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. 2019 Apr 18;4(4):CD013308.
doi: 10.1002/14651858.CD013308.

Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation

Nicola Lindson  1 , Samantha C Chepkin, Weiyu Ye, Thomas R Fanshawe, Chris Bullen, Jamie Hartmann-Boyce
Affiliations

Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation

Nicola Lindson et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes to ease the transition from cigarette smoking to abstinence. It works by reducing the intensity of craving and withdrawal symptoms. Although there is clear evidence that NRT used after smoking cessation is effective, it is unclear whether higher doses, longer durations of treatment, or using NRT before cessation add to its effectiveness.

Objectives: To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long-term smoking cessation, compared to one another.

Search methods: We searched the Cochrane Tobacco Addiction Group trials register, and trial registries for papers mentioning NRT in the title, abstract or keywords. Date of most recent search: April 2018.

Selection criteria: Randomized trials in people motivated to quit, comparing one type of NRT use with another. We excluded trials that did not assess cessation as an outcome, with follow-up less than six months, and with additional intervention components not matched between arms. Trials comparing NRT to control, and trials comparing NRT to other pharmacotherapies, are covered elsewhere.

Data collection and analysis: We followed standard Cochrane methods. Smoking abstinence was measured after at least six months, using the most rigorous definition available. We extracted data on cardiac adverse events (AEs), serious adverse events (SAEs), and study withdrawals due to treatment. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate, using a Mantel-Haenszel fixed-effect model.

Main results: We identified 63 trials with 41,509 participants. Most recruited adults either from the community or from healthcare clinics. People enrolled in the studies typically smoked at least 15 cigarettes a day. We judged 24 of the 63 studies to be at high risk of bias, but restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results, apart from in the case of the preloading comparison. There is high-certainty evidence that combination NRT (fast-acting form + patch) results in higher long-term quit rates than single form (RR 1.25, 95% CI 1.15 to 1.36, 14 studies, 11,356 participants; I2 = 4%). Moderate-certainty evidence, limited by imprecision, indicates that 42/44 mg are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93 to 1.29, 5 studies, 1655 participants; I2 = 38%), and that 21 mg are more effective than 14 mg (24-hour) patches (RR 1.48, 95% CI 1.06 to 2.08, 1 study, 537 participants). Moderate-certainty evidence (again limited by imprecision) also suggests a benefit of 25 mg over 15 mg (16-hour) patches, but the lower limit of the CI encompassed no difference (RR 1.19, 95% CI 1.00 to 1.41, 3 studies, 3446 participants; I2 = 0%). Five studies comparing 4 mg gum to 2 mg gum found a benefit of the higher dose (RR 1.43, 95% CI 1.12 to 1.83, 5 studies, 856 participants; I2 = 63%); however, results of a subgroup analysis suggest that only smokers who are highly dependent may benefit. Nine studies tested the effect of using NRT prior to quit day (preloading) in comparison to using it from quit day onward; there was moderate-certainty evidence, limited by risk of bias, of a favourable effect of preloading on abstinence (RR 1.25, 95% CI 1.08 to 1.44, 9 studies, 4395 participants; I2 = 0%). High-certainty evidence from eight studies suggests that using either a form of fast-acting NRT or a nicotine patch results in similar long-term quit rates (RR 0.90, 95% CI 0.77 to 1.05, 8 studies, 3319 participants; I2 = 0%). We found no evidence of an effect of duration of nicotine patch use (low-certainty evidence); 16-hour versus 24-hour daily patch use; duration of combination NRT use (low- and very low-certainty evidence); tapering of patch dose versus abrupt patch cessation; fast-acting NRT type (very low-certainty evidence); duration of nicotine gum use; ad lib versus fixed dosing of fast-acting NRT; free versus purchased NRT; length of provision of free NRT; ceasing versus continuing patch use on lapse; and participant- versus clinician-selected NRT. However, in most cases these findings are based on very low- or low-certainty evidence, and are the findings from single studies.AEs, SAEs and withdrawals due to treatment were all measured variably and infrequently across studies, resulting in low- or very low-certainty evidence for all comparisons. Most comparisons found no evidence of an effect on cardiac AEs, SAEs or withdrawals. Rates of these were low overall. Significantly more withdrawals due to treatment were reported in participants using nasal spray in comparison to patch in one trial (RR 3.47, 95% CI 1.15 to 10.46, 922 participants; very low certainty) and in participants using 42/44 mg patches in comparison to 21/22 mg patches across two trials (RR 4.99, 95% CI 1.60 to 15.50, 2 studies, 544 participants; I2 = 0%; low certainty).

Authors' conclusions: There is high-certainty evidence that using combination NRT versus single-form NRT, and 4 mg versus 2 mg nicotine gum, can increase the chances of successfully stopping smoking. For patch dose comparisons, evidence was of moderate certainty, due to imprecision. Twenty-one mg patches resulted in higher quit rates than 14 mg (24-hour) patches, and using 25 mg patches resulted in higher quit rates than using 15 mg (16-hour) patches, although in the latter case the CI included one. There was no clear evidence of superiority for 42/44 mg over 21/22 mg (24-hour) patches. Using a fast-acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate-certainty evidence that using NRT prior to quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is of low and very low certainty. New studies should ensure that AEs, SAEs and withdrawals due to treatment are both measured and reported.

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Conflict of interest statement

CB was involved in two included trials of NRT preloading (Bullen 2010; Walker 2011). CB did not extract the data or conduct 'Risk of bias' assessment for this trial. CB has no known competing interests in relation to the work in question. CB has received honoraria for board memberships, visiting academic work at other universities and consultancy fees for some research projects; however, these are not deemed to result in conflicts with the current work.

JHB: None known.

NL is employed by the University of Oxford to work as a Managing Editor for the Cochrane Tobacco Addiction Review Group. Core infrastructure funding for the Cochrane Tobacco Addiction Group is provided by the NIHR to the University of Oxford. NL was involved in an included trial of NRT preloading (Preloading Investigators 2018). NL did not extract the data or conduct 'Risk of bias' assessment for this trial.

SC: None known.

TRF: None known.

WY: None known.

Figures

1
1
Flow diagram for the 2018 search update only
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 4 Combination versus single form NRT, outcome: 4.1 Smoking cessation.
1.1
1.1. Analysis
Comparison 1 Patch dose, Outcome 1 Smoking cessation.
1.2
1.2. Analysis
Comparison 1 Patch dose, Outcome 2 Fast or irregular heartbeat.
1.3
1.3. Analysis
Comparison 1 Patch dose, Outcome 3 Myocardial infarction.
1.4
1.4. Analysis
Comparison 1 Patch dose, Outcome 4 Overall SAEs.
1.5
1.5. Analysis
Comparison 1 Patch dose, Outcome 5 Treatment withdrawals.
2.1
2.1. Analysis
Comparison 2 Duration of patch therapy, Outcome 1 Smoking cessation.
2.2
2.2. Analysis
Comparison 2 Duration of patch therapy, Outcome 2 Overall SAEs.
2.3
2.3. Analysis
Comparison 2 Duration of patch therapy, Outcome 3 Treatment withdrawals.
3.1
3.1. Analysis
Comparison 3 Effect of tapering patch dose, Outcome 1 Smoking cessation.
3.2
3.2. Analysis
Comparison 3 Effect of tapering patch dose, Outcome 2 Treatment withdrawals.
4.1
4.1. Analysis
Comparison 4 Combination versus single‐form NRT, Outcome 1 Smoking cessation.
4.2
4.2. Analysis
Comparison 4 Combination versus single‐form NRT, Outcome 2 Any cardiac AE.
4.3
4.3. Analysis
Comparison 4 Combination versus single‐form NRT, Outcome 3 Overall SAEs.
4.4
4.4. Analysis
Comparison 4 Combination versus single‐form NRT, Outcome 4 Treatment withdrawals.
5.1
5.1. Analysis
Comparison 5 Duration of combination therapy, Outcome 1 Smoking cessation.
5.2
5.2. Analysis
Comparison 5 Duration of combination therapy, Outcome 2 Overall SAEs.
6.1
6.1. Analysis
Comparison 6 Fast‐acting NRT versus patch, Outcome 1 Smoking cessation.
6.2
6.2. Analysis
Comparison 6 Fast‐acting NRT versus patch, Outcome 2 Cardiac AEs.
6.3
6.3. Analysis
Comparison 6 Fast‐acting NRT versus patch, Outcome 3 Overall SAEs.
6.4
6.4. Analysis
Comparison 6 Fast‐acting NRT versus patch, Outcome 4 Treatment withdrawals.
7.1
7.1. Analysis
Comparison 7 Type of fast‐acting NRT, Outcome 1 Smoking cessation.
8.1
8.1. Analysis
Comparison 8 4 mg versus 2 mg gum, Outcome 1 Smoking cessation.
8.2
8.2. Analysis
Comparison 8 4 mg versus 2 mg gum, Outcome 2 Palpitations.
8.3
8.3. Analysis
Comparison 8 4 mg versus 2 mg gum, Outcome 3 Treatment withdrawals.
9.1
9.1. Analysis
Comparison 9 Fixed versus ad lib dose schedule, Outcome 1 Smoking cessation.
9.2
9.2. Analysis
Comparison 9 Fixed versus ad lib dose schedule, Outcome 2 Overall SAEs.
9.3
9.3. Analysis
Comparison 9 Fixed versus ad lib dose schedule, Outcome 3 Treatment withdrawals.
10.1
10.1. Analysis
Comparison 10 Preloading versus standard use, Outcome 1 Smoking cessation.
10.2
10.2. Analysis
Comparison 10 Preloading versus standard use, Outcome 2 Palpitations.
10.3
10.3. Analysis
Comparison 10 Preloading versus standard use, Outcome 3 Cardiac AEs.
10.4
10.4. Analysis
Comparison 10 Preloading versus standard use, Outcome 4 Cardiac SAEs.
10.5
10.5. Analysis
Comparison 10 Preloading versus standard use, Outcome 5 Overall SAEs.
10.6
10.6. Analysis
Comparison 10 Preloading versus standard use, Outcome 6 Treatment withdrawals.
11.1
11.1. Analysis
Comparison 11 Free NRT versus purchased NRT, Outcome 1 Smoking cessation.
11.2
11.2. Analysis
Comparison 11 Free NRT versus purchased NRT, Outcome 2 Cardiac AEs.
12.1
12.1. Analysis
Comparison 12 Duration of free NRT, Outcome 1 Smoking cessation.
13.1
13.1. Analysis
Comparison 13 Other comparisons, Outcome 1 Smoking cessation.
13.2
13.2. Analysis
Comparison 13 Other comparisons, Outcome 2 Midsternal pressure.
13.3
13.3. Analysis
Comparison 13 Other comparisons, Outcome 3 Cardiac AEs.
13.4
13.4. Analysis
Comparison 13 Other comparisons, Outcome 4 Overall SAEs.
13.5
13.5. Analysis
Comparison 13 Other comparisons, Outcome 5 Treatment withdrawals.
See this image and copyright information in PMC

References

References to studies included in this review

Abdullah 2013 {published data only}
    1. Abdullah AS, Hedley AJ, Chan SS, Lam TH. A randomized controlled trial of two different lengths of nicotine replacement therapy for smoking cessation. BioMed Research International 2013;Epub(961751):1‐9. [DOI: 10.1155/2013/961751] - DOI - PMC - PubMed
Baker 2016 {published and unpublished data}
    1. Baker TB, Piper ME, Stein JH. 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. - PMC - PubMed
    1. NCT01553084. A comparative effectiveness and long term health study in Wisconsin smokers (NHLBI‐RO1). clinicaltrials.gov/ct2/show/study/NCT01553084?view=record (first received 13 March 2012).
Blondal 1999 {published data only}
    1. Blondal T, Gudmundsson LJ, Olafsdottir I, Gustavsson G, Westin A. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. BMJ 1999;318(7179):285‐9. - PMC - PubMed
    1. Blondal T, Ludviksdottir D, Gudmundsson L, Olafsdottir I, Gustavsson G, Westin A. Efficacy of nicotine nasal spray added to transdermal nicotine patches in smoking cessation [Abstract]. 10th World Conference on Tobacco or Health; 1997 08 24‐28; Beijing, China. 1997:48.
Bohadana 2000 {published data only}
    1. Bohadana A, Nilsson F, Rasmussen T, Martinet Y. Gender differences in quit rates following smoking cessation with combination nicotine therapy: influence of baseline smoking behavior. Nicotine & Tobacco Research 2003;5(1):111‐6. - PubMed
    1. Bohadana A, Nilsson F, Rasmussen T, Martinet Y. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation ‐ A randomized, double‐blind, placebo‐controlled trial. Archives of Internal Medicine 2000;160(20):3128‐34. - PubMed
    1. Bohadana AB, Nilsson F, Martinet Y. Nicotine inhaler and nicotine patch: a combination therapy for smoking cessation. Nicotine & Tobacco Research 1999;1(2):189.
Bolin 1999 {published data only}
    1. Bolin LJ, Antonuccio DO, Follette WC, Krumpe P. Transdermal nicotine: the long and the short of it. Psychology of Addictive Behaviors 1999;13:152‐6.
Bolliger 2007 {published data only}
    1. Bolliger CT, Biljion X, Axelsson A. A nicotine mouth spray for smoking cessation: a pilot study of preference, safety and efficacy. Respiration 2007;74(2):196‐201. - PubMed
Bullen 2010 {published data only}
    1. Bullen C, Howe C, Lin RB, Grigg M, Laugesen M, McRobbie H, et al. Pre‐cessation nicotine replacement therapy: pragmatic randomized trial. Addiction 2010;105(8):1474‐83. - PubMed
Burns 2016 {published data only}
    1. Burns EK, Hood NE, Goforth E, Levinson AH. Randomised trial of two nicotine patch protocols distributed through a state quitline. Tobacco Control 2016;25(2):218‐23. [DOI: 10.1136/tobaccocontrol-2014-051843] - DOI - PubMed
Caldwell 2014 {published and unpublished data}
    1. Caldwell BO, Adamson SJ, Crane J. Combination rapid‐acting nicotine mouth spray and nicotine patch therapy in smoking cessation. Nicotine & Tobacco Research 2014;16(10):1356‐64. [DOI: 10.1093/ntr/ntu084] - DOI - PubMed
Caldwell 2016 {published data only}
    1. Caldwell BO, Crane J. Combination nicotine metered dose inhaler and nicotine patch for smoking cessation: A randomized controlled trial. Nicotine & Tobacco Research 2016;18(10):1944‐51. [DOI: 10.1093/ntr/ntw093] - DOI - PubMed
CEASE 1999 {published data only}
    1. Tønnesen P, Paoletti P, Gustavsson G, Russell MA, Saracci R, Gulsvik A, et al. Higher dosage nicotine patches increase one‐year smoking cessation rates: Results from the European CEASE trial. European Respiratory Journal 1999;13(2):238‐46. - PubMed
Cooney 2009 {published data only}
    1. Cooney NL, Cooney JL, Perry BL, Carbone M, Cohen EH, Steinberg H, et al. Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum. Addiction 2009;104(9):1588‐96. - PMC - PubMed
Croghan 2003 {published data only}
    1. Croghan GA, Hurt RD, Croghan IT, Sloan J, Novotny P, Loprinzi C. Comparison of a 15 mg transdermal nicotine patch alone versus nicotine nasal spray alone versus both for smoking cessation. Journal of Addictive Diseases 1998;17:121.
    1. Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL, et al. Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: A minimal intervention, randomized multicenter trial in a nonspecialized setting. Nicotine & Tobacco Research 2003;5(2):181‐7. - PubMed
Cummings 2011 {published data only}
    1. Cummings KM, Hyland A, Carlin‐Menter S, Mahoney MC, Willett J, Juster HR. Costs of giving out free nicotine patches through a telephone quit line. Journal of Public Health Management & Practice 2011;17(3):E16‐23. - PubMed
Dale 1995 {published data only}
    1. Dale LC, Hurt RD, Offord KP, Lawson GM, Croghan IT, Schroeder DR. High‐dose nicotine patch therapy ‐ percentage of replacement and smoking cessation. JAMA 1995;274(17):1353‐8. - PubMed
    1. Dale LC, Schroeder DR, Wolter TD, Croghan IT, Hurt RD, Offord KP. Weight change after smoking cessation using variable doses of transdermal nicotine replacement. Journal of General Internal Medicine 1998;13(1):9‐15. - PMC - PubMed
Daughton 1991 {published data only}
    1. Daughton DM, Heatley SA, Prendergast JJ, Causey D, Knowles M, Rolf CN, et al. Effect of transdermal nicotine delivery as an adjunct to low‐intervention smoking cessation therapy. A randomized, placebo‐controlled, double‐blind study. Archives of Internal Medicine 1991;151(4):749‐52. - PubMed
    1. Daughton DM, Heatley SA, Prendergast JJ, Causey D, Knowles M, Rolf CN, et al. Effects of transdermal nicotine as an adjunct in smoking cessation therapy. A double‐blind randomized study controlled with placebo [Italian] [Effetti del rilascio transdermico di nicotina come terapia di supporto per lo svezzamento dal fumo di sigaretta. Uno studio randomizzato in doppio cieco con controlli trattati con placebo.]. Archivio Monaldi per le Malattie de Torace 1992;47(1‐6):17‐29. - PubMed
Dennis 2016 {published data only}
    1. Dennis PA, Kimbrel NA, Dedert EA, Beckham JC, Dennis MF, Calhoun PS. Supplemental nicotine preloading for smoking cessation in posttraumatic stress disorder: Results from a randomized controlled trial. Addictive Behaviors 2016;59:24‐29. [DOI: 10.1016/j.addbeh.2016.03.004] - DOI - PMC - PubMed
Garvey 2000 {published data only}
    1. Doherty K, Militello FS, Kinnunen T, Garvey AJ. Nicotine gum dose and weight gain after smoking cessation. Journal of Consulting and Clinical Psychology 1996;64(4):799‐807. - PubMed
    1. Ferguson SG, Shiffman S, Rohay JM, Gitchell JG, Garvey AJ. Effect of compliance with nicotine gum dosing on weight gained during a quit attempt. Addiction 2011;106(3):651‐6. - PubMed
    1. Garvey AJ, Kinnunen T, Nordstrom BL, Utman CH, Doherty K, Rosner B, et al. Effects of nicotine gum dose by level of nicotine dependence. Nicotine & Tobacco Research 2000;2(1):53‐63. - PubMed
    1. Kinnunen T, Doherty K, Militello FS, Garvey AJ. Depression and smoking cessation ‐ characteristics of depressed smokers and effects of nicotine replacement. Journal of Consulting and Clinical Psychology 1996;64(4):791‐8. - PubMed
    1. Nordstrom BL, Kinnunen T, Utman CH, Garvey AJ. Long‐term effects of nicotine gum on weight gain after smoking cessation. Nicotine & Tobacco Research 1999;1(3):259‐68. - PubMed
Glavas 2003 {published data only}
    1. Glavas D, Rumboldt Z. Smoking cessation using the transdermal nicotine system [Odvikavanje od pusenja transdermalnim nikotinskim sustavom]. Lijecnicki Vjesnik 2003;125(1‐2):8‐12. - PubMed
Goldstein 1989 {published data only}
    1. Goldstein MG, Niaura R, Follick MJ, Abrams DB. Effects of behavioral skills training and schedule of nicotine gum administration on smoking cessation. American Journal of Psychiatry 1989;146(1):56‐60. - PubMed
Hall 2009 {published data only}
    1. Barnett PG, Wong W, Jeffers A, Muñoz R, Humfleet G, Hall S. Cost‐effectiveness of extended cessation treatment for older smokers. Addiction 2014;109(2):314‐22. [DOI: 10.1111/add.12404] - DOI - PMC - PubMed
    1. Grady ES, Humfleet GL, Delucchi KL, Reus VI, Muñoz RF, Hall SM. Smoking cessation outcomes among sexual and gender minority and nonminority smokers in extended smoking treatments. Nicotine & Tobacco Research 2014;16(9):1207‐15. - PMC - PubMed
    1. Hall SM, Humfleet GL, Muñoz RF, Reus VI, Robbins JA, Prochaska JJ. Extended treatment of older cigarette smokers. Addiction 2009;104(6):1043‐52. [DOI: 10.1111/j.1360-0443.2009.02548.x] - DOI - PMC - PubMed
Hays 1999 {published data only}
    1. Hays JT, Croghan GA, Offord KP, Wolter TD, Nides MA, Davidson M. Over‐the‐counter (OTC) transdermal nicotine patch therapy. Journal of Addictive Diseases 1997;16:136.
    1. Hays JT, Croghan GA, Schroeder DR, Offord KP, Hurt RD, Wolter TD, et al. Over‐the‐counter nicotine patch therapy for smoking cessation: Results from randomized, double‐blind, placebo‐controlled and open label trials. American Journal of Public Health 1999;89(11):1701‐7. - PMC - PubMed
    1. Hays JT, Croghan IT, Offord KP, Hurt RD, Schroeder DR, Wolter TD, et al. Over the counter 22mg nicotine patch therapy for smoking cessation: results from randomized double‐blind placebo‐controlled and open label trials. Society for Research on Nicotine and Tobacco 5th Annual Meeting, 1999, San Diego (CA) 1999. - PMC - PubMed
Herrera 1995 {published data only}
    1. Herrera N, Franco R, Herrera L, Partidas A, Rolando R, Fagerström KO. Nicotine gum, 2 and 4 mg, for nicotine dependence. A double‐blind placebo‐controlled trial within a behavior modification support program. Chest 1995;108(2):447‐51. - PubMed
Hilleman 1994 {published data only}
    1. Hilleman DE, Mohiuddin SM, Delcore MG. Comparison of fixed‐dose transdermal nicotine, tapered‐dose transdermal nicotine, and buspirone in smoking cessation. Journal of Clinical Pharmacology 1994;34(3):222‐4. - PubMed
Hughes 1990 {published data only}
    1. Hughes JR, Gust SW, Keenan RM, Fenwick JW. Effect of dose on nicotine's reinforcing, withdrawal‐suppression and self‐reported effects. Journal of Pharmacology and Experimental Therapeutics 1990;252(3):1175‐83. - PubMed
Hughes 1991 {published data only}
    1. Hughes JR, Wadland WC, Fenwick JW, Lewis J, Bickel WK. Effect of cost on the self‐administration and efficacy of nicotine gum: a preliminary study. Preventive Medicine 1991;20(4):486‐96. - PubMed
Hughes 1999 {published data only}
    1. Hughes JR, Lesmes GR, Hatsukami DK, Richmond RL, Lichtenstein E, Jorenby DE, et al. Are higher doses of nicotine replacement more effective for smoking cessation?. Nicotine & Tobacco Research 1999;1(2):169‐74. - PubMed
Hughes 2018 {published data only}
    1. Hughes JR, Solomon LJ, Peasley‐Miklus CE, Callas PW, Fingar JR. Effectiveness of continuing nicotine replacement after a lapse: A randomized trial. Addictive Behaviors 2018;76:68‐81. [DOI: 10.1016/j.addbeh.2017.07.023] - DOI - PubMed
    1. NCT01807871. Treatment of Smoking Lapses and Relapses. https://clinicaltrials.gov/ct2/show/NCT01807871 (first posted March 8 2013).
Jorenby 1995 {published data only}
    1. Jorenby DE, Smith SS, Fiore MC, Hurt RD, Offord KP, Crogham IT, et al. Varying nicotine patch dose and type of smoking cessation counseling. JAMA 1995;274(17):1347‐52. - PubMed
Kalman 2006 {published data only}
    1. Kalman D, Denison H, Penk W, Peer J, Kresman D, Monti P. Early findings from a treatment study of heavy smokers in alcohol recovery. Society for Research on Nicotine and Tobacco 7th Annual Meeting 2001 03 23‐23; Seattle, Washington. 2001:61. [PO2 34]
    1. Kalman D, Kahler CW, Garvey AJ, Monti PM. High‐dose nicotine patch therapy for smokers with a history of alcohol dependence: 36‐week outcomes. Journal of Substance Abuse Treatment 2006;30(3):213‐7. - PubMed
    1. Kalman D, Kahler CW, Tirch D, Kaschub C, Penk W, Monti PM. Twelve‐week outcomes from an investigation of high‐dose nicotine patch therapy for heavy smokers with a past history of alcohol dependence. Psychology of Addictive Behaviors 2004;18(1):78‐82. - PubMed
    1. Kalman D, Tirch D, Penk W, Denison H. An investigation of predictors of nicotine abstinence in a smoking cessation treatment study of smokers with a past history of alcohol dependence. Psychology of Addictive Behaviors 2002;16(4):346‐9. - PubMed
    1. Kalman D, Tirch D, Penk W, Kaschub C. Preliminary findings from a treatment study of heavy smokers in alcohol recovery: end of treatment outcomes (PO2 38). Society for Research on Nicotine and Tobacco 8th Annual Meeting, 2002 02 20‐23; Savannah, Georgia. 2002:58.
Killen 1990 {published data only}
    1. Fortmann SP, Killen JD, Telch MJ, Newman B. Minimal contact treatment for smoking cessation. A placebo controlled trial of nicotine polacrilex and self‐directed relapse prevention: initial results of the Stanford Stop Smoking Project. JAMA 1988;260(11):1575‐80. - PubMed
    1. Killen JD, Fortmann SP, Newman B, Varady A. Evaluation of a treatment approach combining nicotine gum with self‐guided behavioral treatments for smoking relapse prevention. Journal of Consulting and Clinical Psychology 1990;58(1):85‐92. - PubMed
Killen 1999 {published data only}
    1. Killen JD, Fortmann SP, Davis L, Strausberg L, Varady A. Do heavy smokers benefit from higher dose nicotine patch therapy?. Experimental and Clinical Psychopharmacology 1999;7(3):226‐33. - PubMed
Kornitzer 1987 {published data only}
    1. Kornitzer M, Kittel F, Dramaix M, Bourdoux P. A double blind study of 2 mg versus 4 mg nicotine‐gum in an industrial setting. Journal of Psychosomatic Research 1987;31(2):171‐6. - PubMed
Kornitzer 1995 {published data only}
    1. Kornitzer M, Boutsen M, Dramaix M, Thijs J, Gustavsson G. Combined use of nicotine patch and gum in smoking cessation: a placebo‐controlled clinical trial. Preventive Medicine 1995;24(1):41‐7. - PubMed
    1. Kornitzer M, Boutsen M, Thijs J, Gustavsson G. Efficiency and safety of combined use of nicotine patches and nicotine gum in smoking cessation: a placebo controlled double‐blind trial. European Respiratory Journal 1993;6(Suppl 17):630S.
Krupski 2016 {published data only}
    1. Krupski L, Cummings MK, Hyland A, Mahoney MC, Toll BA, Carpenter MJ, et al. Cost and effectiveness of combination nicotine replacement therapy among heavy smokers contacting a quitline. Journal of Smoking Cessation 2016;11(1):50‐9. [DOI: 10.1017/jsc.2014.15] - DOI
Kupecz 1996 {published data only}
    1. Kupecz D, Prochazka A. A comparison of nicotine delivery systems in a multimodality smoking cessation program. Nurse Practitioner 1996;21(2):73, 77‐8, 81. - PubMed
Lerman 2004 {published data only}
    1. Lerman C, Jepson C, Wileyto EP, Epstein LH, Rukstalis M, Patterson F, et al. Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials. Neuropsychopharmacology 2006;31(1):231‐42. - PubMed
    1. Lerman C, Kaufmann V, Rukstalis M, Patterson F, Perkins K, Audrain McGovern J, et al. Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. Annals of Internal Medicine 2004;140(6):426‐33. - PubMed
    1. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A, et al. Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clinical Pharmacology and Therapeutics 2006;79(6):600‐8. - PubMed
    1. Lerman C, Wileyto EP, Patterson F, Rukstalis M, Audrain‐McGovern J, Restine S, et al. The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short‐term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics Journal 2004;4(3):184‐92. - PubMed
    1. Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF. Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Molecular Psychiatry 2006;11(4):400‐9. - PubMed
Moolchan 2005 {published data only}
    1. Collins CC, Epstein DH, Parzynski CS, Zimmerman D, Moolchan ET, Heishman SJ. Puffing behavior during the smoking of a single cigarette in tobacco‐dependent adolescents. Nicotine & Tobacco Research 2010;12(2):164‐7. - PMC - PubMed
    1. Franken FH, Pickworth WB, Epstein DH, Moolchan ET. Smoking rates and topography predict adolescent smoking cessation following treatment with nicotine replacement therapy. Cancer Epidemiology, Biomarkers & Prevention 2006;15(1):154‐7. - PubMed
    1. Jaszyna‐Gasior M, Schroeder JR, Thorner ED, Heishman SJ, Collins CC, Lo S, et al. Age at menarche and weight concerns in relation to smoking trajectory and dependence among adolescent girls enrolled in a smoking cessation trial. Addictive Behaviors 2009;34(1):92‐5. - PubMed
    1. Moolchan ET, Robinson ML, Ernst M, Cadet JL, Pickworth WB, Heishman SJ, et al. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics 2005;115(4):e407‐e414. - PubMed
    1. Robinson ML, Schroeder JR, Moolchan ET. Adolescent smokers screened for a nicotine replacement treatment trial: Correlates of eligibility and enrollment. Nicotine & Tobacco Research 2006;8(3):447‐54. - PubMed
Paoletti 1996 {published data only}
    1. Cosci F, Corlando A, Fornai E, Pistelli F, Paoletti P, Carrozzi L. Nicotine dependence, psychological distress and personality traits as possible predictors of smoking cessation. Results of a double‐blind study with nicotine patch. Addictive Behaviors 2009;34(1):28‐35. - PubMed
    1. Fornai E, Desideri M, Pistelli F, Carrozzi L, Puntoni R, Avino S, et al. Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch. Monaldi Archives for Chest Disease 2001;56(1):5‐10. - PubMed
    1. Paoletti P, Fornai E, Maggiorelli F, Puntoni R, Viegi G, Carrozzi L, et al. Importance of baseline cotinine plasma values in smoking cessation: results from a double blind study with nicotine patch. European Respiratory Journal 1996;9(4):643‐51. - PubMed
Piper 2009 {published data only}
    1. Asthana A, Johnson HM, Piper ME, Fiore MC, Baker TB, Stein JH. Effects of smoking intensity and cessation on inflammatory markers in a large cohort of active smokers. American Heart Journal 2010;160(3):458‐63. - PMC - PubMed
    1. Bekiroglu K, Russell MA, Lagoa CM, Lanza ST, Piper ME. Evaluating the effect of smoking cessation treatment on a complex dynamical system. Drug & Alcohol Dependence 2017;180:215‐22. [DOI: 10.1016/j.drugalcdep.2017.07.037] - DOI - PMC - PubMed
    1. Berg KM, Piper ME, Smith SS, Fiore MC, Jorenby DE. Defining and predicting short‐term alcohol use changes during a smoking cessation attempt. Addictive Behaviors 2015;48:52‐7. - PMC - PubMed
    1. Chen LS, Bloom AJ, Baker TB, Smith SS, Piper ME, Martinez M, et al. Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction 2014;109(1):128‐37. - PMC - PubMed
    1. Cook JW, Lanza ST, Chu W, Baker TB, Piper ME. Anhedonia: its dynamic relations with craving, negative affect, and treatment during a quit smoking attempt. Nicotine & Tobacco Research 2017;19(6):703‐9. [DOI: ] - PMC - PubMed
Piper 2016 {published data only}
    1. Piper ME Schlam TR, Cook JW, Smith SS, Bolt DM, Loh WY, et al. Toward precision smoking cessation treatment I: Moderator results from a factorial experiment. Drug and Alcohol Dependence 2017;171:59‐65. [DOI: 10.1016/j.drugalcdep.2016.11.025] - DOI - PMC - PubMed
    1. Piper ME, Cook JW, Schlam TR, Smith SS, Bolt DM, Collins LM, et al. Toward precision smoking cessation treatment II: Proximal effects of smoking cessation intervention components on putative mechanisms of action. Drug and Alcohol Dependence 2017;171:50‐8. [DOI: 10.1016/j.drugalcdep.2016.11.027] - DOI - PMC - PubMed
    1. Piper ME, Fiore MC, Smith SS, Fraser D, Bolt DM, Collins LM, et al. Identifying effective intervention components for smoking cessation: a factorial screening experiment. Addiction 2016;111(1):129‐41. [DOI: 10.1111/add.13162] - DOI - PMC - PubMed
Preloading Investigators 2018 {published data only}
    1. Lindson‐Hawley N, Coleman T, Docherty G, Hajek P, Lewis S, Lycett D, et al. Nicotine patch preloading for smoking cessation (the preloading trial): Study protocol for a randomized controlled trial. Trials 2014;15(1):1‐18. [DOI: 10.1186/1745-6215-15-296] - DOI - PMC - PubMed
    1. The Preloading Investigators. Effects on abstinence of nicotine patch treatment before quitting smoking: parallel, two arm, pragmatic randomised trial. BMJ 2018;361:k2164. [DOI: 10.1136/bmj.k2164] - DOI - PMC - PubMed
Puska 1995 {published data only}
    1. Puska P, Korhonen HJ, Vartiainen E, Urjanheimo EL, Gustavsson G, Westin A. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: a clinical trial in North Karelia. Tobacco Control 1995;4:231‐5.
Rey 2009 {published data only}
    1. NCT00861276. Nicotine substitute prescribed at hourly intake or ad libitum for heavy smokers willing to wuit (SUNIC). clinicaltrials.gov/ct2/show/NCT00861276 (first received 13 March 2009).
    1. Rey L, Vaucher P, Secretan F, Zellweger JP, Bodenmann P. Use of nicotine substitute prescribed at hourly plus ad libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial. Substance Abuse Treatment, Prevention, and Policy 2009;4:12. - PMC - PubMed
Rose 1994 {published data only}
    1. Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV. Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Clinical Pharmacology and Therapeutics 1994;56(1):86‐99. - PubMed
    1. Rose JE, Westman EC, Behm FM. Nicotine/mecamylamine combination treatment for smoking cessation [published erratum appears in Drug Development Research 1997;40:215]. Drug Development Research 1996;38:243‐56.
Rose 1998 {published data only}
    1. Rose JE, Behm FM, Westman EC. Nicotine‐mecamylamine treatment for smoking cessation: the role of pre‐cessation therapy. Experimental and Clinical Psychopharmacology 1998;6(3):331‐43. - PubMed
    1. Rose JE, Westman EC, Behm FM. Nicotine/mecamylamine combination treatment for smoking cessation [published erratum appears in Drug Development Research 1997;40:215]. Drug Development Research 1996;38:243‐56.
Rose 2006 {published data only}
    1. Rose JE, Behm FM, Westman EC, Kukovich P. Precessation treatment with nicotine skin patch facilitates smoking cessation. Nicotine & Tobacco Research 2006;8(1):89‐101. - PubMed
Rose 2009 {published and unpublished data}
    1. Rose JE. Nicotine preloading: The importance of a pre‐cessation reduction in smoking behavior. Psychopharmacology 2011;217(3):453‐4. - PubMed
    1. Rose JE, Herskovic JE, Behm FM, Westman EC. Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment. Nicotine & Tobacco Research 2009;11(9):1067‐75. - PubMed
Rose 2010 {published and unpublished data}
    1. Rose JE. Nicotine preloading: The importance of a pre‐cessation reduction in smoking behavior. Psychopharmacology 2011;217(3):453‐4. - PubMed
    1. Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR. Personalized smoking cessation: interactions between nicotine dose, dependence and quit‐success genotype score. Molecular Medicine 2010;16(7‐8):247‐53. - PMC - PubMed
    1. Uhl GR, Drgon T, Johnson C, Ramoni MF, Behm FM, Rose JE. Genome‐wide association for smoking cessation success in a trial of precessation nicotine replacement. Molecular Medicine 2010;16(11‐12):513‐26. - PMC - PubMed
Schlam 2016 {published data only}
    1. Schlam TR, Fiore MC, Smith SS, Fraser D, Bolt DM, Collins LM, et al. Comparative effectiveness of intervention components for producing long‐term abstinence from smoking: a factorial screening experiment. Addiction 2016;111(1):142‐55. [DOI: 10.1111/add.13153] - DOI - PMC - PubMed
Schnoll 2010a {published data only}
    1. Lerman C, Jepson C, Wileyto EP, Patterson F, Schnoll R, Mroziewicz M, et al. Genetic variation in nicotine metabolism predicts the efficacy of extended‐duration transdermal nicotine therapy. Clinical Pharmacology and Therapeutics 2010;87(5):553‐7. - PMC - PubMed
    1. Schnoll RA, Patterson F, Wileyto EP, Heitjan DF, Shields AE, Asch DA, et al. Effectiveness of extended‐duration transdermal nicotine therapy: a randomized trial. Annals of Internal Medicine 2010;152(3):144‐51. - PMC - PubMed
    1. Schnoll RA, Wileyto EP, Lerman C. Extended duration therapy with transdermal nicotine may attenuate weight gain following smoking cessation. Addictive Behaviors 2012;37(4):565‐8. - PMC - PubMed
Schnoll 2010b {published data only}
    1. Schnoll RA, Martinez E, Tatum KL, Glass M, Bernath A, Ferris D, et al. Increased self‐efficacy to quit and perceived control over withdrawal symptoms predict smoking cessation following nicotine dependence treatment. Addictive Behaviors 2011;36(1‐2):144‐7. - PMC - PubMed
    1. Schnoll RA, Martinez E, Tatum KL, Glass M, Bernath A, Ferris D, et al. Nicotine patch vs. nicotine lozenge for smoking cessation: an effectiveness trial coordinated by the Community Clinical Oncology Program. Drug and Alcohol Dependence 2010;107(2‐3):237‐43. - PMC - PubMed
Schnoll 2015 {published and unpublished data}
    1. Schnoll RA, Goelz PM, Veluz‐Wilkins A, Blazekovic S, Powers L, Leone FT, et al. Long‐term nicotine replacement therapy: a randomized clinical trial. JAMA Internal Medicine 2015;175(4):504‐11. [DOI: 10.1001/jamainternmed.2014.8313] - DOI - PMC - PubMed
Schuurmans 2004 {published data only}
    1. Schuurmans MM, Diacon AH, Biljon X, Bolliger CT. Effect of pre‐treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial. Addiction 2004;99(5):634‐40. - PubMed
    1. Schuurmans MM, Diacon AH, Biljon X, Westin A, Landfeldt B, Bolliger CT. Effect of pre‐treatment with nicotine patch on withdrawal symptoms in smokers subsequently quitting with the nicotine patch: a double‐blind randomised controlled trial. European Respiratory Society Annual Congress, Stockholm (www.ersnetsecure.org/public/prg_congres.abstract?ww_i_presentation=6711). 2002.
Smith 2009 {published data only}
    1. Smith SS, McCarthy DE, Japuntich SJ, Christiansen B, Piper ME, Jorenby DE, et al. Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Archives of Internal Medicine 2009;169(22):2148‐55. - PMC - PubMed
Smith 2013 {published data only}
    1. Smith SS, Keller PA, Kobinsky KH, Baker TB, Fraser DL, Bush T, et al. Enhancing tobacco quitline effectiveness: identifying a superior pharmacotherapy adjuvant. Nicotine & Tobacco Research 2012;15(3):718‐28. [10.1093/ntr/nts186] - PMC - PubMed
Stapleton 1995 {published data only}
    1. Russell MA, Stapleton JA, Feyerabend C, Wiseman SM, Gustavsson G, Sawe U, et al. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. BMJ 1993;306(6888):1308‐12. - PMC - PubMed
    1. Stapleton JA, Russell MA, Feyerabend C, Wiseman SM, Gustavsson G, Sawe U, et al. Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Addiction 1995;90(1):31‐42. - PubMed
TNSG 1991 {published data only}
    1. Daughton DM, Fortmann SP, Glover ED, Hatsukami DK, Heatley SA, Lichtenstein E, et al. The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post‐quit day. Preventive Medicine 1999;28(2):113‐8. - PubMed
    1. Ferguson SG, Gitchell JG, Shiffman S, Sembower MA. Prediction of abstinence at 10 weeks based on smoking status at 2 weeks during a quit attempt: secondary analysis of two parallel, 10‐week, randomized, double‐blind, placebo‐controlled clinical trials of 21‐mg nicotine patch in adult smokers. Clinical Therapeutics 2009;31(9):1957‐65. - PubMed
    1. Swan GE, Jack LM, Ward MM. Subgroups of smokers with different success rates after use of transdermal nicotine. Addiction 1997;92(2):207‐17. - PubMed
    1. Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. Six‐month results from two multicenter controlled clinical trials. Transdermal Nicotine Study Group. JAMA 1991;266(22):3133‐8. - PubMed
Tulloch 2016 {published data only}
    1. Tulloch H, Pipe A, Els C, Aitken D, Clyde M, Corran B, Reid RD. 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. Contemporary Clinical Trials 2014;38(2):304‐13. [DOI: 10.1016/j.cct.2014.05.011] - DOI - PubMed
    1. Tulloch HE, Pipe AL, Clyde MJ, Reid RD, Els C. The quit experience and concerns of smokers with psychiatric illness. American Journal of Preventive Medicine 2016;50(6):709‐18. [DOI: 10.1016/j.amepre.2015.11.006] - DOI - PubMed
    1. Tulloch HE, Pipe AL, Els C, Clyde MJ, Reid RD. Flexible, dual‐form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial. BMC Medicine 2016;14:80. [DOI: 10.1186/s12916-016-0626-2] - DOI - PMC - PubMed
Tønnesen 1988 {published data only}
    1. Tønnesen P, Fryd V, Hansen M, Helsted J, Gunnersen AB, Forchammer H, et al. Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. New England Journal of Medicine 1988;318(1):15‐8. - PubMed
Tønnesen 1996 {published data only}
    1. Tønnesen P, Mikkelsen K, Norregaard J, Jorgensen S. Recycling of hard‐core smokers with nicotine nasal spray. European Respiratory Journal 1996;9(8):1619‐23. - PubMed
Tønnesen 2000 {published data only}
    1. Tønnesen P, Mikkelsen KL. Smoking cessation with four nicotine replacement regimes in a lung clinic. European Respiratory Journal 2000;16(4):717‐22. - PubMed
Walker 2011 {published data only}
    1. Walker N, Howe C, Bullen C, Grigg M, Glover M, McRobbie H, et al. Does improved access and greater choice of nicotine replacement therapy affect smoking cessation success? Findings from a randomized controlled trial. Addiction 2011;106(6):1176‐85. - PubMed

References to studies excluded from this review

ACTRN12612001210864 {unpublished data only}
    1. ACTRN12612001210864. Can using nicotine as a long‐term substitute enhance smoking cessation over using it only as a cessation aid? [An open‐label randomised pragmatic policy trial examining effectiveness of short‐term use of Nicotine Replacement Therapy (NRT) vs short‐ or long‐term use of NRT vs short‐ or long‐term use of NRT or electronic nicotine delivery systems for smoking cessation in cigarette smokers]. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001210864 (first received 15 November 2012).
Aubin 2006 {published data only}
    1. Aubin HJ, Luthringer R, Demazieres A, Dupont C, Lagrue G. Comparison of the effects of a 24‐hour nicotine patch and a 16‐hour nicotine patch on smoking urges and sleep. Nicotine & Tobacco Research 2006;8(2):193‐201. - PubMed
Berlin 2011 {published data only}
    1. Berlin I, Jacob N, Coudert M, Perriot J, Schultz L, Rodon N. Adjustment of nicotine replacement therapies according to saliva cotinine concentration: the ADONIS* trial‐a randomized study in smokers with medical comorbidities. Addiction 2011;106(4):833‐43. - PubMed
    1. Berlin I, Singleton EG, Heishman SJ. Validity of the 12‐item French version of the Tobacco Craving Questionnaire in treatment‐seeking smokers. Nicotine & Tobacco Research 2010;12(5):500‐7. - PMC - PubMed
Berlin 2012 {published data only}
    1. Berlin I, Hunneyball IM, Greiling D, Jones SP, Fuder H, Stahl HD. A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch. Psychopharmacology 2012;223(1):89‐98. - PubMed
Carpenter 2011 {published data only}
    1. Carpenter MJ, Alberg AJ, Gray KM, Saladin ME. Motivating the unmotivated for health behavior change: a randomized trial of cessation induction for smokers. Clinical Trials 2010;7(2):157‐66. - PMC - PubMed
    1. Carpenter MJ, Hughes JR, Gray KM, Wahlquist AE, Saladin ME, Alberg AJ. Nicotine therapy sampling to induce quit attempts among smokers unmotivated to quit: a randomized clinical trial. Archives of Internal Medicine 2011;171(21):1901‐7. - PMC - PubMed
Chan 2010 {published data only}
    1. Chan SS, Leung DY, Abdullah AS, Lo SS, Yip AW, Kok WM, et al. Smoking‐cessation and adherence intervention among Chinese patients with erectile dysfunction. American Journal of Preventive Medicine 2010;39(3):251‐8. - PubMed
Dey 1999 {published data only}
    1. Dey P, Foy R, Woodman M, Fullard B, Gibbs A. Should smoking cessation cost a packet? A pilot randomized controlled trial of the cost‐effectiveness of distributing nicotine therapy free of charge. British Journal of General Practice 1999;49(439):127‐8. - PMC - PubMed
Etter 2009 {published data only}
    1. Etter JF, Huguelet P, Perneger TV, Cornuz J. Nicotine gum treatment before smoking cessation: a randomized trial. Archives of Internal Medicine 2009;169(11):1028‐34. - PubMed
Fagerström 1993 {published data only}
    1. Fagerström KO, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology (Berl) 1993;111(3):271‐7. - PubMed
Fagerström 1997 {published data only}
    1. Fagerström KO, Tejding R, Westin A, Lunell E. Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker?. Tobacco Control 1997;6(4):311‐6. - PMC - PubMed
Fagerström 2000 {published data only}
    1. Fagerström KO, Hughes JR, Rasmussen T, Callas PW. Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit. Tobacco Control 2000;9(3):327‐33. - PMC - PubMed
Ferguson 2015 {published data only}
    1. Ferguson SG, Walters JA, Lu W, Wells GP, Schuz N. Examination of the mechanism of action of two pre‐quit pharmacotherapies for smoking cessation. BMC Public Health 2015;15(1):1268‐73. - PMC - PubMed
Finland unpublished {unpublished data only}
    1. Anon. Combination NRT; Improving efficacy in smoking cessation. McNeil Consumer Healthcare booklet, 2007. Short term outcomes reported on p17.
Garvey 2006 {unpublished data only}
    1. Garvey AJ, Hoskinson RA, Wadler BM, Kinnunen T, Sachs DP. Individualising nicotine patch dose to match smokers' usual nicotine intake levels (PA9‐4). Society for Research on Nicotine and Tobacco 12th Annual Meeting 2006 02 15‐18, Orlando, Florida. 2006:32.
    1. Mustonen TK, Spencer SM, Hoskinson RA, Sachs DPL, Garvey AJ. The influence of gender, race, and menthol content on tobacco exposure measures. Nicotine & Tobacco Research 2005;7(4):581‐90. - PubMed
Hajek 1999 {published data only}
    1. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Archives of Internal Medicine 1999;159(17):2033‐8. - PubMed
    1. West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl) 2000;149(3):198‐202. - PubMed
Haustein 2003 {published data only}
    1. Haustein KO, Batra A, Landfeldt B, Westin A. The effect of short‐term or long‐term reduction on smoking cessation; results from a placebo controlled smoking reduction study with the nicotine gum. Nicotine & Tobacco Research 2003;5:278.
    1. Pfizer. Summary of Clinical Efficacy. Application for licensing of Nicorette Inhalator/Gum for smoking reduction leading to cessation. Company data NICORE‐1013‐273‐SU.
Hollands 2013 {published data only}
    1. Hollands GJ, Sutton S, McDermott MS, Marteau TM, Aveyard P. Adherence to and consumption of nicotine replacement therapy and the relationship with abstinence within a smoking cessation trial in primary care. Nicotine & Tobacco Research 2013;15(9):1537‐44. - PMC - PubMed
Hughes 1989b {published data only}
    1. Hughes JR, Gulliver SB, Amori G, Mireault GC, Fenwick JF. Effect of instructions and nicotine on smoking cessation, withdrawal symptoms and self‐administration of nicotine gum. Psychopharmacology (Berl) 1989;99(4):486‐91. - PubMed
Hughes 2010 {published data only}
    1. Hughes JR, Solomon LJ, Livingston AE, Callas PW, Peters EN. A randomized, controlled trial of NRT‐aided gradual vs. abrupt cessation in smokers actively trying to quit. Drug & Alcohol Dependence 2010;111(1‐2):105‐13. [NCT00297492] - PMC - PubMed
Jibrail 2010 {published data only}
    1. Jibrail JJ, Cortas NK, Sarieddine DS, Kanj NA, Zaatari GS, Daher RT. Impact of nicotine metabolite monitoring on the efficacy of smoke cessation and usefulness of sequential CRP measurements. American Journal of Respiratory Critical Care Medicine 2010;181:A2652.
Kozak 1995 {published data only}
    1. Kozak J, Fagerström KO, Sawe U. High‐dose treatment with the nicotine patch. International Journal of Smoking Cessation 1995;4(2):26‐8.
Kras 2010 {published data only}
    1. Kras M, Stough C, Scholey A, Kure C, Camfield D. Hypericum perforatum, nicotine patches and combination hypericum perforatum/nicotine patches for smoking cessation. European Neuropsychopharmacology 2010;20:S608‐9.
Landfeldt 1998 {unpublished data only}
    1. Landfeldt B, Kruse E, Westin A, Mattson K, Lojander J. Nicotine replacement treatment in heavy smokers: nicotine nasal spray combined with nicotine patch in a double‐blind controlled study. European Respiratory Journal 1998;12(Suppl 28):154S.
Leischow 1999 {published data only}
    1. Leischow SJ, Muramoto ML, Cook GN, Merikle EP, Castellini SM, Otte PS. OTC nicotine patch: effectiveness alone and with brief physician intervention. American Journal of Health Behavior 1999;23:61‐9.
Leischow 2004 {published data only}
    1. Leischow SJ, Ranger‐Moore J, Muramoto ML, Matthews E. Effectiveness of the nicotine inhaler for smoking cessation in an OTC setting. American Journal of Health Behavior 2004;28(4):291‐301. - PubMed
    1. Leischow SJ, Ranger‐Moore J, Muramoto ML, Matthews E. The safety and effectiveness of the nicotine inhaler for smoking cessation in an over‐the‐counter setting (POS4‐78). Society for Research on Nicotine and Tobacco 9th Annual Meeting, 2003 New Orleans, LA. 2003:100.
Lu 2017 {published data only}
    1. Lu W, Chappell K, Walters JA, Jacobson GA, Patel R, Schuz N, et al. The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre‐quit pharmacotherapies. Psychopharmacology 2017;234(Suppl 2):1‐8. - PubMed
Marsh 2005 {published data only}
    1. Marsh HS, Dresler CM, Choi JH, Targett DA, Gamble ML, Strahs KR. Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: A 12‐week, randomized, open‐label study. Clinical Therapeutics 2005;27(10):1571‐87. - PubMed
McRobbie 2010 {published data only}
    1. McRobbie H, Thornley S, Bullen C, Lin RB, Senior H, Laugesen M, et al. A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfaction. Addiction 2010;105(7):1290‐8. - PubMed
Minneker 1989 {published data only}
    1. Minneker E, Buchkremer G, Block M. The effect of different dosages of a transdermal nicotine substitution system on the success rate of smoking cessation therapy. Methods and Findings in Experimental and Clinical Pharmacology 1989;11(3):219‐22. - PubMed
NCT00985985 {unpublished data only}
    1. NCT00985985. A multi‐center, randomized, double‐blind, parallel, placebo‐controlled clinical study to evaluate efficacy and safety of nicotine mint lozenge (2mg and 4mg) in smoking cessation. www.gsk‐clinicalstudyregister.com/study/CHN‐Nicotine%20Mint%20Lozenge‐002#rs (first received July 16 2009).
    1. NCT00985985. Efficacy and safety study of nicotine mint lozenge (2mg and 4mg) in smoking cessation. clinicaltrials.gov/ct2/show/NCT00985985 (first received 29 September 2009).
NCT01592695 {unpublished data only}
    1. NCT01592695. Tailored tobacco cessation program for rural vVeterans with comorbid depression, alcoholism or obesity. clinicaltrials.gov/show/NCT01592695 (first received 11 April 2012).
NCT01892813 {unpublished data only}
    1. NCT01892813. Dissemination of a tailored tobacco quitline for rural veteran smokers. clinicaltrials.gov/ct2/show/NCT01892813 (first received 1 July 2013).
NCT02147132 {unpublished data only}
    1. NCT02147132. Pilot study of nicotine nasal spray and varenicline on smoking in methadone‐maintained patients. clinicaltrials.gov/ct2/show/NCT02147132 (first received 19 May 2014).
NCT02271919 {unpublished data only}
    1. NCT02271919. Varenicline and combined nicotine replacement therapy (NRT) for smoking cessation. clinicaltrials.gov/ct2/show/NCT02271919 (first received 17 October 2014).
Oncken 2009 {published data only}
    1. Oncken C, Campbell W, Chan G, Hatsukami D, Kranzler HR. Effects of nicotine patch or nasal spray on nicotine and cotinine concentrations in pregnant smokers. Journal of Maternal‐Fetal & Neonatal Medicine 2009;22(9):751‐8. - PMC - PubMed
Pomerleau 2003 {published data only}
    1. Lerman C, Audrain J, Patterson F, Kaufmann V, Rukstalis M, Wileyto EP, et al. Differential response to nicotine replacement therapies in obese and non‐obese women (PA2‐6). Society for Research on Nicotine and Tobacco 9th Annual Meeting, 2003 Orleans, LA. 2003.
    1. Pomerleau OF, Pomerleau CS, Marks JL, Snedecor SM, Mehringer AM, Namenek‐Brouwer RJ, et al. Prolonged nicotine patch use in quitters with past abstinence‐induced depressed mood. Journal of Substance Abuse Treatment 2003;24(1):13‐8. - PubMed
Sachs 1995 {published data only}
    1. Sachs DP. Effectiveness of the 4‐mg dose of nicotine polacrilex for the initial treatment of high‐dependent smokers. Archives of Internal Medicine 1995;155(18):1973‐80. - PubMed
Schneider 2004 {published data only}
    1. Schneider NG, Olmstead RE, Nides M, Mody FV, Otte Colquette P, Doan K, et al. Comparative testing of 5 nicotine systems: initial use and preferences. Amercian Journal of Health Behavior 2004;28(1):72‐86. - PubMed
Schneider 2008 {published data only}
    1. Schneider NG, Cortner C, Gould JL, Koury MA, Olmstead RE. Comparison of craving and withdrawal among four combination nicotine treatments. Human Psychopharmacology 2008;23(6):513‐7. - PubMed
Shahab 2011 {published data only}
    1. Shahab L, McEwen A, West R. Acceptability and effectiveness for withdrawal symptom relief of a novel oral nicotine delivery device: a randomised crossover trial. Psychopharmacology 2011;216(2):187‐96. - PubMed
Shiffman 2000a {published data only}
    1. Shiffman S, Khayrallah M, Nowak R. Efficacy of the nicotine patch for relief of craving and withdrawal 7‐10 weeks after cessation. Nicotine & Tobacco Research 2000;2(4):371‐8. - PubMed
Shiffman 2000b {published data only}
    1. Shiffman S, Elash CA, Paton SM, Gwaltney CJ, Paty JA, Clark DB, et al. Comparative efficacy of 24‐hour and 16‐hour transdermal nicotine patches for relief of morning craving. Addiction 2000;95(8):1185‐95. - PubMed
Shiffman 2002 {published data only}
    1. Shiffman S, Rolf CN, Hellebusch SJ, Gorsline J, Gorodetzky CW, Chiang YK, et al. Real‐world efficacy of prescription and over‐the‐counter nicotine replacement therapy. Addiction 2002;97(5):505‐16. - PubMed
Sutherland 1999 {published data only}
    1. Anon. Combination NRT; Improving efficacy in smoking cessation. McNeil Consumer Healthcare booklet. Short term outcomes reported on p18.
    1. Sutherland G. A placebo‐controlled double‐blind combination trial of nicotine spray and patch. Nicotine & Tobacco Research 1999;1:186.
Tundulawessa 2010 {published data only}
    1. Tundulawessa Y, Yongchaiyud P, Chutrthong W, Tundulawessa K. The bioequivalent and effect of nicotine formulation gum on smoking cessation. Journal of the Medical Association of Thailand 2010;93(5):574‐9. - PubMed
Vikhireva 2003 {published data only}
    1. Vikhireva O, Shalnova S, Deev A. Nicotine replacement therapy in Russia: old wine in new skins? Randomized parallel study of nicotine gum/inhaler in smoking cessation/reduction. Society for Research on Nicotine and Tobacco. Fifth European Conference. 2003 11 20‐22, Padua, Italy. 2003.
    1. Vikhireva O, Shalnova S, Deev A, Levshin V, Radkevich N, Kalinina A. NRT‐assisted cessation in Russia: individual and population level benefits. Society for Research on Nicotine and Tobacco 11th Annual Meeting, 2005 03 20‐23; Prague, Czech Republic. 2005.
Williams 2007 {published and unpublished data}
    1. Williams JM, Gandhi KK, Foulds J, Steinberg M, Lou S, Masumova F, et al. No advantage for high dose compared to regular dose nicotine patch on short‐term abstinence rates in schizophrenia (PA2‐3). Society for Research on Nicotine and Tobacco 13th Annual Meeting; 2007 02 21‐24; Austin, Texas. 2007.

References to ongoing studies

NCT01622998 {unpublished data only}
    1. Leblanc A, Reid R, Mark A, Tulloch H, Aitken D, Mullen K, et al. STEP‐ing up smoking cessation: weight‐related concern of participants who want to quit smoking. Obesity Facts 2017;10:207.
    1. NCT01622998. Self‐directed titrated transdermal nicotine patch versus standard treatment for smoking cessation (STEP). clinicaltrials.gov/ct2/show/NCT01622998 (first received 19 June 2012.

Additional references

BNF 2018
    1. Joint Formulary Committee. British National Formulary. 76. London: BMJ Group and Pharmaceutical Press, 2018.
Cahill 2013
    1. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta‐analysis. Cochrane Database of Systematic Reviews 2013, Issue 5. [DOI: 10.1002/14651858.CD009329.pub2] - DOI - PMC - PubMed
Cahill 2016
    1. Cahill K, Lindson‐Hawley N, Thomas KH, Fanshawe TR, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD006103.pub7] - DOI - PMC - PubMed
Carson 2012
    1. Carson KV, Verbiest ME, Crone MR, Brinn MP, Esterman AJ, Assendelft WJ, et al. Training health professionals in smoking cessation. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD000214.pub2] - DOI - PMC - PubMed
CDC 2017
    1. Centers for Disease Control and Prevention. Quitting Smoking Among Adults—United States, 2000–2015. Morbidity and Mortality Weekly Report 2017;65(52):1457‐64. - PubMed
Coleman 2015
    1. Coleman T, Chamberlain C, Davey M, Cooper SE, Leonardi‐Bee J. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database of Systematic Reviews 2015, Issue 12. [DOI: 10.1002/14651858.CD010078.pub2] - DOI - PubMed
Deeks 2017
    1. Deeks J, Higgins JP, Altman DG, (editors) on behalf of the Cochrane Statistical Methods Group. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Fagerström 2012
    1. Fagerström K. Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence. Nicotine & Tobacco Research 2012;14(1):75‐8. [DOI: ] - PubMed
Fanshawe 2017
    1. Fanshawe TR, Halliwell W, Lindson N, Aveyard P, Livingstone‐Banks J, Hartmann‐Boyce. Tobacco cessation interventions for young people. Cochrane Database of Systematic Reviews 2017, Issue 11. [DOI: 10.1002/14651858.CD003289.pub6] - DOI - PMC - PubMed
Fiore 1992
    1. Fiore MC, Jorenby DE, Baker TB, Kenford SL. Tobacco dependence and the nicotine patch. Clinical guidelines for effective use. JAMA 1992;268(19):2687‐94. - PubMed
Fiore 2008
    1. Fiore MC, Jaén CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service, May 2008.
GBD 2015 Risk Factors Collaborators 2016
    1. GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388(10053):1659‐724. [DOI: 10.1016/S0140-6736(16)31679-8] - DOI - PMC - PubMed
Hartmann‐Boyce 2016
    1. Hartmann‐Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews 2016, Issue 9. [DOI: 10.1002/14651858.CD010216.pub3] - DOI - PMC - PubMed
Hartmann‐Boyce 2018
    1. Hartmann‐Boyce J, Chepkin SC, Ye W, Bullen C, Lancaster T. Nicotine replacement therapy versus control for smoking cessation. Cochrane Database of Systematic Reviews 2018, Issue 5. [DOI: 10.1002/14651858.CD000146.pub5] - DOI - PMC - PubMed
Henningfield 2005
    1. Henningfield JE, Fant RV, Buchhalter AR, Stitzer ML. Pharmacotherapy for nicotine dependence. CA Cancer Journal for Clinicians 2005;55(5):281‐99. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analysis. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Hughes 2014
    1. Hughes JR, Stead LF, Hartmann‐Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD000031.pub4] - DOI - PMC - PubMed
Italy ISS 2004
    1. Osservatorio Fumo, Alcol e Droga. Linee Guida Cliniche per Promuovere la Cessazione dell’Abitudine al Fumo. Rome: Istituto Superiore di Sanita, 2004.
Jha 2011
    1. Jha P. Avoidable deaths from smoking: a global perspective. Public Health Reviews 2011;33(2):569‐600.
Le Foll 2005
    1. Foll B, Melihan‐Cheinin P, Rostoker G, Lagrue G. Smoking cessation guidelines: evidence‐based recommendations of the French Health Products Safety Agency. European Psychiatry 2005;20(5‐6):431‐41. - PubMed
Lindson‐Hawley 2016
    1. Lindson‐Hawley N, Hartmann‐Boyce J, Fanshawe TR, Begh R, Farley A, Lancaster T. Interventions to reduce harm from continued tobacco use. Cochrane Database of Systematic Reviews 2016, Issue 10. [DOI: 10.1002/14651858.CD005231.pub3] - DOI - PMC - PubMed
McNeill 2017
    1. McNeill A, Robson D. A man before his time: Russell's insights into nicotine, smoking, treatment and curbing the smoking problem. Addiction 2017;113(4):759‐63. [DOI: 10.1111/add.14043] - DOI - PubMed
NICE 2018
    1. National Institute for Health and Care Excellence. Stop smoking interventions and services (NG92). www.nice.org.uk/guidance/ng92/resources/stop‐smoking‐interventions‐and‐s... 2018.
NZ MoH 2007
    1. New Zealand Ministry of Health. New Zealand Smoking Cessation Guidelines. Treatment%20Guidelines_New%20Zealand%20treatment%20guidelines%20in%20English%202007%20(1).pdf 2007 (accessed 3 April 2019).
West 2000
    1. West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Health Education Authority. Thorax 2000;55(12):987‐99. - PMC - PubMed
West 2001
    1. West R, .Shiffman S. Effect of oral nicotine dosing forms on cigarette withdrawal symptoms and craving: a systematic review. Psychopharmacology Berl 2001;155(2):115‐22. - PubMed
West 2005
    1. 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. [DOI: 10.1111/j.1360-0443.2004.00995.x] - DOI - PubMed
Woolacott 2002
    1. Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, et al. The clinical effectiveness and cost‐effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Health Technology Assessment 2002;6(16):1‐245. - PubMed
Zwar 2011
    1. Zwar N, Borland R, Peters M, Litt J, Bell J, Caldwell B, et al. Supporting Smoking Cessation: A Guide for Health Professionals. Melbourne: The Royal Australian College of General Practitioners, 2011.

References to other published versions of this review

Silagy 1994a
    1. Silagy C, Mant D, Fowler G, Lodge M. Meta‐analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994;343:139‐42. - PubMed
Silagy 1994b
    1. Silagy C, Mant D, Fowler G, Lancaster T. The effectiveness of nicotine replacement therapies in smoking cessation. Online Journal of Current Clinical Trials 1994;Doc No:113. - PubMed
Silagy 1996
    1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 1996, Issue 2. - PubMed
Silagy 2001
    1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2001, Issue 3. [DOI: 10.1002/14651858.CD000146] - DOI - PubMed
Silagy 2002
    1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD000146] - DOI - PubMed
Silagy 2004
    1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858.CD000146] - DOI - PubMed
Stead 2008
    1. Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD000146.pub3] - DOI - PubMed
Stead 2012
    1. Stead LF, Perera R, Bullen C, Mant D, Hartmann‐Boyce J, Cahill K, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD000146.pub4] - DOI - PubMed

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