In 1996, the US Public Health Service published its first set of treatment guidelines for tobacco dependence.45 A rich source of evidence-based recommendations, the guidelines firmly established that healthcare providers have an ethical obligation to treat tobacco dependence as a chronic illness, rather than approach it as a mere lifestyle choice. Updated in June of 2000, and again in May 2008, the guidelines provide the reader with dozens of meta-analytic recommendations regarding initial treatment decisions, utility of follow up, relative impact of treatment format, etc.1 We refer all clinicians interested in tobacco-dependence treatment to this comprehensive and influential work. However, the guidelines are limited in terms of practical suggestions to guide specific treatment strategies pertinent to the office setting. The CHEST Tool Kit Committee recognized that, in order to be most useful, recommendations regarding tobacco-dependence treatment need to strike a balance between an open-ended educational approach, where the reader is left to explore the area as needed, and a prescriptive “program” approach, which users may find relatively restricted in application within their environment. The Committee sought a model that would adequately guide the clinician while maintaining relevance to the individualities of practice. We relied heavily on the model developed for the NHLBI’s Guidelines for the Diagnosis and Management of Asthma,364 and offer a Tool Kit that comprises a combination of US Public Health Service guideline recommendations, current standards of practice within the field, and expert consensus advice. The Tool Kit recommendations are guided by four significant assumptions which, taken together, may be equally applicable to virtually any chronic illness, including asthma.
Tobacco dependence is the clinical manifestation of altered central nervous system (CNS) neurobiology. Just as wheezing or shortness of breath is the outward manifestation of abnormal airway inflammation, the compulsion to smoke can be thought of as the outward manifestation of the altered CNS structure and function related to reward, survival, and learning.
- Discontinuing tobacco use is the process of gaining control over the compulsion to administer nicotine via tobacco, a process marked by variability over time.
- Several co-morbid factors may modify the range of possible treatment outcomes; it is the clinician’s responsibility to identify and manage these co-morbidities in order to help patients achieve the best possible outcome.
- As patient advocates, the clinician’s role is not merely to encourage stopping smoking, but to minimize the symptoms of nicotine withdrawal while working toward establishing long-term control over the smoking behavior.
Tobacco Dependence as a Chronic Illness
The brain is a dynamic organ, growing, changing, adapting, and integrating what it learns from the environment. With nicotine exposure, changes occur not only in primary pathways related to the exposure, but also in related modulating pathways such that, over time, irrespective of the inputs, the brain’s output drives the person towards tobacco use and dependence.
The Tool Kit presents a basic outline of the neuropharmacologic effects of nicotine exposure. It is not intended as a complete review of the biologic basis of addictive behaviors, only as a starting point for clinicians to better understand both the nature of patient interventions and a patient’s reluctance to stop using tobacco. It is our intention to provide the reader with a rational basis for the use of pharmacotherapy as well as a framework within which to refine the therapeutic approach to these patients.
The Process of Establishing Control
In a general sense, the “process of stopping smoking” may be thought of as three overlapping phases of progressive control: the initiation of continuous nonsmoking, the struggle to prevent slips, and the avoidance of relapse.46 While relapse has traditionally been viewed as the primary outcome of treatment trials, strategies that focus on the processes mediating progression from a minor slip to a resumption of smoking behaviors have had a substantial influence on treatment outcomes.47 Tobacco-dependent patients attempting to stop smoking will pass through a “high risk period” following their Target Stop Date, during which they may sustain one or more slips, or lapses.48 Most, but not all, tobacco-dependent patients stop smoking for at least one day on their chosen Target Stop Date. After this, the majority will go back to smoking if left unassisted and untreated. The incidence of relapse is depicted in the table below.
|Time Since Target Stop Date (Days)||Incidence of Relapse (%)|
Often, resumption of regular smoking begins with a minor lapse of just one or two cigarettes. At this critical juncture, tobacco-dependent patients will either reaffirm their desire to stop and adjust their approach accordingly, or will rapidly revert to regular smoking routines.49 Smoking lapses therefore represent an important clinical juncture between stopping smoking and relapse. Tool Kit recommendations focus on effective tobacco-dependence treatment through an active process of managing lapses to minimize their frequency and reduce the likelihood that a lapse will progress to relapse.
The severity of craving for cigarettes and nicotine withdrawal symptoms directly predict cigarette lapse and complete treatment failure, i.e., relapse to regular cigarette smoking.50 All FDA-approved tobacco-dependence medications, including nicotine medications,51-53 bupropion,54 and varenicline,55 significantly reduce severity of craving for cigarettes and other nicotine withdrawal symptoms. The better craving for cigarettes and other nicotine withdrawal symptoms are suppressed, the better the treatment outcome, the less the likelihood of relapse, and the less the likelihood of a lapse progressing to complete treatment failure.50, 53, 56
Preventing Lapses with Aggressive Pharmacotherapy (The “Controller” Paradigm)
Several observations led the Tool Kit Committee to adopt rather aggressive strategies for achieving control of withdrawal symptoms using Controller Medications. Given that absorption of nicotine from the patch delivery system is highly variable, the concept of individualized dosing of nicotine has been tested for efficacy. Findings from several independent studies suggest that individualizing patch dose to achieve targeted serum nicotine level during treatment can significantly improve treatment results, including control over withdrawal symptoms.57,58 Accomplishing this, however, requires substantially higher patch doses than have been traditionally recommended, generally upwards of two or more patches.59-61The main barrier to individualizing patch recommendations is the infeasibility of measuring serum nicotine concentrations in a clinical setting. In lieu of laboratory guidance, the Tool Kit Committee advocates an approach wherein the main goal of aggressive therapy is the effective relief of withdrawal symptoms. High-dose NRT reduces withdrawal symptoms and craving,53 can eliminate some symptoms entirely53 and reduces lapses and treatment failure (relapse).50
The data guiding the use of multiple Controller Medications in combination are revealing, rapidly growing, and consistently robust (See Pharmacologic Treatment, “Combination Pharmacotherapy – The Current Treatment Standard“). In a large randomized clinical trial, designed specifically to answer this question, treatment with sustained-release bupropion in combination with a nicotine patch resulted in significantly higher long-term rates of continuous nonsmoking than use of either the nicotine patch alone or placebo. Continuous nonsmoking rates were higher with combination therapy than with bupropion alone.62The group receiving combination Controller therapy experienced better relief of their withdrawal and craving symptoms. This combination of two Controller medications – bupropion + nicotine patch – is both FDA-approved and is one of three combinations specifically recommended in the 2008 Public Health Service Guidelines with an “A” rating, for strength of evidence showing treatment effectiveness.
Tobacco-Dependence Treatment of Schizophrenic Patients with Combination Medications: In a separate study, subjects with schizophrenia were placed on bupropion + dual nicotine medications (patch and gum) and experienced a greater rate of smoking reduction at weeks 12 and 24, and a greater continuous nonsmoking rate at week 8 than the dual-nicotine medications, alone, control group.63Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term continuous nonsmoking rates than treatment with the nicotine patch alone or placebo.64The compelling similarity of these findings across trials suggests that combination Controllers, specifically bupropion + nicotine patch, can provide greater benefit to tobacco-dependent patients who have had difficulty stopping cigarette use with only one Controller, who are severely nicotine dependent, or who suffer from psychiatric co-morbidities that can influence treatment outcomes.
Managing Lapses with Acute Nicotine Administration (The “Reliever” Paradigm)
Nicotine replacement therapy (NRT) has repeatedly been shown to improve smoking treatment outcomes in general. Aggressive use of NRT has also been shown to decrease the risk of progression from lapse to relapse. Active treatment appears to reduce the risk of both a second lapse (Hazard Ratio=0.54) and relapse (HR=0.22).This therapeutic effect might be mediated via decreased reinforcement experienced during a smoking lapse. Acute cravings, often provoked by exposure to smoking cues, can be effectively managed by using acute delivery forms of nicotine following exposure to smoking cues.
Effective, “just-in-time” interventions should be offered to all patients and implemented as needed. Several studies have shown that combining two types of NRT – nicotine patch, as a controller medication that produces relatively steady levels of drug in the body, and ad libitum dosing, using reliever nicotine medication, such as gum or nasal spray, adjusted acutely by the patient in response to specific nicotine withdrawal symptoms – is more effective in promoting prolonged nonsmoking than providing either alone.66-70The 2008 US Public Health Service Guidelines recommends combining the nicotine patch with a self-administered form of NRT (Controller + Reliever medications), especially in those who have poorly controlled nicotine withdrawal symptoms with a single medication in the past (Strength of Evidence = A).1Encouraging patients to use such combined treatments is an important role for the physician, since patients often have preconceived reservations, particularly safety concerns, about using combination NRT.
Preventing Relapse with Long-Term Pharmacotherapy (The “Step-Down” Approach)
Clearly, patients are best served by an approach to pharmacotherapy that neither unnecessarily prolongs the duration of treatment for patients who no longer require it, nor prematurely discontinues it in those who do. Because the relationship between effectiveness and duration of therapy for any chronic illness is not simple or linear, decisions regarding length of tobacco-dependence treatment should be a matter of clinical judgment rather than a fixed schedule. There is far more to be lost by too little treatment than there is by too much. None of the medications used for the treatment of tobacco dependence contain any of the pathogenic components found in tobacco smoke71or result in strong dependence.72Therefore, while it is certainly preferable to taper medications at a comfortable rate, clinicians should not feel compelled to discontinue medications if, in their judgment, that would undermine control of nicotine withdrawal symptoms. (See Pharmacologic Treatment, “Duration of Use” for further discussion on this topic.)
For varenicline in particular, converging lines of investigation suggest that prolonged periods of treatment help tobacco-dependent patients maintain continuous nonsmoking longer than “standard” treatment periods. For example, while the recommended treatment period for varenicline is 12 weeks, an additional 12 weeks of treatment confers an advantage, with continuous nonsmoking rates significantly higher than in those who did not receive the additional treatment.73Treatment with 52 weeks of varenicline 1 mg BID was generally safe and was associated with a continuous nonsmoking rate that maintained a plateau of nearly 40% throughout the treatment period.74 The data concerning long-term use of nicotine replacement products is more mixed. Though clearly more effective than no treatment, it is less clear whether sustained use of NRTs results in improved long-term outcomes. It is important to note that the variability in effect may be confounded by other treatment variables, such as dose, route of administration, etc.75 Observations made on data collected during the Lung Health Study suggest that a large portion of sustained nonsmoking tobacco-dependent patients, when left to make their own decisions about treatment duration, were still using NRT 12 months after starting treatment76and some for as long as 5 years, with no serious side effects.293 More recent studies have unequivocally shown that longer treatment – longer than typically suggested in the drug label – produces better treatment outcome and a higher percentage who are able to stop smoking. These observations led the 2008 US Public Health Service Guidelines to conclude that, “For some patients, it may be appropriate to continue medication treatment for periods longer than usually recommended” and that “continued use of such [tobacco-dependence] medications clearly is preferable to a return to smoking with respect to health consequences. Finally, it should be noted that the medication treatment that produced the largest effects on [nonsmoking] rates … involved long-term nicotine patch therapy + ad libitum NRT Table 6.26.”1