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A Systematic Review Investigating the Impact of Modified Varenicline Regimens on Smoking Cessation

Published online by Cambridge University Press:  07 March 2017

Aaron D. Drovandi*
Affiliation:
College of Medicine and Dentistry, James Cook University, Townsville, Australia
Peta-Ann Teague
Affiliation:
College of Medicine and Dentistry, James Cook University, Townsville, Australia
Beverley D. Glass
Affiliation:
College of Medicine and Dentistry, James Cook University, Townsville, Australia
Bunmi Malau-Aduli
Affiliation:
College of Medicine and Dentistry, James Cook University, Townsville, Australia
*
Address for correspondence: Aaron Drovandi (MPharmPH), Building 047, Pharmacy, 1 James Cook Drive, James Cook University, Townsville, QLD, Australia, 4814. Email: [email protected]

Abstract

Introduction: The efficacy of varenicline as a smoking cessation aid is affected by commonly-occurring issues, such as intolerable adverse events, cravings and withdrawal symptoms, and poor medication adherence. Improvement in quit rates may be achieved through tailoring doses relative to individual smokers’ behaviours, and previous experiences with smoking cessation medications.

Aims: The aim of this review is to evaluate smoking cessation outcomes from published randomised controlled trials that have attempted to improve the efficacy and tolerability of varenicline through modifying its dosage regimen compared to placebo.

Methods: A systematic search of the literature up to June 2016 was conducted to identify randomised controlled trials, where varenicline was administered in a regimen not consistent with the current clinical guidelines. Outcome measures evaluated included continuous abstinence rates, changes in cravings, withdrawal symptoms, smoking behaviours, adverse event rates, and premature therapy discontinuations.

Results: Ten randomised controlled trials, encompassing four different modifications to standard varenicline therapy, matched the eligibility criteria. Modifications such as the extended duration of therapy and the use of a flexible quit date were effective compared to placebo and have been implemented into some clinical guidelines, whereas other modifications do not appear to produce any benefit for smokers, or require further research to ascertain their suitability for clinical practice.

Conclusions: Some varenicline therapy modifications may lead to improvements in efficacy and tolerability. Further research on the effect of modifications such as daily doses higher than 2mg, tapering doses, and the use of extended pre-quit varenicline may advance varenicline therapy outcomes.

Type
Review Article
Copyright
Copyright © The Author(s) 2017 

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References

Blaschke, T. F., Osterberg, L., Vrijens, B., & Urquhart, J. (2012). Adherence to medications: Insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annual Review of Pharmacology and Toxicology, 52, 275301.Google Scholar
Cahill, K., Stevens, S., Perera, R., & Lancaster, T. (2013). Pharmacological interventions for smoking cessation: An overview and network meta-analysis. Cochrane Database of Systematic Reviews, 5, CD009329.Google Scholar
Catz, S. L., Jack, L. M., McClure, J. B., Javitz, H. S., Deprey, M., Zbikowski, S. M. et al. (2011). Adherence to varenicline in the COMPASS smoking cessation intervention trial. Nicotine and Tobacco Research, 13 (5), 361368.Google Scholar
Coe, J. W., Brooks, P. R., Vetelino, M. G., Wirtz, M. C., Arnold, E. P., Huang, J. et al. (2005). Varenicline: An alpha4beta2 nAChR nicotinic receptor partial agonist for smoking cessation. Journal of Medicinal Chemistry, 48, 34743477.CrossRefGoogle ScholarPubMed
Drovandi, A. D., Chen, C. C., & Glass, B. D. (2016). Adverse effects cause varenicline discontinuation: A meta-analysis. Current Drug Safety, 11, 7885.Google Scholar
Fiore, M. C., Jaen, C. R., Baker, T., Bailey, W. C., Benowitz, N. L., Curry, S. J. et al. (2008). Treating tobacco use and dependence: 2008 update. Rockville, MD: US Department of Health and Human Services.Google Scholar
Gonzales, D., Rennard, S. I., Nides, M., Oncken, C., Salomon, A., Billing, C. B. et al. (2006). Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs Sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. Journal of the American Medical Association, 296 (1), 4755.Google Scholar
Hajek, P., McRobbie, H. J., Myers, K. E., Stapleton, J., & Dhangi, A. (2011). Use of varenicline for 4 weeks before quitting smoking: Decrease in ad lib smoking and increase in smoking cessation rates. Archives of Internal Medicine, 171 (8), 770777.Google Scholar
Hajek, P., McRobbie, H., Smith, K. M., Phillips, A., Cornwall, D., & Dhanji, A. (2015). Increasing varenicline dose in smokers who do not respond to the standard dosage: A randomized clinical trial. JAMA Internal Medicine, 175 (2), 266271.Google Scholar
Hajek, P., Stead, L. F., West, R., Jarvis, M., Hartmann-Boyce, J., & Lancaster, T. (2013). Relapse prevention interventions for smoking cessation (Review). Cochrane Database of Systematic Reviews, 8, CD003999.Google Scholar
Hawk, L. W., Ashare, R. L., Lohnes, S. F., Schlienz, M. A., Rhodes, J. D., Tiffany, S. T. et al. (2012). The effects of extended pre-quit varenicline treatment on smoking behaviour and short-term abstinence: A randomized clinical trial. Clinical Pharmacology and Therapeutics, 91 (2), 172180.Google Scholar
Haynes, R. B., Ackloo, E., Sahota, N., McDonald, H. P., & Yao, X. (2008). Interventions for enhancing medication adherence (Review). Cochrane Database of Systematic Reviews, 2, CD000011.Google Scholar
Hughes, J. R., Solomon, L. J., Livingston, A. E., Callas, P. W., & Peters, E. N. (2010). A randomized, controlled trial of NRT-aided gradual vs. abrupt cessation in smokers actively trying to quit. Drug and Alcohol Dependence, 111, 105113.CrossRefGoogle ScholarPubMed
Jadad, A. R., Moore, A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J. et al. (1996). Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials, 17 (1), 112.Google Scholar
Jorenby, D. E., Hays, J. T., Rigotti, N. A., Azoulay, S., Watsky, E. J., Williams, K. E. et al. (2006). Efficacy of Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs Placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. Journal of the American Medical Association, 291 (1), 5663.Google Scholar
Krall, E. A., Garvey, A. J., & Garcia, E. I. (2002). Smoking relapse after 2 years of abstinence: Findings from the VA normative aging study. Nicotine and Tobacco Research, 4 (1), 95100.Google Scholar
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLOS Medicine, 6, e1000097.Google Scholar
Nakamura, M., Oshima, A., Fujimoto, Y., Maruyama, N., Ishibasi, T., & Reeves, K. R. (2007). Efficacy and tolerability of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clinical Therapeutics, 29 (6), 10401056.Google Scholar
Niaura, R., Hays, J. T., Jorenby, D. E., Leone, F. T., Pappas, J. E., Reeves, K. R. et al. (2008). The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: A randomized controlled trial. Current Medical Research and Opinion, 24 (7), 19311941.Google Scholar
Nides, M., Oncken, C., Gonzales, D., Rennard, S., Watsky, E. J., Anziano, R. et al. (2006). Smoking cessation with varenicline, a selective α4β2 nicotinic receptor partial agonist. Archives of Internal Medicine, 166, 15611568.Google Scholar
Oncken, C., Gonzales, D., Nides, M., Rennard, S., Watsky, E., Billing, C. B. et al. (2006). Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Archives of Internal Medicine, 166, 15711577.Google Scholar
Rennard, S. I., Hughes, J., Cinciripini, P. M., Kralikova, E., Raupach, T., Arteaga, C. et al. (2012). A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Nicotine and Tobacco Research, 14 (3), 343350.Google Scholar
Rigotti, N. A., Pipe, A. L., Benowitz, N. L., Arteaga, C., Garza, D., & Tonstad, S. (2010). Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: A randomized trial. Circulation, 121, 221229.Google Scholar
Shiffman, S., Ferguson, S. G., & Strahs, K. R. (2009). Quitting by gradual smoking reduction using nicotine gum: A randomized controlled trial. American Journal of Preventive Medicine, 36, 96104.Google Scholar
Tashkin, D. P., Rennard, S., Hays, J. T., Ma, W., Lawrence, D., & Lee, T. C. (2011). Effects of varenicline on smoking cessation in patients with mild to moderate COPD. Chest, 139 (3), 591599.Google Scholar
Tonstad, S., Tǿnnesen, P., Hajek, P., Williams, K. E., Billing, C. B., & Reeves, K. R. (2006). Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. Journal of the American Medical Association, 296 (1), 6471.Google Scholar
Tsai, S., Cho, H., Cheng, S., Kim, C. H., Hsueh, K. C., Billing, C. B. Jr. et al. (2007). A randomized, placebo-controlled trial of varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clinical Therapeutics 29 (6), 10271039.Google Scholar
Williams, K. E., Reeves, K. R., Billing, C. B. Jr., Pennington, A. M., & Gong, J. (2007). A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Current Medical Research and Opinion, 23 (4), 793801.Google Scholar