Nicotine Replacement Therapy (NRT)
A variety of formulations of nicotine replacement therapies (NRTs) now exist, including the transdermal nicotine patch, nicotine spray, nicotine gum, and nicotine lozenges. Because nicotine is the main addictive ingredient in tobacco, the rationale for NRT is that stable low levels of nicotine will prevent withdrawal symptoms—which often drive continued tobacco use—and help keep people motivated to quit. Research shows that combining the patch with another replacement therapy is more effective than a single therapy alone.
Bupropion was originally marketed as an antidepressant (Wellbutrin). It produces mild stimulant effects by blocking the reuptake of certain neurotransmitters, especially norepinephrine and dopamine. A serendipitous observation among depressed patients was that the medication was also effective in suppressing tobacco craving, helping them quit smoking without also gaining weight. Although bupropion’s exact mechanisms of action in facilitating smoking cessation are unclear, it has FDA approval as a smoking cessation treatment.
Varenicline is the most recently FDA-approved medication for smoking cessation. It acts on a subset of nicotinic receptors in the brain thought to be involved in the rewarding effects of nicotine. Varenicline acts as a partial agonist/antagonist at these receptors—this means that it midly stimulates the nicotine receptor but not sufficiently to trigger the release of dopamine, which is important for the rewarding effects of nicotine. As an antagonist, varenicline also blocks the ability of nicotine to activate dopamine, interfering with the reinforcing effects of smoking, thereby reducing cravings and supporting abstinence from smoking.
Combined With Behavioral Treatment
Each of the above pharmacotherapies is recommended for use in combination with behavioral interventions, including group and individual therapies, as well as telephone quitlines. Behavioral approaches complement most tobacco addiction treatment programs. They can amplify the effects of medications by teaching people how to manage stress, recognize and avoid high-risk situations for smoking relapse, and develop alternative coping strategies (e.g., cigarette refusal skills, assertiveness, and time management skills) that they can practice in treatment, social, and work settings. Combined treatment is urged because behavioral and pharmacological treatments are thought to operate by different yet complementary mechanisms that can have additive effects.
Alterman, A.I.; Gariti, P.; and Mulvaney, F. Short- and long-term smoking cessation for three levels of intensity of behavioral treatment. Psychology of Addictive Behaviors 15:261-264, 2001.
Hall, S.M.; Humfleet, G.L.; Muñoz, R.F.; V.I; Prochaska, J.J.; and Robbins, J.A. Using extended cognitive behavioral treatment and medication to treat dependent smokers. American Journal of Public Health 101:2349– 2356, 2011.
Jorenby, D.E.; Hays, J.T.; Rigotti, N.A.; Azoulay, S.; Watsky, E.J.; Williams, K.E.; Billing, C.B.; Gong, J.; and Reeves, K.R. Varenicline Phase 3 Study Group. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist vs. placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. The Journal of the American Medical Association 296(1):56–63, 2006.
King, D.P.; Paciqa, S.; Pickering, E.; Benowitz, N.L.; Bierut, L.J.; Conti, D.V.; Kaprio, J.; Lerman, C.; and Park, P.W. Smoking cessation pharmacogenetics: Analysis of varenicline and bupropion in placebo-controlled clinical trials. Neuropsychopharmacology 37:641–650, 2012.
Raupach, T.; and van Schayck, C.P. Pharmacotherapy for smoking cessation: Current advances and research topics. CNS Drugs 25:371–382, 2011.
Shah, S.D.; Wilken, L.A.; Winkler, S.R.; and Lin, S.J. Systematic review and meta-analysis of combination therapy for smoking cessation. Journal of the American Pharmaceutical Association 48(5):659–665, 2008.
Smith, S.S; McCarthy, D.E.; Japuntich S.J.; Christiansen, B.; Piper, M.E.; Jorenby, D.E.; Fraser, D.L.; Fiore, M.C.; Baker, T.B.; and Jackson, T.C. Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Archives of Internal Medicine 169:2148–2155, 2009.
Stitzer, M. Combined behavioral and pharmacological treatments for smoking cessation. Nicotine & Tobacco Research 1:S181–S187, 1999.