Carrie D. Patnode, PhD, MPH; Jillian T. Henderson, PhD, MPH; Jamie H. Thompson, MPH; Caitlyn A. Senger, MPH; Stephen P. Fortmann, MD; Evelyn P. Whitlock, MD, MPH
Note: This review was done by the Kaiser Permanente Research Affiliates Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality. Agency for Healthcare Research and Quality staff provided oversight for the project and assisted in the external review of the companion draft evidence synthesis.
Acknowledgment: The authors thank the Agency for Healthcare Research and Quality and members of the U.S. Preventive Services Task Force. They also thank the following persons and groups for providing expert or federal partner review of the report: Catherine Chamberlain, MScPHP, MPH, BaSc; Michael Fiore, MD, MPH, MBA; Rashelle Hayes, PhD, MS; Jennifer McClure, PhD; Nancy Rigotti, MD; the Centers for Disease Control and Prevention's National Center for Chronic Disease Prevention and Health Promotion and National Institute for Occupational Safety and Health; and the National Cancer Institute. The authors also thank Smyth Lai, MLS; Kevin Lutz, MFA; and Keshia Bigler at Kaiser Permanente Center for Health Research.
Financial Support: By the Agency for Healthcare Research and Quality (contract HHSA-290-2012-00015-I).
Disclosures: Dr. Patnode reports grants from the Agency for Healthcare Research and Quality (AHRQ) during the conduct of the study. Ms. Henderson reports grants from AHRQ during the conduct of the study. Ms. Thompson reports grants from AHRQ during the conduct of the study. Ms. Senger reports grants from AHRQ during the conduct of the study. Dr. Fortmann reports grants from AHRQ during the conduct of the study. Dr. Whitlock reports grants from AHRQ during the conduct of the study. Authors not listed here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0171.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Reprints are available from the Agency for Healthcare Research and Quality Web site (www.ahrq.gov).
Current Author Addresses: Drs. Patnode, Henderson, Fortmann, and Whitlock; Ms. Thompson; and Ms. Senger: Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227.
Author Contributions: Conception and design: C.D. Patnode.
Analysis and interpretation of the data: C.D. Patnode, J.T. Henderson, S.P. Fortmann.
Drafting of the article: C.D. Patnode, J.T. Henderson, S.P. Fortmann.
Critical revision of the article for important intellectual content: C.D. Patnode, J.T. Henderson, S.P. Fortmann, E.P. Whitlock.
Final approval of the article: C.D. Patnode, J.T. Henderson, J.H. Thompson, C.A. Senger, S.P. Fortmann, E.P. Whitlock.
Provision of study materials or patients: C.D. Patnode.
Statistical expertise: C.D. Patnode, J.T. Henderson.
Obtaining of funding: E.P. Whitlock.
Administrative, technical, or logistic support: C.D. Patnode, J.H. Thompson, C.A. Senger, E.P. Whitlock.
Collection and assembly of data: C.D. Patnode, J.T. Henderson, J.H. Thompson, C.A. Senger, S.P. Fortmann.
Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;163:608-621. doi: 10.7326/M15-0171
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Published: Ann Intern Med. 2015;163(8):608-621.
Published at www.annals.org on 22 September 2015
Tobacco use is the leading cause of preventable death in the United States.
To review the effectiveness and safety of pharmacotherapy and behavioral interventions for tobacco cessation.
5 databases and 8 organizational Web sites were searched through 1 August 2014 for systematic reviews, and PubMed was searched through 1 March 2015 for trials on electronic nicotine delivery systems.
Two reviewers examined 114 articles to identify English-language reviews that reported health, cessation, or adverse outcomes.
One reviewer abstracted data from good- and fair-quality reviews, and a second checked for accuracy.
54 reviews were included. Behavioral interventions increased smoking cessation at 6 months or more (physician advice had a pooled risk ratio [RR] of 1.76 [95% CI, 1.58 to 1.96]). Nicotine replacement therapy (RR, 1.60 [CI, 1.53 to 1.68]), bupropion (RR, 1.62 [CI, 1.49 to 1.76]), and varenicline (RR, 2.27 [CI, 2.02 to 2.55]) were also effective for smoking cessation. Combined behavioral and pharmacotherapy interventions increased cessation by 82% compared with minimal intervention or usual care (RR, 1.82 [CI, 1.66 to 2.00]). None of the drugs were associated with major cardiovascular adverse events. Only 2 trials addressed efficacy of electronic cigarettes for smoking cessation and found no benefit. Among pregnant women, behavioral interventions benefited cessation and perinatal health; effects of nicotine replacement therapy were not significant.
Evidence published after each review's last search date was not included.
Behavioral and pharmacotherapy interventions improve rates of smoking cessation among the general adult population, alone or in combination. Data on the effectiveness and safety of electronic nicotine delivery systems are limited.
Agency for Healthcare Research and Quality.
KQ = key question.
Appendix Table 1. Criteria for Choosing the Primary Existing Systematic Reviews
Summary of evidence search and selection.
* 2 studies included both adults and pregnant women.
†Reviews can be counted in multiple intervention areas.
Table 1. Characteristics of Included Systematic Reviews (n = 54), by Population, Intervention, and Last Search Date
Table 2. Summary of Evidence for the General Adult Population
Appendix Table 2. Summary of Smoking Abstinence Results From Reviews of Behavioral Counseling and Pharmacotherapy Interventions for Smoking Cessation Among Adults, by Type of Intervention
Appendix Table 3. Efficacy and Safety of the Use of ENDS for Smoking Cessation
Table 3. Summary of Evidence for Pregnant Women
Appendix Table 4. Summary of Perinatal Health Outcome Results of Behavioral Interventions for Smoking Cessation Among Pregnant Women*
Appendix Table 5. Summary of Smoking Abstinence Results From Reviews of Interventions for Smoking Cessation Among Pregnant Women
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Alain Braillon, Susan Bewley
University Hospital, Amiens, France, Kings College London
October 22, 2015
USPSTF incomplete review fails pregnant women and their doctors.
With its ‘review of reviews’ methodology, the normally respected US Preventive Services Task Force (1) failed to critically analyse a recent negative trial (2) and missed a major well designed trial on Nicotine Replacement Therapy (NRT).(3)
The authors included a trial of low dose nicotine patches alone (16 mg nicotine, 16 hours delivery) which hardly surprisingly failed to decrease withdrawal symptoms and craving vs. placebo, (2) as pregnant women are highly dependent on nicotine due to increased metabolism.(4)
Combining patches with faster acting forms of nicotine replacement therapy as a ‘belt and braces’ strategy works substantially better than patches alone, understandably related to the pharmokinetics. A 2013 trial was overlooked that showed this strategy is also evidence-based during pregnancy where it doubles the odds ratio of quitting.(3)
People should not fear nicotine more than carbon monoxide and the deleterious products of combustion: plasma nicotine levels are steady and lower with a 21 mg patch than with smoking, and peaks are avoided. Typical steady-state plasma nicotine concentrations with nicotine patches range from 10 to 20 ng/ml while smoking a cigarette results in a mean arterial plasma concentrations of about 30 ng/ml, not accounting for the peaks.(5) Moreover, as NRT greatly suppresses craving, occasional cigarette smoking with a patch is less deleterious than smoking without a patch because there is no compensatory smoking (ie more intense smoking) but a decreased uptake.
Healthcare professionals who want to truly help pregnant smokers and their expected children need better training in basic pharmacology (dose effects, pharmacokinetics, toxicology), basic support and cognitive behavioural therapies.
1 Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral counseling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: A Review of reviews for the U.S. Preventive Services Task Force. Ann Intern Med 2015. Online Sep 22. doi: 10.7326/M15-0171.
2 Brose LS, McEwen A, West R. Association between nicotine replacement therapy use in pregnancy and smoking cessation. Drug and Alchohol Dependence 2013;132:660-4.
3 Berlin I, Grangé G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised,placebo controlled, multicentre trial of efficacy. BMJ 2014;348:g1622
4 Koren G, Blanchette P, Lubetzky A, Kramer M. Hair nicotine: cotinine metabolic ratio in pregnant women: a new method to study metabolism in late pregnancy. Ther Drug Monit 2008 ;30:246-8.
5 Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009;192:29-60.
Jillian T. Henderson, PhD, MPH, Carrie D. Patnode, PhD, MPH, Stephen P. Fortmann, MD
December 2, 2015
Drs. Braillon and Bewley expressed concerns about our synthesis of the evidence related to the effectiveness of pharmacotherapy for tobacco cessation among pregnant women as part of our recently published systematic review for the U.S. Preventive Services Task Force (1). We offer reassurance that our report did not inadvertently fail to consider the two studies cited in their letter. The study by Brose et al. (2) was not included in our review because it was not a randomized controlled trial. Following usual U.S. Preventive Services Task Force methodological guidance, we prespecified only the inclusion of randomized controlled trials. Indeed, Brose and colleagues concluded that while their correlational findings are encouraging, RCT confirmation is needed. The second trial by Berlin et al. (3) was identified in a primary search, critically appraised as part of our systematic review process, and included in our analysis (see publication reference number 77 and Appendix Table 5). While it is possible that null findings may be related to the nicotine dosage used, Berlin et al. did match the patch dose to baseline saliva cotinine level and none of the available trials in pregnant women used the higher 21mg dose proposed by Braillon and Bewley. It is clear that more research is needed on the use of NRT for smoking cessation among pregnant women. If higher doses of nicotine replacement are studied, however, it will remain important to document fetal effects. It may seem obvious that nicotine in the absence of combustion products is safer than smoking, but the complex metabolism of pregnancy, and systemic response to changes in smoking behaviors during pregnancy are not well enough understood to apply findings from studies in non-pregnant adults to pregnant women. Reference List (1) Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;163:608-21. [PMID: 26389650] (2) Brose LS, McEwen A, West R. Association between nicotine replacement therapy use in pregnancy and smoking cessation. Drug & Alcohol Dependence. 2013;132:660-664. [PMID: 23680076] (3) Berlin I, Grange G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622. [PMID: 24627552]
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