; quit date set 

roup session; groups 5-12 patients

 in 2 x 2 NR; n’s below collapse across 1 treatment 

ory negative:

ucation (control) n = 74

3

um n = 82m n = 75

ory positive:

= 23

21

um n = 21m n = 23

cessation intervention: 

l interventions

essions based on Hall 1994

anagement” CBT focused as described in Hall 1994; 

” smoking treatment: information on smoking, gum use, 

on was delivered by weekly supervision from PhD 

ist including review of audiotapes

mg gum at session 3 (quit date) for 8 wk

least 1 piece per hr for at least 12 hr/day during first 3 wk

wk 4-8

9-12 weeks

carry “shelf” gum for high-risk situations

 abstinent from all NRT

Inclusion criteria: - 10+ cigarettes per day- Ages 18 to 65 Exclusion criteria: - Heart disease- Ulcers- Oral thrush- Current alcohol or drug problems- Hypertension- Pregnancy- Current mental health treatment- Use of psychoactive drugs- Physician letter indicating that patient is healthy- Current MDD excludedAge: Mean (SD): 39.7 (NR)Range: 22 to 65Gender (n [%]): Women 105 (52%)Men 96 (48%)Race/ethnicity (n [%]): White 185 (92%)Baseline depression assessment: - DIS used to assess history of MDD; 22% of 201 history positive- BDI 6.71 (5.43)Smoking characteristics: - 23.8 (9.8) cigarettes/day- 27.2 (11.81) CO level- Regular smoking yr 21 (NR)Comorbid conditions: NR

Follow-up rate: NR; subjects with missing data were coded as smokingImportant baseline differences:NROutcomes of interestNo effect for treatment gum dose, MDD history, or interaction1) Abstinence rate:Wk 12 rates (from baseline)MDD history negative: Control: 26 of 74 (35%)CBT: 29 of 83 (35%)Placebo gum: 28 of 82 (34%)Active gum: 27 of 75 (36%)MDD history positive:Control: 8 of 23 (35%)CBT: 10 of 21 (48%)Placebo gum: 11 of 21 (52%)Active gum: 7 of 23 (30%)Wk 52MDD history negative: Control: 17 of 74 (23%)CBT: 23 of 83 (28%)Placebo gum: 21 of 82 (26%)Active gum: 19 of 75 (25%)MDD history positive:Control: 5 of 23 (22%)CBT: 7 of 21 (33%)Placebo gum: 7 of 21 (33%)Active gum: 5 of 23 (22%)2) Medication adherence rate: NR3) Differential effects by gender: NR4) Differential effects by depression status:See above for unadjusted rates; the diagnosis x treatment group interaction was not significant5) Differential effects by treatment sequencing: NAReport adverse effects? No

General comments:Caution: 2 x 2 factorial but data presented as if a 4-arm study, so each subject is double countedApplicability cautions:- Current MDD or other psychiatric treatment excluded- Volunteer reactive sample- Participants had to pay $75 depositStudy-level quality assessment: FairComments:- Randomization and allocation NR- Baseline characteristics by treatment group NR- Follow-up rates NR- Adherence NR- Dropout NRMeasure of smoking adequate? YesAssessment of adverse effects adequate? NR
54

moking Cessation Treatments 

Evidence-based Synthesis Program

996

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

n intervention: 

l interventions

focused on mood management:

ng of thoughts, daily activities, interpersonal contacts 

n increasing thoughts and activities related to healthy 

 to not smoking

ng pleasant activitiesng pleasant social contacts

 training

ng and modifying maladaptive thoughts

ealistic life goals (manual available) 

tor intervention(s) 

cessation intervention: 

l interventions

lth education

” smoking treatment: information on smoking, gum use, 

developed and modified each week

der provided health information and facilitated group 

 

n intervention: None

tact time/proportion of sessions completed: NR

t sequencing: NA
55

moking Cessation Treatments 

Evidence-based Synthesis Program

998

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

 health education) x 2 (nortriptyline vs placebo) 

T (n = 51)

ory positive n = 17 (33.3%)

th education (n = 48)

ory positive n = 15 (31.3%)

BT (n = 52)

ory positive n = 17 (32.7%)

ealth education (n = 48)

ory positive n = 16 (33.3)

cessation intervention: 

l interventions

ood management” CBT as described in Hall 1994

roup sessions over 8 wk

e 5-11 patients

sed on mood management skills to manage dysphoria 

ain nonsmoking and included methods to increase 

ncy of pleasant activities and decrease relapse-related 

nd techniques for increasing positive social contacts, 

g negative contacts, and improving relationships.

on delivered by 3 PhD psychologists

ind; MD visits wk 1, 2, 3

ine hydrochloride at therapeutic dose for depression; 25 

r 3 days; increased to 50 mg/day for 4 daysessed at wk 2

eased to 75 mg/day if therapeutic level not attained; 

to 100 mg/day if necessary at wk 6

se 100 mg/day; maintenance to wk 12

ng wk 13 (whenever active drug was titrated; someone 

 was titrated)

n intervention: 

l interventions

 of CBT (smoking/mood management) as above

Inclusion criteria: - 10+ cigarettes per day- Ages 21 to 65 Exclusion criteria: - Heart disease or ECG abnormalities- “Other reasons”- Current mental health treatment- Use of psychoactive drugs- Current MDD- Alcohol or other non-nicotine drug useAge: Mean (SD): Drug + CBT 41.7 (9.4)Drug + health education: 40.7 (9.6)Placebo + CBT: 40.0 (9.9)Placebo + health education: 39.4 (9.7)Gender (n [%]): Women n = 110 (55%)Men n = 89 (45%)Race/ethnicity (n [%]): White 173 (89%)Baseline depression assessment: DIS used to assess history of MDD:MDD history positive n = 65 (32.7)BDI:MDD history positive n = 7.2 (5.6)MDD history negative n = 5.5 (2.2)Smoking characteristics: Range of mean (SD) for the 4 groups:- FTND 5.4 (2.2) to 5.2 (2.2)- Yr smoking 21.7 (10.0) to 23.0 (10.7)- Daily cigarettes 21.1 (7.6) to 24.9 (12.1)Comorbid conditions: NR 

Follow-up rate: N = 47 (24%) dropped out of treatment No difference in psychological intervention or history of MDD in dropout rates but dropout higher in placebo drug (30%) vs active drug (17%) (or = 2.01; 1.05-4.06)Important baseline differences: NoneOutcomes of interest1) Abstinence rate:ITT analyses abstracted here:Wk 12 rates (from baseline)MDD history negative: Drug + CBT 56%, 19 of 34Drug + health education 61%, 20 of 33Placebo + CBT 20%,7 of 35Placebo + health education 31%, 10 of 32MDD history positive:Drug + CBT 47%, 8 of 17Drug + health education 47%, 7 of 15Placebo + CBT 41%,7 of 17Placebo + health education 19%,3 of 16 Wk 64MDD history negative:Drug + CBT 35%, 12 of 34Drug + health education 36%, 12 of 33Placebo + CBT 20%, 7 of 35Placebo + health education 22%, 7 of 32MDD history positive:Drug + CBT 24%, 4 of 17Drug + health education 20%, 3 to 15Placebo + CBT 29%, 5 of 17Placebo + health education 13%, 2 of 16

General comments:Randomization stratified by depression statusApplicability cautions:- Current MDD or other psychiatric treatment excluded- Volunteer reactive sampleStudy-level quality assessment: GoodComments:Adherence rate to behavioral treatment NRMeasure of smoking adequate? YesAssessment of adverse effects adequate? Yes
56

moking Cessation Treatments 

Evidence-based Synthesis Program

998

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

tor intervention(s)

cessation intervention: 

l interventions

lth education

der provided health information and facilitated group 

ent of quit plan; modified quit plan each week but only 

n sessions (5-11patients per group) over 8 wk. 

ncluded paper-and-pencil exercises, informational 

brief didactic presentations, homework assignments, 

ng monitoring

 above

n intervention: 

l interventions: Drug as above

tact time/proportion of sessions completed: NR

t sequencing: NA

2) Medication adherence rate:Capsules did not differ by condition or drug (active vs placebo)3) Differential effects by gender:Gender by MDD history interaction significant; MDD history positive women had poorer abstinence rates than MDD history negative (or =2.05; 1.32-3.23) but not for MDD history positive men (p = 0.20)Women:Wk 12MDD history positive 38%MDD history negative 53%Wk 64MDD history positive 20%MDD history negative 37%Men:Wk 12MDD history positive 61%MDD history negative 52%Wk 64MDD history positive 37%MDD history negative 31%4) Differential effects by depression status:See above for unadjusted rates for main effect for drug; 24% vs 12% placebo achieved continuous abstinenceThe diagnosis (i.e., MDD history) by psychological treatment by drug interaction was not significantBehavioral treatment condition by MDD history was significant
57

moking Cessation Treatments 

Evidence-based Synthesis Program

998

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

MDD history positive assigned to CBT did as well as MDD history negativeMDD history positive assigned to control were less likely to be abstinent than those assigned to CBTDrug by diagnosis was not significantThe diagnosis x treatment group interaction was not significant5) Differential effects by treatment sequencing: NAReport adverse effects?- Measured by checklist- Dry mouth 78% drug vs 33%or 7.0; 95% CI 3.73 to 13.17- Lightheaded 49% vs 22%or 2.42 1.85-6.35- Shaky hands 23% vs 11%or 2.42; 1.11-5.29- Blurry vision 16% vs 6%3.00; 1.12-7.99
58

moking Cessation Treatments 

Evidence-based Synthesis Program

l., 2006

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

act and referral control (n = 159) vs staged-care inter

 = 163)

cessation intervention: 

l interventions

ized motivational feedback based on the stages of 

odel (15 min session given at baseline, 3, 6, and 12 mo

 contemplation stage were also offered counseling

treatment program of CBT; six 30 min sessions of 

 treatments over 8 wk offered by one of two therapists 

l psychologist or PhD psychologist) 

isted of quit plan that was iteratively revised, quite date, 

about reasons for smoking, information about risks/

f quitting, information on nutrition and exercise, mood 

g, discussion of ways to increase pleasant moods and 

egative ones, use of behavioral skills to reduce relapse 

elation and social support skills. 

d 10+ cigarettes got 21 mg patch for 6 wk, 14 mg wk 

wk 9-10

NRT, could request bupropion (dose NR)

n intervention: None

tor intervention(s) 

cessation intervention: 

l interventions

act; list of referrals to smoking cessation programs and 

ing guide

ne

n intervention: None

tact time/proportion of sessions completed: NR

t sequencing: See above

Inclusion criteria: - Diagnosis of current depression based on PRIME MD- Smoked 1+ cigarettes/day in week prior to enrollment- Enrollment as a patient in one of four participating sitesExclusion criteria: - Under age 18- Non-English speaking- History of bipolar- Contraindicated to use of pharmacological treatments- Dementia or other disorders interfering with comprehension of materialsAge: Mean (SD): Control (n = 159) 42.2 (12.8) Staged care (n = 163) 41.5 (12.4)Median: NRRange: NRGender (n [%]):Male 98 (30.4%)Female 224 (69.6%)Race/ethnicity (n [%]): White 220 (68.3%)Baseline depression assessment: PRIME-MD + to be enrolledBDI-II:Control 21.4 (10.9)Staged care 20.6 (11.7)DISDSM-IV + MDD:Control 155 (97.5)Staged care 152 (93.3)Current MDD:Control 133 (83.7)Staged care 135 (82.8)Recurrent MDD:Control 89 (57.4)Staged care 79 (52.0)

Follow-up rate:3 mo:Control (n = 129; 81%)Intervention (n = 138; 85%)6 mo:Control (n = 120; 75%)Intervention (n = 125; 77%)12 mo:Control (n = 112; 70%)Intervention (n = 113; 69%)18 mo:Control (n = 110; 69%)Intervention (n = 122; 75%)Important baseline differences:Control had higher % of lifetime nicotine dependence: 74.7% vs 64.2% (not correlated with outcomes)Outcomes of interest1) Abstinence rateRates based on ITT analyses (missing = smoker)Intervention: 3 mo: 22 of 163 (13.5%)6 mo: 23 of 163 (14.11%)12 mo: 23 of 163 (14.11%)18 mo: 30 of 163 (18.4%)Control:3 mo: 15 of 159 (9.43%)6 mo: 25 of 159 (15.73%)12 mo: 15 of 159 (9.43%)18 mo: 21 of 159 (13.21%)Gee model:Main effect for treatment at 12 and 18 mo (completed only on responders) OR = 4.459 (95%) CI = 1.04 to 19.93P = 0.04412) Medication adherence rate: NR

General comments: NoneApplicability cautions:- Patients recruited from large HMO- Patients did not need to have intention to quit to enrollStudy-level quality assessment: GoodMeasure of smoking adequate? YesAssessment of adverse effects adequate? NR
59

moking Cessation Treatments 

Evidence-based Synthesis Program

l., 2006

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

Smoking characteristics: FTND:Control 4.2 (2.6)Staged care 3.8 (2.4)Number of cigarettes/day:Control 15.3 (10.3)Staged care 15.8 (10.0)CO at baseline:Control 15.2 (10.2)Staged care 15.5 (9.9)Comorbid conditions: NR

3) Differential effects by gender: NR4) Differential effects by depression status:- BDI-II not related to outcomes- Analyses conducted in only MDD (n = 307) with same pattern of results; results not shown5) Differential effects by treatment sequencing: NAReport adverse effects? No
60

moking Cessation Treatments 

Evidence-based Synthesis Program

s, et al., 1999

tions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

tion description:

upropion + behavioral intervention (n = 153) vs 150 

avioral intervention (n = 153) vs 300 mg + behavioral 

on n = 156) vs placebo (n = 153)

 cessation intervention: 

al interventions

et quit date after 1 wk of medication

lized message to stop smoking

p materials based on NCI program

-person individual counseling (10-15 min) by study as

weekly visits x 7 wk, then at 8, 12, 26, and 52 wk

ned 3 days after target quit date and at 4, 5, 7, 8, 9, 10, 

o

ion SR 50 mg BIDion SR 150 mg am + placebo pmion SR 150 mg daily x 3 days, then 150 mg BID

gs given for 7 wk

on intervention: None

ator intervention(s) 

 cessation intervention: 

al interventions

ntervention groups

BID for 7 wk, n = 153

on intervention: Nonentact time/proportion of sessions completed: 

5 (75%) completed 7 wk intervention

nt sequencing: NA

Inclusion criteria: - Age ≥ 18- Smoked ≥ 15 cigarettes/day for past yr- Motivated to stop smoking- Good general healthExclusion criteria: - History of head trauma, predisposition to seizures, anorexia nervosa, or bulimia- Current depression - Pregnancy - History of alcohol or substance abuse within past yr- Personal or family history of seizure disorder- Psychotropic medication use or NRT - Previous use of bupropion- Use of other tobacco productsAge: Mean (SD): 42 to 43 Median: NRRange: NRGender (n [%]): Female 336 (54.6%)Race/ethnicity (n [%]): White 591(96%)Baseline depression assessment: BDI-21, score range 0-63 Mean (SD) ranges from 4.1 (4.2) to 4.7 (5.0)SCID for lifetime MDD, total n = 114Smoking characteristics: Mean (SD) cigarettes/day range from 26.2 (8.5) to 27.5 (9.6)Previous serious quit attempts range from 3.5 (3.4) to 4.3 (5.4)FTND range from 7.1 (1.7) to 7.3 (1.7)Comorbid conditions (n [%]): Lifetime alcohol dependence, n = 60

Follow-up rate:396 of 615 (64%) completed 12 mo follow-upCompletion varied by bupropion group: 57% (100 mg), 65% (150 mg), 64% (300 mg), 71% (placebo), p = 0.01Important baseline differences: None between randomized groups; there were important differences between those with and without history of MDD or alcohol dependence (age, gender); however, mean changes in BDI scores did not significantly differ from zero for any groupOutcomes of interest1) Abstinence rate:3 and 12 mo rates (% of randomized)Placebo: 14.4%;12.4%100 mg: 24.2%; 19.6%150 mg: 26.1%; 22.9%300 mg: 29.5%; 23.1%p = 0.01 at 3 mo; p = 0.06 at 12 mo for all 4 groups 150 mg and 300 mg doses statistically significant compared to placebo at all time points12 mo rates for participants with history of MDDPlacebo: 2 of 28 (7%)100 mg: 4 of 28 (14%)150 mg: 5 of 19 (26%)300 mg: 4 of 20 (20%)12 mo rates for participants with history of MDD and alcohol dependencePlacebo: 1 of 3 (33%)100 mg: 2 of 7 (28.6%)150 mg: 4 of 7 (57%)300 mg: 2 of 10 (20%)

General comments:Effect of dose was dependent on diagnosis group Applicability cautions:- Mean age < 45- 96% white- 55% femaleStudy-level quality assessment: GoodComments:- Allocation concealment not specified- Differential followup rate, if dropout, assumed to be smoking and would bias against intervention- Funded by Glaxo Wellcome and included industry investigator(s)Measure of smoking adequate? YesAssessment of adverse effects adequate?Fair; measured depressive symptoms and weight change but little detail on other AE measures
61

moking Cessation Treatments 

Evidence-based Synthesis Program

s, et al., 1999

tions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

2) Medication adherence rate: NR3) Differential effects by gender: NR4) Differential effects by depression status: NR5) Differential effects by treatment sequencing: NAReport adverse effects? YesDiscontinued due to AE: Placebo: 8 (5%)100 mg: 9 (6%)150 mg: 7 (5%)300 mg: 13 (8%)Headache, insomnia*, rhinitis, dry mouth*, and anxiety were most common (* = statistically significantly more)Other:Among those continuously abstinent (n = 103), there was a dose x time interaction (p = 0.04) showing less weight gain as bupropion dose increased
62

moking Cessation Treatments 

Evidence-based Synthesis Program

lo, et al., 1996

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

g + nicotine gum 2 mg 

ing + nicotine gum 4 mg; combined gum (n = 178)ing + placebo (n = 91)

cessation intervention: 

l interventions

brief individual behavioral counseling: behavioral-cog

cedures for coping with urges, cravings and withdrawal 

; help with individual concerns about quitting, such as 

n; no further information given

 gum 2 mg ad lib; target usage of 9-15 pieces/day gum 4 mg ad lib; target usage of 9-15 pieces/day

n intervention: 

tor intervention(s)

cessation intervention: 

l interventions

ntervention group

placebo gum ad lib; target usage of 9-15 pieces/day

n intervention: None

tact time/proportion of sessions completed: NR

t sequencing: NA

Inclusion criteria: - Smoked ≥ 5 cigarettes/day- Good health- Age ≥ 20Exclusion criteria: NRAge: Mean (SD) Overall Depressed40.4 (12.6) 41.6 (12.7)Gender (n [%]):Female  Overall Depressed 145 (51%) 56 (61%)Race/ethnicity (n [%]): White  Overall Depressed 221 (82%) 74 (80%)Black  Overall Depressed 29 (11%) 11 (12%)Other  Overall Depressed 19 (7%) 8 (8%)Baseline depression assessment: CES-D, 20 items, 0-60Smoking characteristics: Mean cigarettes: 22 (10.4)Mean duration: 23.1 yr (4.0)FTND (depressed group): 5.6 (2.4)Comorbid conditions: NR

Follow-up rate: NRImportant baseline differences:NR for intervention groupsDepressed patients were more likely to be female, older, and unmarried than the nondepressedOutcomes of interest1) Abstinence rate:Depressed subgroup (n = 93) at 90 days post–quit date:- Placebo: 4 of 33 (12.5%)- Nicotine gum 2 mg and 4 mg groups: 17 of 59 (29.5%)2) Medication adherence rate:Recommended gum use: 9 to 15 pieces/dayAverage daily gum used for all groups at days 7, 30, 60, 90 was 8.1 pieces, 7.8 pieces, 6.2 pieces, 4.7 pieces, respectively3) Differential effects by gender: NR4) Differential effects by depression status: NR5) Differential effects by treatment sequencing: NAReport adverse effects? - 7 day change in CES-D scores- Placebo group (depressed): no significant change, Tukey p = 0.99- Nicotine group (depressed): lower scores, Tukey p = 0.00003

General comments: NoneApplicability cautions:- Mean age 40- > 50% female- > 80% whiteStudy-level quality assessment: Good Measure of smoking adequate?Atypical definition; less stringent than other studiesAssessment of adverse effects adequate?No; only assessed 7 day change in CES-D scores
63

moking Cessation Treatments 

Evidence-based Synthesis Program

Garvey, 2008

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

 gum, 2-4 mg (collapsed) (n = 405)

gum (n = 203)

cessation intervention: 

l interventions

 brief (5-10 min) counseling at each in-person visit (1, 

60, 90, 180, 270, and 365 days post–quit date)

Clearing the Air” on how to stop smoking was provided 

 2 or 4 mg; groups collapsed across arms as parent 

wed no difference in outcome between groups

n intervention: 

tor intervention(s) 

cessation intervention:

l interventions

 brief (5-10 mi) counseling at each in-person visit

Clearing the Air” on how to stop smoking was provided 

um

n intervention: 

tact time/proportion of sessions completed: NR

t sequencing: NA

Inclusion criteria: - Age ≥ 20- Good health- Smoke ≥ 5 cigarettes/dayExclusion criteria: - Serious medical condition- Use of psychiatric medicationsAge: Mean (SD)- NR for whole population- Depressed 38.5 (11.3)- Nondepressed 41.9 (12.0)Gender (n [%]): Female 312 (51%)Depressed female 110 (56.1%)Nondepressed female 202 (49%)Race/ethnicity (n [%]):  Depressed NondepressedWhite 154 (78.6%) 338 (82%)Black 28 (14.3%) 51(12.4%)Other 14(7.1%) 23 (5.6%)Baseline depression assessment: CES-D, range 0-60; ≥ 16 classified as depressed; 32% depressed at baselineNo information on history of depression or substance abuseSmoking characteristics: - Expired CO > 8 ppm- Number of cigarettes/day - FTNDComorbid conditions (n [%]): Depression 195 (32%) 

Follow-up rate:NR; 3 withdrew for adverse effectsImportant baseline differences:Depressed group was younger, single, and had less education; P < 0.05Outcomes of interest1) Abstinence rate:- At 3 mo:In figure, but numbers not given; would have to extrapolate numbers- At 12 mo:Nondepressed with NRT = 58 of 279 (20.1%)Nondepressed placebo = 20 of 133 (15.1%)Depressed with NRT = 12 of 126 (9.8%)Depressed with placebo = 4/70 (5.7%)2) Medication adherence rate: NR3) Differential effects by gender:NR, but effect of depression no longer significant when adjusted for differences in marital status and education4) Differential effects by depression status: NR5) Differential effects by treatment sequencing: NRReport adverse effects? Yes3 questionable reactions to NRT gum

General comments:Supplemented information using Garvey 2000Applicability cautions:- Majority female- 80% WhiteStudy-level quality assessment: GoodMeasure of smoking adequate? YesAssessment of adverse effects adequate? Yes
64

moking Cessation Treatments 

Evidence-based Synthesis Program

wicz, et al., 2010

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

tine patch + 8 wk CBT (n = 33)

icotine patch + 8 wk CBT + behavioral activation (BA) 

or overall contact time; same specially trained therapists 

ypes of sessions; taped to ensure protocol followed (20% 

cessation intervention: 

l interventions

BT (described in ST below, excluding relaxation; re

h BA)

BA (adapted from Lejuez et al. 2001)

rapy

me 8 wk

on delivered by psychology doctorate-level therapist

s specific to BA included activity monitoring (behav

kout form used for goal setting, planning, and monitor

hout); identifying enjoyable activities and quit-related, 

-maintaining, and relapse-prevention activities

mal nicotine patch for 8 wk from quit date (wk 4) with an 

e of 21 mg for 4 wk, followed by 14 mg for 2 wk, and 7 

wk

ts who smoked on average 10-12 cigarettes/day started 

4-mg patch for the first 6 wk per manufacturer’s recom

ns

n intervention: Nothing additional to BA

Inclusion criteria: - Ages 18 to 65- Smoke ≥ 10 cigarettes/day- Smoke ≥ 1 yr- BDI-II ≥ 10- No current SCID-NP diagnosisExclusion criteria: - BDI ≤ 7- SCID Axis I diagnosis- Current use of psychotropic medications- Current psychotherapy- Contraindication to nicotine patch- Use of smoking pharmacotherapy - Use of other types of tobaccoNote: Demographics were not reported by entire populationAge: Mean (SD) ST BATS  42.6 (11.5) 45.0 (12.2)Gender (n [%]): Female: ST BATS  16 (48.5%) 17 (48.6%)Race/ethnicity (n [%]): African American: ST BATS  25 (75.8%) 24 (69.7%)Baseline depression assessment: BDI, 0-62, score < or > 10: ST BATS  10.4 (7.5) 10.8 (5.2)Smoking characteristics: FTND: ST BATS  6.1 (2.1) 5.8 (1.8)Cigarettes/day: ST BATS  17.3 (8.1) 18.8 (7.1)

Follow-up rate:For abstinence obtained by biochemical verification of smoking status (others considered still smoking):Wk 1 78.6%Wk 4 83.3%Wk 16 61.9%Wk 26 64.3% Important baseline differences:None (see Table 1)Outcomes of interest1) Abstinence rate:  ST BATS ORITT:Wk 16 3/33 4/35 2.71Wk 26 0/33 5/35 ---Completers:Wk 16 6.3 15.4 2.71Wk 26 0.0 19.2 ---Rates decreased over time, but interaction between treatment and time was nsBATS >ST (wk 1-wk 26 post–quit date)abs OR 95% CI p 3.59 (1.22, 3.73) 0.02Continuous abstinence rates did not differ between treatments (p = 0.11)Depression:An interaction between treatment condition and the linear effect of time revealed that the reduction in depressive symptoms over time was greater for BATS than for ST participants (see Table 4, Figure 2)This analysis is in completers (n = 42)BDI beta SE t p -1.99 0.86 -2.31 0.02

General comments: NoneApplicability cautions:Age, gender, race, education and income all similar to veteran populationStudy-level quality assessment: GoodComments:- Repeated measures analyses using GEEs- Random allocation- Blinding not possible- Completers did not differ from ITT by demographicsMeasure of smoking adequate? Yes;only those whose smoking status was biochemically verified were considered abstinent at each time point, whereas the 26 missing participants who dropped out prior to treatment were considered as having smoked in ITT analysesAssessment of adverse effects adequate? NR
65

moking Cessation Treatments 

Evidence-based Synthesis Program

wicz, et al., 2010

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

tor intervention(s)

cessation intervention: 

l interventions

BT

rapy 

me 8 sessions

on delivered by psychology doctorate-level therapist 

s included self-monitoring, identifying effective and in

essation strategies from prior quit attempts, relaxation, 

th triggers, identifying social support for cessation, 

estyle changes (such as increasing physical activity and 

tress), relapse prevention, and homework

me as intervention

n intervention: 

l interventions: None

tact time/proportion of sessions completed: 

16 completed 7 to 8 sessions

 of 26 completed 7 to 8 sessions

t sequencing: NA

es about interventions:

red by Environmental Reward Observation Scale

Comorbid conditions: All were excluded

2) Medication adherence rate:See mean contact time3) Differential effects by gender:NR by treatment 4) Differential effects by depression status:NR by treatment5) Differential effects by treatment sequencing: NAReport adverse effects? No List
66

moking Cessation Treatments 

Evidence-based Synthesis Program

al., 1997

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

moking cessation guide and mood management guide 

e) vs smoking cessation guide and mood management 

mo (delayed)

e vs delayed:

4 MDE) vs n = 65 (52 MDE)

:

ch 2 wk chart up to 6 charts in mood management

ach assessment a 3 mo and 6 mo

aliva sample

cessation intervention: 

l interventions

A” (Guia Para Dejar de Fumar), a 36-page booklet from 

2), is an anti-smoking brochure published in Spanish 

des reasons to quit, preparing to quit, techniques to resist 

o smoke as a result of social situations, and changes in 

xercise to avoid weight gain

nagement intervention, “Tomando Control de Su Vida,” 

assette on how to use materials, 30-minute relaxation 

elf-monitoring of cigarette use booklet, pleasant activity 

 monitoring tool placed to verify receipt of materials and answer ques

ne

n intervention: 

e that we have classified the mood management module 

the smoking cessation intervention, but it could be clas

depression intervention)

tor intervention(s)

cessation intervention: 

l interventions

s delayed (3 mo) mood management; essentially a 

ntrol

ne

n intervention: None

tact time/proportion of sessions completed: NR

t sequencing: NA

Inclusion criteria: - Age 18+ - 3+ cigarettes/day- Completely or very sure they wanted to stop smoking within 3 mo- Able to read Spanish- Have access to audiotape player- Live in Bay areaExclusion criteria: NoneAge: Mean (SD): 35.3, SD = NRGender (n [%]):Women 52 (38.2%)Men 84 (61.8%)Race/ethnicity (n [%]):Latino 136 (100%)Baseline depression assessment: Modified DISCES-D for level of depressive symptomsImmediate: 21.5 (14.9)Delayed: 20.7 (12.5)Lifetime MDE n = 106Current = 53History = 53No MDE history = 30Smoking characteristics: Number of cigarettes/day 14.1 (8.2)Comorbid conditions: NR

Follow-up rate: Not clearly reportedImportant baseline differences:Delayed group had lower education and was less likely to be employedOutcomes of interest1) Abstinence rate:(by self report)Immediate (3 mo)No MDE 4 of 17Current 4 of 28MDE history 8 of 26Immediate (6 mo)No MDE 3 of 17Current 5 of 28MDE history 10 of 26Delayed (3 mo)No MDE 1 of 13Current 3 of 25MDE history 3 of 27Delayed (6 mo)No MDE 2 of 13Current 2 of 25MDE history 2 of 272) Medication adherence rate:Not clearly reportedThose returning filled out materials in immediate group vs those that did not = 45% vs 14% abstinence at 3 mo3) Differential effects by gender: NR 4) Differential effects by depression status:See above for unadjusted results5) Differential effects by treatment sequencing: NAReport adverse effects? NR

General comments:Stratified randomization (no history of MDE vs history of or current MDE)Applicability cautions;Spanish speaking onlyStudy-level quality assessment: FairComments:- Randomization and allocation concealment procedures not well described- No assessment of cotreatments (e.g., NRT)- Follow-up rates not clearly reported- Biochemical verification done, but results not reportedMeasure of smoking adequate? Yes; but not clearly reportedAssessment of adverse effects adequate? NA
67

moking Cessation Treatments 

Evidence-based Synthesis Program

l., 2004

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

dy investigated the addition of fluoxetine to standard 

to improve smoking cessation in smokers with depres

e (20 mg) + NRT + CBT (n = 48)e (40 mg) + NRT + CBT (n = 51)

 NRT + CBT (n = 51)

cessation intervention: 

l interventions

oup CBT started 2 wk prior to quit date delivered by 

erapists with treatment manual; no further information 

f either 20 mg or 40 mg of fluoxetine started 4 wk before f standard (15 mg dose) transdermal NRT started at quit 

 on 15 mg, then 2 wk 10 mg, and 2 wk 5 mg

n intervention: 

l interventions

n addition to standard CBT (fluoxetine is an antidepres

ever)

tor intervention(s)

cessation intervention: 

l interventions

ntervention group

f placebo started 4 wk before quit date 

 transdermal patch NRT as above

n intervention: 

l interventions

ntervention; nothing in addition to standard CBT

tact time/proportion of sessions completed: 

pleted active phase; no difference between groups

t sequencing: NA

Inclusion criteria: - Ages 21 to 65 - ≥ 15 cigarettes/day- Expired CO ≥ 15 ppmExclusion criteria: - Psychiatric episode in last 6 mo- Current psychiatric medication use- Pregnancy- Poor comprehension- Any clinically significant medical conditionAge: Total pop (mean) 39.78SDs NRRange: 21 to 65Placebo 20mg 40mg40.85 40.44 38.44Gender (n [%]): Female:  Placebo 20mg 40mg23 (44.7%) 31(60.8%) 27(56.9%)Race/ethnicity (n [%]): White:Placebo 20mg 40mg78.3% 74.5% 67.3%Black:Placebo 20mg 40mg21.7% 21.3% 26.5%Other:Placebo 20mg 40mg--- 4.2% 6.2%Baseline depression assessment: BDI (mean score):Placebo 20 mg 40 mg6.34 5.14 3.33Smoking characteristics: FTND (score);Placebo 20 mg 40 mg6.13 6.08 5.51Comorbid conditions (n [%]): History of MDD (%)Placebo 20 mg 40 mg17.0% 22.0% 22.0% State-Trait Anxiety (%)Placebo 20 mg 40 mg43.69% 46.29% 44.50%

Follow-up rate:Follow-up rates NR for 3, 6, 12 mo follow-upsImportant baseline differences: Higher BDI in placebo group; F(2,129) = 3.39, p = 0.037 Outcomes of interestAt 15 wk from start of study, smoking cessation = 40%1) Abstinence rate:At 15 wk:Total (n = 150)Placebo = 35.4%20 mg fluoxetine = 43.1% 40 mg fluoxetine = 43.1%History of MDD (n = 30)Placebo = 37.5%20 mg fluoxetine = 54.5%40 mg fluoxetine = 54.5%But these n’s are small ~ 102) Medication adherence: NR3) Differential effects by gender: None4) Differential effects by depression status: None5) Differential effects by treatment sequencing: NAReport adverse effects? Yes; but only that they were lower in both fluoxetine groups compared to placebo (p = 0.038) using the Minnesota Tobacco Withdrawal Symptom Checklist

General comments: Population not depressed (BDI score = 4.92 and only 20% had a history of depression), but results given by whether or not history of MDD was presentSubjects were paid $150 to complete, $25 for follow-up, and $50 at final visitApplicability cautions:College educated, mean = 79.3%Study-level quality assessment: FairComments:- No rates of treatment discontinuation by arm- Selective outcome reporting: Did not report smoking rates by arm across 3, 6, 12 mo follow-ups. - Did not report loss to follow-upMeasure of smoking adequate? Yes; cotinine Assessment of adverse effects adequate?Assessment method not given; reported that number of AEs did not differ between groups
68

moking Cessation Treatments 

Evidence-based Synthesis Program

l., 2009

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

ion description: 

dition of exercise to NRT in a depressed female popula

 smoking abstinence

on: NRT + exercise + smoking cessation behavioral 

g (n = 30)

NRT + health education + smoking cessation behavioral 

g (n = 30)

cessation intervention: 

l interventions

king cessation counseling (10 min/visit) with handouts 

Clearing the Air” brochure via same specialist as CBT 

e

mal patch NRT (21 mg/day) started on quit date (wk 4), 

through wk 10

n intervention: 

l interventions

ial cognitive theory–informed CBT exercise interven

gies (not actual exercise) to encourage patient to meet 

ACSM 1995 guidelines of moderate physical activity 

ay x 5 wk) via trained (manual and observation) patient 

specialist via ten 30 min weekly sessions

luded benefits, goal setting, reinforcement, problem 

vercoming barriers, and relapse prevention 

ctivity was self-monitored.

tor intervention(s)

cessation intervention: 

l interventions

ntervention (above); brief counseling (10 min/visit) with 

via same specialist as health education

me as intervention

n intervention: 

l interventions

e/contact control using health education via patient 

specialist; topics included sleep, nutrition, preventive 

tests

tact time/proportion of sessions completed: 

) sessions completed out of 10 sessions: 

nt Control

8.2(2.7)

Inclusion criteria: - Female- Ages 18 to 65- CES-D ≥ 16- Cigarettes ≥ 10/day for past 6 mo- Current exercise < 20 min on fewer than 3 day/wk- Ability to do exercise- Good health- Negative pregnancy test- BMI ≤ 40Exclusion criteria: - Recent MI- Substance abuse- Psychosis- Nortriptyline, bupropion- Other tobacco product use- Skin allergies or other problems with NRT patch- Suicidal ideationAge: Range: 18 to 65Mean (SD):  Treatment Control 40.9 (11.8) 41.8 (12.1)Gender (n [%]):Female 60 (100%) Race/ethnicity (n [%]): White 59 (98%) - Black 1 (2%) in exercise group- White 30 (100%) in control groupBaseline depression assessment: CES-D, 0-60, > 16 Treatment Control 29.8(9.3) 32.4(9.6)HRSD Treatment Control 12.8(6.0) 15.4(9.3)

There were no significant differences between groups on any outcome variableFollow-up rate:Wk 24 follow-up: Treatment Control 16 of 30 (53%) 15 of 30 (50%)Important baseline differences:Current psychotherapy: Treatment Control 7 (23) 11 (37)Current pharmacotherapy Treatment Control 16 (53) 19 (63)Outcomes of interest 1) Abstinences rate:Wk 24 follow-up Treatment Control 1 of 16 (6.3%) 1 of 15 (6.7%)2) Medication adherence rate:NRT: Treatment Control 36% 31%Exercise or Education: Treatment Control 49% 21%3) Differential effects by gender: NA (all female)4) Differential effects by depression status: NR5) Differential effects by treatment sequencing: NAReport adverse effects? No

General comments:Subjects were paid a nominal fee: $25 at end of treatment (wk 10) and $25 after follow-up (wk 24)Applicability cautions:- 65% college-educated- 100% overweight white femalesStudy-level quality assessment: Fair to poorComments:- Small pilot, not powered for any statistical test stronger than analysis via 2 sample, rank-sum test - In the exercise literature, not helping overweight people with the actual exercise has been shown to be of no benefit- Missing outcome data on 50% of sample by wk24Measure of smoking adequate? YesAssessment of adverse effects adequate? NR
69

moking Cessation Treatments 

Evidence-based Synthesis Program

l., 2009

ions Participant Characteristics Results and Adverse Effects

Comments/Quality Scoring

t sequencing: NA

es about interventions:

nt to note that subjects were left on their own to find 

d types of actual exercise

asured weight, weight concerns, change in mood (Posi

egative Affect Scale), fitness level (VO2 max test), and 

ctivity (physical activity recall)

Smoking characteristics: Cigarettes/day: Treatment Control 20.0 (7.8) 21.6 (7.3)FTND score ≥ 6 Treatment Control 16 (53) 20 (67)Comorbid conditions (n [%]):None medical or psychiatric; all excluded but examined weight concern: Treatment Control 5.8 (2.2%) 6.6 (2.1%)Weight, kg: Treatment Control 76.0 (15.1%) 73.6 (15.7%)

m = ante meridian (before noon), BA = behavioral activation, BATS = behavioral activation treatment for smoking, BDI-II = Beck Depression Inventory-II, BID 

ehavioral therapy, CES-D = Center for Epidemiologic Studies-Depression Scale, CI = confidence interval, CO = carbon monoxide, DIS = Diagnostic Interview 

Nicotine Dependence, GEE = generalized estimating equation, HDRS = Hamilton Depression Rating Scale, ID = identification, ITT = intention to treat, MDD 

ajor depressive episode, mg = milligram or milligrams, ml = milliliter, mo = month/months, n = number, NA = not applicable, NCI = National Cancer Institute, 

T = nicotine replacement therapy, ns = not significant, OR = odds ratio, p = probability, pm = post meridian (afternoon), POMS = Profile of Mood States, ppm = 

ntrolled trial, SCID = Structured Clinical Interview for DSM Diagnoses, SD = standard deviation, SE = standard error, ST = standard treatment, UDD = unipo

= week/weeks, yr = year/years
70

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

LIST OF INCLUDED STUDIES IN ALPHABETICAL ORDER

Brown RA, Kahler CW, Niaura R, et al. Cognitive-behavioral treatment for depression in smoking cessation. J Consult Clin Psychol 2001;69(3):471-80.

Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking 

cessation. J Addict Dis 1999;18(1):31-40.

Covey LS, Glassman AH, Stetner F, et al. A randomized trial of sertraline as a cessation aid for 

smokers with a history of major depression. Am J Psychiatry 2002;159(10):1731-7.

Duffy SA, Ronis DL, Valenstein M, et al. A tailored smoking, alcohol, and depression intervention for head and neck cancer patients. Cancer Epidemiol Biomarkers Prev 2006;15(11):2203-8.

Evins AE, Culhane MA, Alpert JE, et al. A controlled trial of bupropion added to nicotine patch 

and behavioral therapy for smoking cessation in adults with unipolar depressive disorders. J Clin 

Psychopharmacol 2008;28(6):660-6.

Hall SM, Munoz RF, Reus VI. Cognitive-behavioral intervention increases abstinence rates for 

depressive-history smokers. J Consult Clin Psychol 1994;62(1):141-6.

Hall SM, Munoz RF, Reus VI, et al. Mood management and nicotine gum in smoking treatment: 

a therapeutic contact and placebo-controlled study. J Consult Clin Psychol 1996;64(5):1003-9.

Hall SM, Reus VI, Munoz RF, et al. Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry 1998;55(8):683-90.

Hall SM, Tsoh JY, Prochaska JJ, et al. Treatment for cigarette smoking among depressed mental 

health outpatients: a randomized clinical trial. Am J Public Health 2006;96(10):1808-14.

Hayford KE, Patten CA, Rummans TA, et al. Efficacy of bupropion for smoking cessation in 

smokers with a former history of major depression or alcoholism. Br J Psychiatry 1999;174:173-8.

Kinnunen T, Doherty K, Militello FS, et al. Depression and smoking cessation: characteristics of 

depressed smokers and effects of nicotine replacement. J Consult Clin Psychol 1996;64(4):791-8.

Kinnunen T, Korhonen T, Garvey AJ. Role of nicotine gum and pretreatment depressive symptoms in smoking cessation: twelve-month results of a randomized placebo controlled trial. Int J 

Psychiatry Med 2008;38(3):373-89.

MacPherson L, Tull MT, Matusiewicz AK, et al. Randomized controlled trial of behavioral activation smoking cessation treatment for smokers with elevated depressive symptoms. J Consult 

Clin Psychol 2010;78(1):55-61.

Munoz RF, Marin BV, Posner SF, et al. Mood management mail intervention increases abstinence rates for Spanish-speaking Latino smokers. Am J Community Psychol 1997;25(3):325-43.

Saules KK, Schuh LM, Arfken CL, et al. Double-blind placebo-controlled trial of fluoxetine in 

smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy. 

Am J Addict 2004;13(5):438-46.

Vickers KS, Patten CA, Lewis BA, et al. Feasibility of an exercise counseling intervention for 

depressed women smokers. Nicotine Tob Res 2009;11(8):985-95.
71

moking Cessation Treatments 

Evidence-based Synthesis Program

LUDED STUDIES 

were reviewed in their full-text version and excluded for the reason indicated. An alphabetical reference list follows the 

dies

pulation

depressed

Main outcome not 

of interest to key 

questions

Not peer-reviewed Main outcome not 

reported at desired 

interval

Not RCT or 

secondary analysis

Analysis does 

not address key 

questions

X

X

X

X

X

X

XX

X

XXXX

X

X

X

X

X

X

XX

X

X
72

moking Cessation Treatments 

Evidence-based Synthesis Program

pulation

depressed

Main outcome not 

of interest to key 

questions

Not peer-reviewed Main outcome not 

reported at desired 

interval

Not RCT or 

secondary analysis

Analysis does 

not address key 

questions

XX

X

X

X

X

X

X

X

X

XXXXX XX

X

X

X X

X

X

XXX

X

X

X

X

X
73

moking Cessation Treatments 

Evidence-based Synthesis Program

pulation

depressed

Main outcome not 

of interest to key 

questions

Not peer-reviewed Main outcome not 

reported at desired 

interval

Not RCT or 

secondary analysis

Analysis does 

not address key 

questions

X

XX

X

X

X

XX

X

X

XXXXXX

X

XX

X

XX
74

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

LIST OF EXCLUDED STUDIES 

Acton GS, Kunz JD, Wilson M, et al. The construct of internalization: conceptualization, measurement, and prediction of smoking treatment outcome. Psychol Med 2005;35(3):395-408.

Alderton W, Karran E, Ward S. Current and Future Perspectives in Psychiatric Drug Discovery. 

Drug News Perspect 2009;22(6):360-4.

Barnett PG, Wong W, Hall S. The cost-effectiveness of a smoking cessation program for outpatients in treatment for depression. Addiction 2008;103(5):834-40.

Bercaw EL. A behavioral activation approach to smoking cessation for depressed smokers at 

veterans affairs medical centers. ProQuest Information & Learning; 2008.

Berlin I, Covey LS. Pre-cessation depressive mood predicts failure to quit smoking: the role of 

coping and personality traits. Addiction 2006;101(12):1814-21.

Blondal T, Gudmundsson LJ, Tomasson K, et al. The effects of fluoxetine combined with 

nicotine inhalers in smoking cessation--a randomized trial. Addiction (Abingdon, England) 

1999(7):1007-15.

Brown RA, Niaura R, Lloyd-Richardson EE, et al. Bupropion and cognitive-behavioral treatment 

for depression in smoking cessation. Nicotine Tob Res 2007;9(7):721-30.

Buchanan LM, El-Banna M, White A, et al. An exploratory study of multicomponent treatment 

intervention for tobacco dependency. Journal of nursing scholarship : an official publication of 

Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau 2004(4):324-30.

Capone D-AL. An emotion-focused problem-solving smoking cessation intervention for depression-prone college students. ProQuest Information & Learning; 2003.

Carmody TP, Duncan C, Simon JA, et al. Hypnosis for smoking cessation: A randomized trial. 

Nicotine Tob Res 2008;10(5):811-818.

Carton S, Le Houezec J, Lagrue G, et al. Early emotional disturbances during nicotine patch 

therapy in subjects with and without a history of depression. J Affect Disord 2002;72(2):195-9.

Catley D, Ahluwalia JS, Resnicow K, et al. Depressive symptoms and smoking cessation among 

inner-city African Americans using the nicotine patch. Nicotine Tob Res 2003;5(1):61-8.

Catley D, Harris KJ, Okuyemi KS, et al. The influence of depressive symptoms on smoking cessation among African Americans in a randomized trial of bupropion. Nicotine Tob Res 

2005;7(6):859-70.

Collins BN, Niaura R, Wileyto EP, et al. Effect of bupropion on depression symptoms in highly 

dependent smokers. Society for Research on Nicotine and Tobacco 9th Annual Meeting February 

19-22 New Orleans, LA 2003:98.

Cornelius JR, Salloum Ihsan M, Ehler JG, et al. Double-blind fluoxetine in depressed alcoholic 

smokers. Psychopharmacol Bull 1997;33(1):165-170.
75

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Covey LS, Botello-Harbaum M, Glassman AH, et al. Smokers’ response to combination bupropion, nicotine patch, and counseling treatment by race/ethnicity. Ethn Dis 2008(1):59-64.

Covey LS, Glassman AH, Stetner F. Depression and depressive symptoms in smoking cessation. 

Compr Psychiatry 1990;31(4):350-4.

Cox LS, Patten CA, Niaura RS, et al. Efficacy of bupropion for relapse prevention in smokers 

with and without a past history of major depression. J Gen Intern Med 2004;19(8):828-34.

Csonka A, Jonas Z. The combination of targeted cognitive-behavioural psychotherapy and pharmacotherapy for patients suffering from depression in smoking cessation. International Journal 

of Neuropsychopharmacology 2008(Suppl. 1):92.

Dalack GW, Glassman AH, Rivelli S, et al. Mood, major depression, and fluoxetine response in 

cigarette smokers. Am J Psychiatry 1995;152(3):398-403.

Frederick SL, Humfleet GL, Hall SM, et al. Sex differences in the relation of mood to weight 

gain after quitting smoking. Experimental and Clinical Psychopharmacology 1996;4(2):178-185.

Friend KB, Pagano ME. Timevarying predictors of smoking cessation among individuals in 

treatment for alcohol abuse and dependence: findings from Project MATCH. Alcohol Alcohol 

2007;42(3):234-40.

Gilbert DG, Crauthers DM, Mooney DK, et al. Effects of monetary contingencies on smoking 

relapse: influences of trait depression, personality, and habitual nicotine intake. Exp Clin Psychopharmacol 1999;7(2):174-81.

Ginsberg D, Hall SM, Reus VI, et al. Mood and depression diagnosis in smoking cessation. Experimental and Clinical Psychopharmacology 1995;3(4):389-395.

Ginsberg JP, Klesges RC, Johnson KC, et al. The relationship between a history of depression 

and adherence to a multicomponent smoking-cessation program. Addict Behav 1997;22(6):783-

7.

Glassman AH, Covey LS, Dalack GW, et al. Smoking cessation, clonidine, and vulnerability to 

nicotine among dependent smokers. Clin Pharmacol Ther 1993;54(6):670-9.

Glassman AH, Covey LS, Stetner F, et al. Smoking cessation and the course of major depression: 

a follow-up study. Lancet 2001;357(9272):1929-32.

Glassman AH, Stetner F, Walsh BT, et al. Heavy smokers, smoking cessation, and clonidine. 

Results of a double-blind, randomized trial. JAMA 1988;259(19):2863-6.

Haas AL, Munoz RF, Humfleet GL, et al. Influences of mood, depression history, and treatment 

modality on outcomes in smoking cessation. J Consult Clin Psychol 2004;72(4):563-70.

Hayford KE, Patten CA, Rummans TA, et al. Effectiveness of Bupropion for Smoking Cessation 

for Smokers with a History of Major Depression CONFERENCE ABSTRACT. 150th Annual 

Meeting of the American Psychiatric Association. San Diego, California, USA. 17-22 May, 1997. 

1997.
76

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Helgason AR, Tomson T, Lund KE, et al. Factors related to abstinence in a telephone helpline for 

smoking cessation. European Journal of Public Health 2004;14(3):306-310.

Hernandez-Reif M, Field T, Hart S. Smoking cravings are reduced by self-massage. Prev Med 

1999;28(1):28-32.

Hill KP, Chang G. Cognitive behavioral therapy and nicotine replacement for smoking cessation in psychiatric outpatients with major depression. Addictive Disorders and their Treatment 

2007;6(2):67-72.

Hitsman B, Pingitore R, Spring B, et al. Antidepressant pharmacotherapy helps some cigarette 

smokers more than others. J Consult Clin Psychol 1999;67(4):547-54.

Jarvik ME, Caskey NH, Wirshing WC, et al. Bromocriptine reduces cigarette smoking. Addiction 

(Abingdon, England) 2000(8):1173-83.

Keuthen NJ, Niaura RS, Borrelli B, et al. Comorbidity, smoking behavior and treatment outcome. Psychother Psychosom 2000;69(5):244-50.

Killen JD, Fortmann SP, Davis L, et al. Do heavy smokers benefit from higher dose nicotine 

patch therapy? Experimental and Clinical Psychopharmacology 1999;7(3):226-233.

Killen JD, Fortmann SP, Schatzberg AF, et al. Extended cognitive behavior therapy for cigarette 

smoking cessation. Addiction (Abingdon, England) 2008(8):1381-90.

Lerman C, Kaufmann V, Rukstalis M, et al. Individualizing nicotine replacement therapy for the 

treatment of tobacco dependence: a randomized trial. Ann Intern Med; 2004:426-33. (A)

Lerman C, Niaura R, Collins BN, et al. Effect of bupropion on depression symptoms in a smoking cessation clinical trial. Psychol Addict Behav 2004;18(4):362-6. (B)

Leventhal AM, Ramsey SE, Brown RA, et al. Dimensions of depressive symptoms and smoking 

cessation. Nicotine Tob Res 2008;10(3):507-17.

Levine MD. The effect of depression history on smoking cessation in weight-concerned women. 

ProQuest Information & Learning; 2000.

McCarthy DE, Piasecki TM, Lawrence DL, et al. A randomized controlled clinical trial of bupropion SR and individual smoking cessation counseling. Nicotine Tob Res 2008;10(4):717-729.

McClure JB, Swan GE, Jack L, et al. Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline. J Gen Intern Med 

2009;24(5):563-9.

McFall M, Saxon AJ, Thompson CE, et al. Improving the rates of quitting smoking for veterans 

with posttraumatic stress disorder. The American Journal of Psychiatry 2005(7):1311-9.

McHugh F, Lindsay GM, Hanlon P, et al. Nurse led shared care for patients on the waiting list 

for coronary artery bypass surgery: a randomised controlled trial. Heart (British Cardiac Society) 

2001(3):317-23.
77

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Mermelstein R, Hedeker D, Wong SC. Extended telephone counseling for smoking cessation: 

Does content matter? J Consult Clin Psychol 2003;71(3):565-574.

Munoz RF, Lenert LL, Delucchi K, et al. Toward evidence-based Internet interventions: A Spanish/English Web site for international smoking cessation trials. Nicotine Tob Res 2006;8(1):77-

87.

Oncken C, Cooney J, Feinn R, et al. Transdermal nicotine for smoking cessation in postmenopausal women. Addict Behav 2007;32(2):296-309.

Patten CA, Drews AA, Myers MG, et al. Effect of depressive symptoms on smoking abstinence 

and treatment adherence among smokers with a history of alcohol dependence. Psychol Addict 

Behav 2002;16(2):135-42.

Patten CA, Martin JE, Myers MG, et al. Effectiveness of cognitive-behavioral therapy for smokers with histories of alcohol dependence and depression. J Stud Alcohol 1998;59(3):327-35.

Perkins KA, Ciccocioppo M, Conklin CA, et al. Mood influences on acute smoking responses 

are independent of nicotine intake and dose expectancy. J Abnorm Psychol 2008(1):79-93.

Piper ME, Smith SS, Schlam TR, et al. Psychiatric disorders in smokers seeking treatment for 

tobacco dependence: Relations with tobacco dependence and cessation. J Consult Clin Psychol 

2010;78(1):13-23.

Pomerleau OF, Pomerleau CS, Marks JL, et al. Prolonged nicotine patch use in quitters with past 

abstinence-induced depressed mood. J Subst Abuse Treat 2003;24(1):13-8.

Prochaska JJ, Hall SM, Tsoh JY, et al. Treating tobacco dependence in clinically depressed 

smokers: effect of smoking cessation on mental health functioning. Am J Public Health 

2008;98(3):446-8.

Rabius V, Pike KJ, Wiatrek D, et al. Comparing internet assistance for smoking cessation: 

13-month follow-up of a six-arm randomized controlled trial. J Med Internet Res 2008;10(5):e45.

Rovina N, Nikoloutsou I, Dima E, et al. Smoking cessation treatment in a real-life setting: The 

Greek experience. Therapeutic Advances in Respiratory Disease 2007;1(2):93-104.

Schippers G, Van der Meer R, Willemsen M, et al. Preliminary results from a RCT of a smoking 

cessation intervention for smokers with a history of major depression. Eur Neuropsychopharmacol 2006:S201.

Smith SS, Jorenby DE, Leischow SJ, et al. Targeting smokers at increased risk for relapse: treating women and those with a history of depression. Nicotine Tob Res 2003;5(1):99-109.

Sonne SC, Nunes EV, Jiang H, et al. The relationship between depression and smoking cessation 

outcomes in treatment-seeking substance abusers. Am J Addict 2010;19(2):111-118.

Spring B, Doran N, Pagoto S, et al. Fluoxetine, smoking, and history of major depression: A randomized controlled trial. J Consult Clin Psychol 2007;75(1):85-94. (A)
78

Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

Spring B, Hines E. Fluoxetine as a quit smoking aid for depression-prone smokers. ClinicalTrials.gov. Available at: www.clinicaltrials.gov 2004.

Spring B, Hitsman B, Pingitore R, et al. Effect of tryptophan depletion on smokers and nonsmokers with and without history of major depression. Biol Psychiatry 2007;61(1):70-7. (B)

Strong DR, Kahler CW, Leventhal AM, et al. Impact of bupropion and cognitive-behavioral 

treatment for depression on positive affect, negative affect, and urges to smoke during cessation 

treatment. Nicotine Tob Res 2009;11(10):1142-53.

Swan GE, Jack LM, Curry S, et al. Bupropion SR and counseling for smoking cessation in actual 

practice: Predictors of outcome. Nicotine Tob Res 2003;5(6):911-921.

Thorndike AN, Regan S, McKool K, et al. Depressive symptoms and smoking cessation after 

hospitalization for cardiovascular disease. Arch Intern Med 2008;168(2):186-91.

Thorndike FP, Friedman-Wheeler DG, Haaga DA. Effect of cognitive behavior therapy on smokers’ compensatory coping skills. Addict Behav 2006(9):1705-10.

Trockel M, Burg M, Jaffe A, et al. Smoking behavior postmyocardial infarction among ENRICHD trial participants: cognitive behavior therapy intervention for depression and low perceived social support compared with care as usual. Psychosom Med 2008;70(8):875-82.

Uyar M, Filiz A, Bayram N, et al. A randomized trial of smoking cessation. Medication versus 

motivation. Saudi Medical Journal 2007;28(6):922-926.

Vazquez FL, Becona E. Depression and smoking in a smoking cessation programme. J Affect 

Disord 1999;55(2-3):125-32.

Walsh Z, Epstein A, Munisamy G, et al. The impact of depressive symptoms on the efficacy of 

naltrexone in smoking cessation. J Addict Dis 2008;27(1):65-72.

Wetter DW, Fiore MC, Jorenby DE, et al. Gender differences in smoking cessation. J Consult 

Clin Psychol 1999;67(4):555-562.

Wileyto EP, Patterson F, Niaura R, et al. Recurrent event analysis of lapse and recovery in a 

smoking cessation clinical trial using bupropion. Nicotine Tob Res 2005;7(2):257-68.

Zelman DC, Brandon TH, Jorenby DE, et al. Measures of affect and nicotine dependence predict 

differential response to smoking cessation treatments. J Consult Clin Psychol 1992;60(6):943-

952.

Ziedonis D, Harris P, Brandt P, et al. Motivational enhancement therapy and nicotine replacement 

improve smoking cessation outcomes for smokers with schizophrenia or depression. Addiction 

1997:633.
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Comparative Effectiveness of Smoking Cessation Treatments 

for Patients With Depression Evidence-based Synthesis Program

APPENDIX E: ACRONYMS AND ABBREVIATIONS

AE adverse effects

am ante meridian (before noon)

BA behavioral activation

BATS behavioral activation treatment for smoking

BID two times per day

BDI-II Beck Depression Inventory-II

CBT cognitive behavioral therapy

CES-D Center for Epidemiologic Studies-Depression

CI confidence interval

CO carbon monoxide

DIS Diagnostic Interview Schedule

FTQ Fagerstrom Tolerance Questionnaire

FTND Fagerstrom Test for Nicotine Dependence

GEE generalized estimating equation

ID identification

HDRS Hamilton Depression Rating Scale

ITT intention to treat

MDD major depressive disorder

MDE major depressive episode

mg milligram or milligrams

mo month or months

ml milliliter or milliliters

N or n number

NA not applicable

NCI National Cancer Institute

ng nanogram

NRT nicotine replacement therapy

NR not reported

ns or NS not significant

OR odds ratio

p probability

pm post meridian (after noon)

POMS Profile of Mood States

ppm parts per million

RCT randomized controlled trial

SCID Structured Clinical Interview for DSM Diagnoses

SD standard deviation

SE standard error

ST standard treatment

UDD unipolar depressive disorder

vs versus

wk week or weeks

yr year or years