Treatment of Nicotine Dependence


There are an increasing number of options available for the treatment of nicotine dependence. As noted above, nicotine dependence is a chronic, relapsing disorder, and treatment should be approached from this perspective. The U. S. Public Health Service’s Clinical Practice Guideline on Treating Tobacco Use and Dependence is a comprehensive review of smoking cessation research, with recommendations based on numerous meta-analyses. It is the best resource for evaluating currently available treatments, and therefore it is the basis for most of the conclusions that we present here.


To date, there are seven FDA-approved medications that reliably increase long-term abstinence rates. These includefive nicotine replacement therapies (NRT) (gum, transdermal patch, inhaler, nasal spray, and lozenge), and two non- nicotine medications (bupropion SR, and varenicline). NRTs are designed to wean smokers gradually off nicotine in a manner that reduces the severity of withdrawal symptoms and cravings to smoke. They are typically used during the first 8–12 weeks of tobacco abstinence. Although the products vary in their routes of nicotine delivery (with the patch providing the most consistent delivery and stable blood levels), their efficacy levels are roughly equivalent, with odds ratios of approximately 2. 0 compared to placebo, producing 6-month abstinence rates of approximately 20–25%. Thus, choice of NRT can be based on patient preference and availability (gum, patch, and lozenge are available over the counter). These products have relatively mild side-effect profiles that are primarily related to their route of administration (e. g., skin irritation from the patch, nasal passage irritation from the spray).

Bupropion, which is also prescribed as an antidepressant, appears to function by inhibiting the neuronal reuptake of dopamine and norepinephrine. Unlike NRTs, the smoker begins taking bupropion 1 week prior to the target quit-smoking day. Contraindications include a history of seizure disorders or factors known to increase the risk of seizures (e. g., bulimia or anorexia nervosa, serious head trauma, alcoholism). The efficacy of bupropion is similar to the NRTs

Varenicline is a partial nAChR agonist. It reduces withdrawal symptoms and cravings, and it may also reduce the satisfaction obtained from smoking. As with bupropion, the patient begins varenicline use approximately 1 week prior to quitting smoking. Odds ratios for varenicline to date are higher than for the other smoking cessation medications, with this drug approximately tripling the odds of quitting smoking. Although the primary side effect of varenicline is nausea, the drug is receiving renewed scrutiny due to post-marketing reports of changes in behavior, agitation, depressed mood, suicidal ideation, and actual suicidal behavior. Consequently, the FDA issued a Boxed Warning in 2009, and product labeling was revised to alert patients and healthcare providers to the possibility of these neuropsychiatric effects. Then in 2009, the FDA issued an advisory for both varenicline and bupropion and required boxed warnings about neuropsychiatric symptoms on both products. Follow-up studies are ongoing to quantify the frequency of these adverse reactions. Meanwhile, physicians and patients must weigh the potential health benefits associated with the greater efficacy of this product against the serious but apparently rare potential risks that have been reported.

Recent research reviewed in the Clinical Practice Guideline also supports the use of combination pharmacotherapy. Specifically, evidence supports the use of the nicotine patch combined with either another NRT or bupropion SR, which might be considered for highly nicotine-dependent patients or those unable to quit with a single medication ().

Behavioral Counseling

An unfortunate consequence of the progress over the past 25 years in the development of pharmacotherapies for treating nicotine dependence has been that both patients and providers increasingly fail to recognize the benefits of counseling. The most recent Clinical Practice Guideline clarifies that the highest rates of cessation tend to be achieved with a combination of medication and counseling. These two strategies tend to complement each other, with medication reducing the severity of withdrawal symptoms and nicotine cravings, while counseling teaches information and cessation-related skills, as well as providing social support and motivational enhancement.

Counseling approaches can be ordered by level of intensity, ranging from very brief physician advice, through very intensive multi-session individual or group counseling. In general, there is a monotonic relationship between the level of intensity and the efficacy of counseling interventions. Nevertheless, even as few as 3 min of physician advice and assistance can produce significant increases in cessation rates (with 6-month abstinence of approximately 13–14%), which may cumulatively produce dramatic effects at the population level. See the Clinical Practice Guidelines for specifics about the “5 A’s” of brief counseling: Ask, Advise, Assess, Assist, and Arrange Follow-up.

At the most intensive end of the counseling continuum, smoking cessation clinics often provide 4–8 weeks of counseling that involves: teaching smokers the nature of nicotine addiction, including the symptoms and time course of nicotine withdrawal; training in recognizing and avoiding high-risk situations that “trigger” urges to smoke; training in cognitive and behavioral skills to cope with cravings to smoke; and training in how to respond to an initial smoking slip or “lapse” should it occurs, so that it does not progress to a full relapse to regular smoking. In addition, intensive counseling usually includes valued social support and motivational encouragement. Intensive counseling without pharmacotherapy can produce abstinence rates in the range of 15–25%. Treatment manuals are available.

Two nontraditional modalities for providing behavioral counseling include self-help and telephone quitlines. Self-help refers to the provision of informational materials (traditionally in the form of pamphlets and brochures, but increasingly provided via video or Internet websites). In general, self-help interventions for smoking cessation have produced very low efficacy, but there is emerging evidence that increasing the focus of self-help materials may enhance their efficacy. For example, self-help booklets written specifically for individuals who had recently quit smoking, with a goal of reducing smoking relapse, have been found to be efficacious and highly cost effective. Moreover, interventions that are computer tailored to the demographic and psychological characteristics of each individual smoker usually show slightly superior efficacy compared to standard, untailored self-help materials

Telephone quitlines represent the second nontraditional counseling modality. These quitlines are now available in each state and can be accessed through a single telephone number (1-800-QUITNOW). Individual quitlines differ in the services that they provide (e. g., provision of materials, local referrals, and pharmacotherapy), but they all offer some degree of counseling. Two recent meta-analyses concluded that quitlines were efficacious, which translates into differential long-term abstinence rates of at least 3–5%.

Although the less intensive forms of counseling (including brief physician advice, self-help, and telephone quitlines) produce lower cessation rates than more intensive behavioral counseling, this must be balanced against the much higher potential reach of these interventions. Therefore, with sufficient dissemination, such minimal intervention may nevertheless produce significant public health impact.


Selections from the book: Joris C. Verster • Kathleen Brady Marc Galanter • Patricia Conrod Editors “Drug Abuse and Addiction in Medical Illness: Causes, Consequences and Treatment”, 2012.