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Long-term pharmacotherapy has been suggested as a potential aid to smoking cessation or harm reduction. Nicotine, bupropion and varenicline taken over long periods are likely to be much safer than cigarette smoking. However the efficacy of long-term medication use to aid cessation or reduce harm has not yet been demonstrated.



When applied to tobacco use, harm reduction usually refers to either use of safer tobacco products (see other key findings) or strategies to decrease tobacco intake among ongoing users (discussed herein) (Anderson & Hughes, 2000; IOM report, 2001; Royal College of Physicians, 2008). Harm reduction is of interest because it might be helpful for the 85% of smokers not ready to quit at any given time.

Will reduction improve health? There is a strong dose-response relationship of smoking and disease (Surgeon General's report, 2010), and some tobacco users can decrease their intake significantly (>50%) and maintain this over time (Hughes & Carpenter, 2005). On the other hand, smokers unconsciously compensate for reductions by smoking more intensely (Hatsukami et al., 2006), plus small reductions in smoking may not result in any meaningful health gains (Joseph et al., 2008; Tverdal & Bjartveit, 2006).  Also, smoking even a few cigarettes per day can be associated with significant risk (Bjartveit & Tverdal, 2005). Since documentation of health effects takes several years, scientists are currently investigating whether reduction improves known risk factors (e.g. inflammatory biomarkers or HDL cholesterol levels); however, whether these are adequate markers for disease risk is unclear (WHO Study group, 2007).

Several nicotine replacement therapies (NRTs) and bupropion appear to assist in reduction. Although the NRT and bupropion studies suggest decreases in toxin exposure despite some compensation, only a few studies have been published (Stead & Lancaster, 2007). In addition, epidemiological studies comparing reducers vs. non reducers have not shown a significant reduction in risk (Hughes & Carpenter, 2006).

One concern with using nicotine medications for reduction is that concurrent use of NRT and smoking might increase the risk of cardiovascular events (such as heart attacks) or other adverse health effects. Other key findings of the Safety Database address this issue. It is noteworthy that none of the studies that used NRT for reduction reported any serious adverse events, although none of the studies is longer than 5 years.

Another concern is whether promoting reduction might undermine motivation to stop smoking. However, the many studies available suggest that reduction consistently increases future abstinence  among those who do not have immediate plans to quit (Hughes & Carpenter, 2006). As a result of these studies, several regulatory agencies have approved use of NRT to reduce for several months prior to quitting. There are no studies to the effect of promoting reduction on motivation among smokers about to quit in the near future.

A final concern is that harm reduction would result in some people using NRT or other medications for long periods of time (i.e. maintenance therapy to support non-smoking or reduce smoking). The US Lung Health Study, the best test of long-term NRT use, found no increase in cardiovascular or other health problems, even in those who had used NRT and cigarettes concurrently for five years (Murray et al., 1996). Data from a one-year smoking cessation relapse trial with bupropion (Cox et al., 2004) and long-term experience with bupropion, when used for depression, suggest that long-term bupropion use does not appear to produce significant adverse events. Data from a one-year smoking cessation relapse prevention trial with varenicline suggest also that long-term use is not associated with more adverse events (Tonstad et al., 2006).

There are other remaining concerns about reduction, such as: Would promoting reduction send a message that there is a safe level of smoking and thus increase initiation of smoking? Would a reduction alternative cause some who planned to stop abruptly in the near future to instead reduce and thus delay quitting? If so, would this decrease the likelihood of eventually quitting? Would using smokeless tobacco for temporary abstinence produce significant risk?



Anderson P, Hughes JR. Policy interventions to reduce the harm from smoking. Addiction. 2000; 95 Suppl 1: S9-S11.

Institute of Medicine of the National Academies. Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction. Washington DC, 2001.

Royal College of Physicians. Radical strategies for prevention and harm reduction in nicotine addiction. London: Royal College of Physicians; 2008.

Centers for Disease Control and Prevention (US), National Center for Chronic Disease Prevention and Health Promotion (US), Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010.

Hughes JR, Carpenter MJ
. The feasibility of smoking reduction: An update. Addiction. 2005; 100: 1074-1089.

Hatsukami DK, Le CT, Zhang Y, Joseph AM, Mooney ME, Carmella SG, Hecht SS
. Toxicant exposure in cigarette reducers versus light smokers. Cancer Epidemiol Biomarkers Prev. 2006; 15(12): 2355-2358.

Joseph AM, Hecht SS, Murphy SE, Lando H, Carmella SG, Gross M, Bliss R, Le CT, Hatsukami DK. Smoking reduction fails to improve clinical and biological markers of cardiac disease: a randomized controlled trial. Nicotine Tob Res. 2008; 10(3): 471-481.

Tverdal A, Bjartveit K
. Health consequences of reduced daily cigarette consumption. Tob Control. 2006; 15(6): 472-480.

Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005; 14(5): 315-320.

WHO Study Group. The scientific basis of tobacco product regulation. World Health Organ Tech Rep Ser. 2007; (945): 1-112.

Stead LF, Lancaster T
.  Interventions to reduce harm from continued tobacco use. Cochrane Database of Systematic Reviews 2007, Issue 3.

Hughes JR, Carpenter MJ. Does smoking reduction increase future cessation and decrease disease risk? A qualitative review. Nicotine Tob Res. 2006; 8(6): 739-749.

Murray RP, Bailey WC, Daniels K, Bjornson WM, Kurnow K, Connett JE, Nides MA, Kiley JP
. Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Chest. 1996; 109: 438-445.

Cox LS, Patten CA, Niaura RS, Decker PA, Rigotti N, Sachs DP, Buist AS, Hurt RD
. Efficacy of bupropion for relapse prevention in smokers with and without a past history of major depression. J Gen Intern Med. 2004; 19: 828-834.

Tonstad S, Tønnesen P, Hajek P, Williams KE, Billing CB, Reeves KR; Varenicline Phase 3 Study Group
. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006; 296: 64-71.

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