Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial
Background:
Extended use of combined pharmacotherapies to treat tobacco dependence may increase smoking abstinence; few studies have examined their effectiveness. The objective of this study was to evaluate smoking abstinence with standard nicotine patch (NRT), extended use of combined formulations of nicotine replacement therapy (NRT+), or varenicline (VR).
Methods:
A total of 737 smokers, including those with medical and psychiatric comorbidities, were randomly assigned to one of the above three treatment conditions. The NRT group received 10 weeks of patches (21 mg daily maximum); the NRT+ group received patches (35 mg daily maximum) and gum or inhaler for up to 22 weeks; and the VR group received 1 mg twice daily for up to 24 weeks (22 weeks post target quit date). All participants also received six standardized 15-minute smoking cessation counseling sessions by nurses experienced in tobacco dependence treatment. The primary outcome was carbon monoxide-confirmed continuous abstinence rates (CAR) from weeks 5–52. Secondary outcomes were: CAR from weeks 5–10 and 5–22, and carbon monoxide-confirmed 7-day point prevalence (7PP) at weeks 10, 22, and 52. Adjusted and unadjusted logistic regression analyses were conducted using intention-to-treat procedures.
Results:
The CARs for weeks 5–52 were 10.0 %, 12.4 %, and 15.3 % in the NRT, NRT+, and VR groups, respectively; no group differences were observed. Results with 7PP showed that VR was superior to NRT at week 52 (odds ratio (OR), 1.84; 97.5 % Confidence Interval (CI), 1.04–3.26) in the adjusted intention-to-treat analysis. Those in the VR group had higher CAR at weeks 5–22 (OR, 2.01; CI, 1.20–3.36) than those in the NRT group. Results with 7PP revealed that both NRT+ (OR, 1.72; CI, 1.04–2.85) and VR (OR, 1.96; CI, 1.20–3.23) were more effective than NRT at 22 weeks. As compared to NRT monotherapy, NRT+ and VR produced significant increases in CAR for weeks 5–10 (OR, 1.52; CI, 1.00–2.30 and OR, 1.58; CI, 1.04–2.39, respectively); results were similar, but somewhat stronger, when 7PP was used at 10 weeks (OR, 1.57; CI, 1.03–2.41 and OR, 1.79; CI, 1.17–2.73, respectively). All medications were well tolerated, but participants in the VR group experienced more fatigue, digestive symptoms (e.g., nausea, diarrhea), and sleep-related concerns (e.g., abnormal dreams, insomnia), but less dermatologic symptoms than those in the NRT or NRT+ groups. The frequency of serious adverse events did not differ between groups.
Conclusions:
Flexible and combination NRT and varenicline enhance success in the early phases of quitting. Varenicline improves abstinence in the medium term; however, there is no clear evidence that either varenicline or flexible, dual-form NRT increase quit rates in the long-term when compared to NRT monotherapy.
Trial registration:
ClinicalTrials.gov Identifier: NCT01623505; Retrospectively registered on July 13, 2011
Keywords:
Smoking cessation, RCT, Efficacy, Intervention, Extended treatment
Autoři:
Heather E. Tulloch 1,2,3*; Andrew L. Pipe 1,2; Charl Els 4; Matthew J. Clyde 1,3; Robert D. Reid 1,2
Působiště autorů:
Division of Prevention and Rehabilitation, University of Ottawa Heart Institute, 0 Ruskin Street, Ottawa, ON K1Y W7, Canada.
1; Faculty of Medicine, University of Ottawa, Ottawa, Canada.
2; School of Psychology, University of Ottawa, Ottawa, Canada.
3; Department of Psychiatry, 1E1 Walter Mackenzie Health Sciences Centre, University of Alberta, Edmonton, AB T6G 2R7, Canada.
4
Vyšlo v časopise:
BMC Medicine 2016, 14:80
Kategorie:
Research article
prolekare.web.journal.doi_sk:
https://doi.org/10.1186/s12916-016-0626-2
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0626-2
Souhrn
Background:
Extended use of combined pharmacotherapies to treat tobacco dependence may increase smoking abstinence; few studies have examined their effectiveness. The objective of this study was to evaluate smoking abstinence with standard nicotine patch (NRT), extended use of combined formulations of nicotine replacement therapy (NRT+), or varenicline (VR).
Methods:
A total of 737 smokers, including those with medical and psychiatric comorbidities, were randomly assigned to one of the above three treatment conditions. The NRT group received 10 weeks of patches (21 mg daily maximum); the NRT+ group received patches (35 mg daily maximum) and gum or inhaler for up to 22 weeks; and the VR group received 1 mg twice daily for up to 24 weeks (22 weeks post target quit date). All participants also received six standardized 15-minute smoking cessation counseling sessions by nurses experienced in tobacco dependence treatment. The primary outcome was carbon monoxide-confirmed continuous abstinence rates (CAR) from weeks 5–52. Secondary outcomes were: CAR from weeks 5–10 and 5–22, and carbon monoxide-confirmed 7-day point prevalence (7PP) at weeks 10, 22, and 52. Adjusted and unadjusted logistic regression analyses were conducted using intention-to-treat procedures.
Results:
The CARs for weeks 5–52 were 10.0 %, 12.4 %, and 15.3 % in the NRT, NRT+, and VR groups, respectively; no group differences were observed. Results with 7PP showed that VR was superior to NRT at week 52 (odds ratio (OR), 1.84; 97.5 % Confidence Interval (CI), 1.04–3.26) in the adjusted intention-to-treat analysis. Those in the VR group had higher CAR at weeks 5–22 (OR, 2.01; CI, 1.20–3.36) than those in the NRT group. Results with 7PP revealed that both NRT+ (OR, 1.72; CI, 1.04–2.85) and VR (OR, 1.96; CI, 1.20–3.23) were more effective than NRT at 22 weeks. As compared to NRT monotherapy, NRT+ and VR produced significant increases in CAR for weeks 5–10 (OR, 1.52; CI, 1.00–2.30 and OR, 1.58; CI, 1.04–2.39, respectively); results were similar, but somewhat stronger, when 7PP was used at 10 weeks (OR, 1.57; CI, 1.03–2.41 and OR, 1.79; CI, 1.17–2.73, respectively). All medications were well tolerated, but participants in the VR group experienced more fatigue, digestive symptoms (e.g., nausea, diarrhea), and sleep-related concerns (e.g., abnormal dreams, insomnia), but less dermatologic symptoms than those in the NRT or NRT+ groups. The frequency of serious adverse events did not differ between groups.
Conclusions:
Flexible and combination NRT and varenicline enhance success in the early phases of quitting. Varenicline improves abstinence in the medium term; however, there is no clear evidence that either varenicline or flexible, dual-form NRT increase quit rates in the long-term when compared to NRT monotherapy.
Trial registration:
ClinicalTrials.gov Identifier: NCT01623505; Retrospectively registered on July 13, 2011
Keywords:
Smoking cessation, RCT, Efficacy, Intervention, Extended treatment
Zdroje
1. US Department of Health and Human Services. The health consequences of smoking—50 years of progress: A Report of the Surgeon General. Atlanta: USDHHS, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.
2. Jha P, Ranson MK, Nguyen SN, Yach D. Estimates of global and regional smoking prevalence in 1995, by age and sex. Am J Public Health. 2002;92:1002–6.
3. Storr CL, Cheng H, Alonso J, et al. Smoking estimates from around the world: Data from the first 17 participating countries in the World Mental Health Survey Consortium. Tob Control. 2010;19:65–74.
4. Borland R, Li L, Driezen P, et al. Cessation assistance reported by smokers in 15 countries participating in the International Tobacco Control (ITC) policy evaluation surveys. Addiction. 2012;107:197–205.
5. Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2004;99:29–38.
6. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013;5:CD009329.
7. Fiore M, Jaen C, Baker T. Treating tobacco use and dependence: 2008 update: Clinical Practice Guideline. Rockville: US Department of Health and Human Services, Public Health Service; 2008. Report No.: 1437906621.
8. Mills EJ, Wu P, Lockhart I, Thorlund K, Puhan M, Ebbert JO. Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: A systematic review and multiple treatment meta-analysis. Ann Med. 2012;44:588–97.
9. Aubin HJ, Bobak A, Britton JR, et al. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax. 2008;63:717–24.
10. Piper ME, Smith SS, Schlam TR, et al. A randomized placebo-controlled clinical trial of five smoking cessation pharmacotherapies. Arch Gen Psychiatry. 2009;66:1253.
11. Tsukahara H, Noda K, Saku K. A randomized controlled open comparative trial of varenicline vs nicotine patch in adult smokers: efficacy, safety and withdrawal symptoms (the VN-SEESAW study). Circ J. 2010;74:771.
12. Baker T, Piper M, Stein J, Smith S, Bolt D, Fraser D, et al. Effects of nicotine patch vs varenicline vs combination nicotine replacement therapy on smoking cessation at 26 weeks: A randomized clinical trial. JAMA. 2016;315(4):371–9.
13. Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease a randomized trial. Circulation. 2010;121:221–9.
14. Steinberg MB, Randall J, Greenhaus S, Schmelzer AC, Richardson DL, Carson JL. Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline. Addict Behav. 2011;36:1127–32.
15. Tashkin DP, Rennard S, Hays JT, Ma W, Lawrence D, Lee TC. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest. 2011;139:591–9.
16. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856.
17. Anthenelli RM, Morris C, Ramey TS, et al. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med. 2013;159:390–400.
18. Hong LE, Thaker GK, McMahon RP, et al. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 2011;68:1195–206.
19. McClure JB, Swan GE, Catz SL, et al. Smoking outcome by psychiatric history after behavioral and varenicline treatment. J Subst Abuse Treat. 2010;38:394–402.
20. Weiner E, Buchholz A, Coffay A, et al. Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res. 2011;129:94–5.
21. Williams JM, Anthenelli RM, Morris CD, et al. A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2012;73:654–60. doi:10.4088/JCP.11m07522.
22. Wu BS, Weinberger AH, Mancuso E, et al. A preliminary feasibility study of varenicline for smoking cessation in bipolar disorder. J Dual Diagnosis. 2012;8:131–2.
23. Tulloch H, Pipe A, Els C, et al. Flexible and extended dosing of nicotine replacement therapy or varenicline in comparison to fixed dose nicotine replacement therapy for smoking cessation: Rationale, methods and participant characteristics of the FLEX trial. Contemp Clin Trials. 2014;38:304–13.
24. Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43:289.
25. Sheehan DV, Lecrubier Y, Harnett-Sheehan K, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar G, The M.I.N.I. International Neuropsychiatric Interview (M.I.N.I.). The Development and Validation of a Structured Diagnostic Psychiatric Interview. J Clin Psychiatry. 1998;59(suppl 20):22–33.
26. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom K-O. The Fagerström Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991;86:1119–27.
27. West R, Hajek P, Stead L, Stapleton J. Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction. 2005;100:299–303.
28. Hedeker D, Mermelstein RJ, Demirtas H. Analysis of binary outcomes with missing data: missing = smoking, last observation carried forward, and a little multiple imputation. Addiction. 2007;102:1564–73.
29. Gibbons RD, Mann JJ. Varenicline, smoking cessation, and neuropsychiatric adverse events. Am J Psychiatry. 2013;170:1460–7.
30. Gunnell D, Irvine D, Wise L, Davies C, Martin RM. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ. 2009;339:b3805.
31. Pasternak B, Svanström H, Hviid A. Use of varenicline versus bupropion and risk of psychiatric adverse events. Addiction. 2013;108:1336–43.
32. Thomas KH, Martin RM, Davies NM, Metcalfe C, Windmeijer F, Gunnell D. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study. BMJ. 2013;347:f5704.
33. Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313:687–94.
34. Costa ML, Cohen JE, Chaiton MO, Ip D, McDonald P, Ferrence R. “Hardcore” definitions and their application to a population-based sample of smokers. Nicotine Tob Res. 2010;12:860–4.
35. Warner KE, Burns DM. Hardening and the hard-core smoker: concepts, evidence, and implications. Nic Tob Res. 2003;5:37–48.
36. LeLorier J, Grégoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. NEJM. 1997;337:536–42.
37. Schnoll R, Goelz P, Veluz-Wilkins A, Blazekovic S, Powers L, Leone F, et al. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Int Med. 2015;175(4):504–11.
Článok vyšiel v časopise
BMC Medicine
2016 Číslo 80
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Profylaxe infekční endokarditidy ve stomatologii
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
Najčítanejšie v tomto čísle