Tobacco Dependence and Treatment for APRNs Nursing CE Course

e Use And Prevention, 2017). There are about 600 ingredients in cigarettes, and tobacco smoke produces more than 7,000 different chemicals; nearly 70 are known carcinogens (cancer-causing substances). Some of the chemical constituents of cigarettes are outlined in Table 1 (American Lung Association, 2021; Irish Cancer Society, 2021).

In 2014, the Independent Scientific Committee on Drugs convened an international expert panel to rank 12 nicotine-containing products based on their relative harm using the multi-criteria decision analysis (MCDA) approach. Their findings revealed that cigarettes are by far the most harmful (with a score of 100 out of 100) to individuals and others based on 14 independent criteria. Nicotine replacement (NRT) products such as patches and nasal sprays received low scores of 2, whereas small cigars (score 64), pipes (score 21), cigars (score 16), and water pipes (score 14) carried additional harm. This committee credited the bulk of smoking’s damage to CO, tobacco-specific nitrosamines (TSNAs), and nitric oxide (Nutt et al., 2014). A separate study of toxicant exposure in combustible tobacco products (CTPs) listed the potent toxins found in cigarette smoke to include TSNAs, metals such as lead and cadmium, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs; Goniewicz et al., 2018). 

Electronic Cigarettes (E-Cigs)

Historically, most warnings against smoking have centered on the dangers of tar and CO found in conventional cigarettes. While the overall rate of cigarette smoking has declined, US youth are increasingly experimenting with alternative tobacco products, especially e-cigs. According to a report released by the US Surgeon General, the use of e-cigs (vaping) increased by 900% among high-school students between 2011 and 2015 (HHS, 2016). E-cigs are sold in nearly 8,000 flavors—including cotton candy, apple pie, and gummy bear—to attract younger users. They have been cited as the most used tobacco product among youth since 2014 (CDC, 2020b; Siqueira & the Committee On Substance Use And Prevention, 2017). While the Independent Scientific Committee on Drugs reported that e-cigs were substantially less harmful than combustible (traditional) cigarettes in their 2014 report, their stance was based on a lack of evidence. Their statement on the reduced harms of e-cigs ignited a media frenzy spawning the increased use of e-cigs, especially among youth (Nutt et al., 2014). Since the publication of this report, additional research has disputed their findings, revealing the devastating health consequences of e-cigs. 

E-cigs consist of a reservoir for liquid and a heating element (atomizer) that creates an aerosol from the liquid. The fluid is composed of a solvent (typically vegetable glycerin or propylene glycol), and in addition to added flavors, has various concentrations of nicotine (Dinakar & O’Connor, 2016). In addition to utilizing different materials and copious heating coils, e-cig devices can currently attain a power output that exceeds the 2014 models by up to 20 times. This higher power increases the harm of e-cigs by generating more aerosol and exposing users to more nicotine and other toxicants. Furthermore, modern-day e-cigs increase bystander exposure (secondhand smoke) to their harmful aerosol components as users exhale more aerosol. Even at room temperature, the liquids in e-cigs can be unstable, producing irritating acetal compounds and carcinogens (Eissenberg et al., 2019). According to a review from National Health Interview Surveys (NHIS), vaping is associated with significant cardiac changes related to chronic CVD. E-cig users have higher risks of heart attack, stroke, and circulatory problems than non-users (Vindhyal et al., 2019)

In 2018, the National Academies of Sciences, Engineering, and Medicine (NASEM) published a report on the public health consequences of e-cigs. They cited the Family Smoking Prevention and Tobacco Control Act of 2009, which states that all products introduced after February 15, 2007, must be shown to have a net positive health impact on both users and the community. Their expert panel concluded that while the vapor from e-cigs produced fewer and lower levels of toxicants than CTPs, the overall benefit-to-harm ratio would be determined by three factors: the effect of e-cigs on youth initiation of CTPs, the impact of e-cigs on adult cessation rates of CTPs, and their intrinsic toxicity. Among youth and young adults, the reported use of e-cigs is now significantly higher than the reported use of CTPs. The report cited an increase in e-cig use from 2011 to 2015, with a potential stabilization/decrease in 2016. They contend the current evidence allows for the following conclusive findings (Stratton et al., 2018):

• E-cig use increases the airborne particulate matter and nicotine in the indoor environment.
• Most e-cigs contain and emit numerous potentially toxic substances, including nicotine; however, exposure depends on the device used, the liquid used, and how the product is operated.
• E-cig devices can explode, causing burns and other projectile injuries.
• Intentional or accidental exposure to e-cig liquid (ingestion, eye contact, skin contact) can result in seizures, anoxic brain injury, vomiting, and lactic acidosis. Drinking or injecting e-cig liquid can be fatal.

Nicotine Addiction

More than two-thirds of smokers report a desire to quit, and thousands attempt to stop every day. In 2018, 55.1% (21.5 million) adult cigarette smokers tried to quit during the past year, and 7.5% (2.9 million) were successful (CDC, 2020a, 2021c). According to the HHS (2020), most individuals who try to quit eventually succeed, as 3 in 5 adults who have ever smoked have quit. Since 2002, there have been more former smokers than current smokers (HHS, 2020). Due to its highly addictive nature, nicotine is responsible for many failed cessation attempts, and most users make multiple attempts before they stop permanently. 

Nicotine dependence occurs when people need the nicotine, as the user’s body has become accustomed to having the drug. Nicotine dependence has physiological and behavioral mechanisms. Nicotine produces a temporary increase in endorphins within the brain's reward circuits, eliciting a slight, brief period of euphoria. It increases levels of the neurotransmitter dopamine in the brain, reinforcing the behavior of taking the drug. It also temporarily bolsters aspects of cognition, such as improving a person’s attention span. For tobacco users, the long-term brain changes induced by continual nicotine exposure lead to addiction. The National Institute on Drug Abuse (NIDA) defines addiction as compulsive drug-seeking and use, even in the face of adverse health consequences. Dependence involves unpleasant withdrawal symptoms when tobacco is withheld, such as irritability, craving, depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite. Furthermore, withdrawal symptoms can begin within a few hours after the last cigarette, making it harder to sustain the desire to quit (Prochaska & Benowitz, 2019; NIDA, 2020). Nicotine may make the brain more susceptible to addiction by boosting dopamine concentrations and “prime” the brain for other addictions; however, research in this area is ongoing (Siqueira & the Committee On Substance Use And Prevention, 2017).

Benefits of Quitting 

According to the HHS (2020), smoking cessation is beneficial at all ages because it improves overall health, dramatically reduces the risk of developing smoking-related diseases, and improves quality of life. The CDC, HHS, and other anti-smoking organizations have generated various public campaigns and educational programs on the benefits of smoking cessation (CDC, 2020a; HHS, 2020). The health benefits of quitting start nearly immediately and extend for decades. See Table 2 for an overview of the time-sensitive health benefits of smoking cessation (CDC, 2020a; HHS, 2020).

According to the HHS (2020), quitting smoking reduces premature death, can add up to a decade to a person’s life expectancy, and reduces the risk of numerous adverse health effects, including CVD, COPD, and at least 12 types of cancer. Furthermore, quitting smoking reduces the financial burden on the healthcare system and society (HHS, 2020).

Treatment Options for Tobacco Dependence

While multiple evidence-based treatment options are available for tobacco dependence, the HHS (2020) has shown they are widely underutilized. Fewer than 1 in 3 adults who try to quit smoking have used proven cessation treatments. The HHS (2020) highlights the need for coordinated action at the clinical, system, and population levels to increase access to treatment. Since tobacco dependence has behavioral (i.e., the habit of using tobacco) and physiological (i.e., addiction) roots, effective treatment should address both aspects. According to a 2019 systematic review conducted by the US Preventive Services Task Force (USPSTF), there is strong evidence that various pharmacologic and behavioral interventions (individually and in combination) effectively contribute to smoking cessation for adults. The review also noted that among pregnant women, behavioral interventions are adequate, as there is a lack of evidence regarding the safety and efficacy of pharmacologic therapies in this population (Patnode et al., 2019). The HHS (2020) has endorsed smoking cessation interventions as successful and cost-effective, promoting behavioral treatments such as individual, group, internet-based, and telephone counseling, as well as seven pharmacotherapies approved by the US Food & Drug Administration (FDA).     

Behavioral Approaches

Many studies have demonstrated that behavioral counseling and medication interventions increase smoking cessation compared with self-help materials or no treatment. There are several behavioral support resources for patients who want to quit using tobacco. Combined with ongoing monitoring, support, and treatment, referring patients to the Quitline (i.e., 1-800-QUIT-NOW) or another cessation resource can improve their chances of quitting. Quitline is a free and confidential telephone-based support staffed by trained counselors available across the US. Internet-based support systems connect patients to others struggling with tobacco dependence and offer cessation-related links and resources for more information. Federally funded text-messaging programs can help patients looking for on-demand encouragement, positive reinforcement, and real-time support. Over recent years, there has also been an influx of smartphone apps that offer ongoing and easily accessible support (CDC, 2021b). 

According to the American Psychiatric Association (APA, 2020), psychotherapy can be utilized to enhance a patient's capacity to make behavioral changes (e.g., smoking cessation). Types of psychotherapy with demonstrated efficacy in treating tobacco use and nicotine dependence include cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT). CBT is among the most well-cited and established forms of psychotherapy, as it has the most evidence supporting its clinical utility. The overarching features of CBT include short-term, problem-focused intervention that employs both cognitive and behavioral techniques. CBT teaches patients to restructure cognitive distortions and self-defeating behaviors and replace them with more accurate thoughts and functional behaviors. The focus is narrowed to the patient's current problem(s) to provide practical solutions and strategies to manage them successfully (David et al., 2018). In CBT, patients learn to reframe negative or self-defeating thoughts, making it easier to cope with cravings and unpleasant emotions associated with quitting, including withdrawal symptoms. Thus, CBT treatments may increase the likelihood of successful smoking cessation (GoodTherapy, 2020). 

ACT is an action-oriented, process-based intervention that promotes mindfulness techniques to achieve psychological flexibility and help patients live more authentic lives. Psychological flexibility refers to being present, remaining open-minded, and acting consistently with core beliefs. ACT encourages patients to develop a new and positive relationship with their underlying cognitions. Patients learn the consequences of avoiding, denying, and suppressing their inner emotions. By recognizing these challenges and accepting their feelings as appropriate responses to life events, patients learn to behave in ways consistent with their values. ACT encourages patients to acknowledge unwanted emotional experiences as unavoidable aspects of life and forgo viewing them as problems or symptoms. It promotes acceptance of circumstances as they come without attempting to change inevitable things (Hacker et al., 2016). For example, ACT encourages patients to recognize and accept their urges to smoke, with the understanding that these sensations are temporary and will dwindle over time. ACT principles are employed by various smoking-cessation smartphone apps to help smokers achieve enhanced psychological flexibility through education, practice, and committed action (GoodTherapy, 2020; HHS, 2020). 

The HHS (2020) reviewed the available behavioral interventions for smoking cessation and found sufficient evidence to conclude that behavioral counseling and cessation medications (see next section) are independently effective in increasing smoking cessation but even more effective when combined. Furthermore, the HHS found sufficient evidence supporting Quitline counseling services' clinical usefulness and efficacy when provided alone or in combination with medications. In addition, text-messaging services are practical and effective mechanisms for improving success rates, especially if they are interactive or offer personalized text responses. Finally, HHS (2020) also has supported the value of internet-based behavioral interventions to enhance smoking cessation, stating that they can be more effective when they contain behavioral change techniques and interactive mechanisms for each user.

For a detailed account of the various types of psychotherapies and their clinical utility, refer to the Psychotherapy NursingCE course. 

Nicotine Replacement Therapy (NRT)

NRT was first introduced in the late 1970s to assist smokers with weaning gradually off nicotine, the most physically addicting component of cigarettes. Nicotine undergoes first-pass metabolism, which limits the effectiveness of orally ingested formulations. Therefore, NRT options available over the counter (OTC) in the US include patches, gum, and lozenges. Nasal sprays and inhalers are also available but require a prescription from a licensed prescriber (See Table 3; American Academy of Family Physicians [AAFP], 2019). 

NRT has been shown to improve smoking cessation rates by 50%-70%. Combined therapy (e.g., using two or more NRT products, such as a patch and gum) is more effective than monotherapy. The transdermal patch is the slowest and longest-acting option, with serum concentrations peaking in 6-8 hours. The most reported adverse effects include insomnia, abnormal dreams, and pruritus, but these improve quickly once the patch is removed. The gum, lozenge, and inhaler formulations peak in 20-60 minutes. Those who use nicotine gum most commonly report flatulence, indigestion, nausea, an unpleasant taste, hiccups, and a sore throat, mouth, or jaw. Adverse effects related to the inhaler include a dry cough and irritation of the mouth and throat. The nasal spray offers the fastest onset of action, peaking in the central nervous system (CNS) within 5-20 minutes; it most closely mimics the effects of smoking a cigarette. Most NRTs are recommended for use for up to 3 months (except the oral inhaler, which may be used for up to 6 months), as prolonged use increases the risk of throat and nose irritation. NRTs should not be abruptly discontinued and should be tapered before stopping (AAFP, 2019; Drugs for Tobacco Dependence, 2016). NRT was shown statistically to improve abstinence rates among smokers compared to placebo in the EAGLES trial. In this trial involving over 8,000 adult smokers, the NRT group showed 23.4% and 15.7% abstinence rates at 12 and 24 weeks, respectively, compared to 12.5% and 9.4% in the placebo group (Anthenelli et al., 2016). 

Cunningham and colleagues (2016) mailed nicotine patches to 500 adults in Canada who smoked at least 10 cigarettes per day and compared their self-reported abstinence rates to 499 smokers who did not receive patches. The study group reported a 7.6% abstinence rate, while the control group reported 3% at 30 days. Saliva samples were also requested to validate abstinence, but only half of the study participants returned samples, and only 14 samples (2.8%) could be confirmed negative. Interestingly, while 421 of 500 participants in this study reported receiving the patches, only 246 reported using them. Furthermore, only 46 reported using all patches at the 8-week follow-up point (Cunningham et al., 2016). In a randomized trial involving 657 adult smokers in New Zealand, nicotine patches resulted in a quit rate of 5.8% in that group and 7.3% when combined with e-cigs. In addition, when NRT was studied in pregnant women, its use resulted in decreased smoking in the second trimester and better child development outcomes at 2 years (Dinakar & O’Connor, 2016). 

Pharmaceuticals

Bupropion sustained-release (SR; Zyban) and varenicline (Chantix) are FDA-approved prescription medications for smoking cessation. Bupropion SR (Zyban) is an atypical antidepressant that primarily functions as a norepinephrine and dopamine reuptake inhibitor. It was developed to treat depression as it helps improve concentration, focus, and reduces hyperactivity but was also found to have nicotinic receptor-blocking activity. It has been shown to double smoking cessation rates in short-term studies versus placebo, with roughly similar efficacy to NRT. Bupropion SR (Zyban) has been demonstrated statistically to improve abstinence rates among smokers compared to placebo in the EAGLES trial with 22.6% and 16.2% abstinence rates at 12 and 24 weeks, respectively, compared to 12.5% and 9.4% in the placebo group (Anthenelli et al., 2016). Prescribing guidelines recommend a dosing schedule of 150 mg PO daily for 3 days, followed by 150 mg PO BID. The dose should not exceed 300 mg per day, and patients should be counseled to allow at least 8 hours between twice-daily doses. Bupropion SR (Zyban) should be started 1-2 weeks before the target quit date (TQD). The duration of therapy is typically 7-12 weeks, but maintenance therapy can continue for up to 6 months in some patients. Dose tapering is not necessary when discontinuing treatment. The most reported adverse effects include insomnia, dry mouth, headaches, nausea, anxiety, agitation, increased motor activity, tremors, and tics. Patients should be advised to avoid taking bupropion SR (Zyban) at bedtime to minimize insomnia. The drug carries a 0.1% risk of seizures and therefore is contraindicated in patients with underlying seizure disorders and should not be given to patients with a history of stroke, brain tumor, brain surgery, or traumatic brain injury. Additional contraindications include a current or prior diagnosis of bulimia or anorexia nervosa, simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines, and current monoamine oxidase inhibitor (MAOI) use or in the preceding 14 days. APRNs should perform a complete medication reconciliation before prescribing bupropion (Zyban) to ensure patients are not taking other medications known to lower the seizure threshold (AAFP, 2019). 

Varenicline (Chantix) works by blocking nicotine receptors in the brain. As a partial agonist, it binds selectively to 𝛂2β4 nicotinic acetylcholine receptors, inhibiting dopaminergic activation produced by smoking to decrease cravings and withdrawal symptoms. It is more effective than NRT monotherapy or bupropion SR (Zyban) and roughly as effective as combination NRT (Drugs for Tobacco Dependence, 2016; HHS, 2020). Varenicline (Chantix) should only be prescribed to patients 18 years and older. Prescribing guidelines recommend the following dosing schedule:

• days 1–3: 0.5 mg PO daily
• days 4–7: 0.5 mg PO BID 
• weeks 2–12: 1 mg PO BID (AAFP, 2019)

Ideally, varenicline (Chantix) should be started a week before the TQD, and the duration of therapy is typically 12 weeks; an additional 12-week course may be given to some patients. Patients may initiate treatment up to 35 days before their TQD. Alternatively, patients may reduce smoking over 12 weeks of therapy before quitting altogether and continue treatment for an additional 12 weeks. A maximum dose of 0.5 mg twice daily is advised for patients with renal impairment (i.e., creatinine clearance < 30), as this medication can cause renal failure and kidney stones. For patients with end-stage renal disease (ESRD) on hemodialysis, a maximum dose of 0.5 mg once daily is recommended (AAFP, 2019). The most common adverse effects include nausea, insomnia, vivid dreams, headaches, constipation, vomiting, flatulence, and xerostomia, with increased adverse effects reported when used in combination with NRT. APRNs should counsel patients to take varenicline (Chantix) with a full glass of water after eating to decrease GI upset. Sleepwalking, agitation, and drowsiness have been reported. Some observational studies have demonstrated an increase in neuropsychological symptoms or exacerbations of previously existing psychiatric illness and suicidal behavior, as well as an increased rate of cardiovascular events (Drugs for Tobacco Dependence, 2016; Singh & Saadabadi, 2021). However, the FDA-mandated EAGLES trial showed no statistically significant increase in moderate to severe neuropsychological adverse events for patients taking varenicline (Chantix) versus placebo. The study’s findings also revealed a statistically significant improvement in abstinence rates with varenicline (Chantix) at 12 and 24 weeks (33.5% and 21.8%, respectively) compared to all other groups (Anthenelli et al., 2016). In a separate trial involving over 900 adults who reported smoking at least five cigarettes per day, varenicline (Chantix) was compared with an NRT patch as well as a combination of a patch and a lozenge. After 12 initial weeks of treatment, the study showed no significant difference in sustained abstinence at follow-up at 26 weeks. The varenicline (Chantix) group did report more adverse effects, such as abnormal dreams, insomnia, nausea, sleepiness, constipation, and indigestion (Baker et al., 2016).  

Although not approved in the US, cytisine has been safely used in eastern Europe and many other countries for smoking cessation since the 1960s. Cytisine is a partial agonist of nicotinic acetylcholine receptor 𝛂4β2 and is primary derived from the Cytisus laburnum plant. Clinical trials have demonstrated promising results, linking cytisine to an increased likelihood of smoking cessation as a practical, low-cost medication option. The most common side effects include GI symptoms such as nausea, vomiting, dyspepsia, upper abdominal pain, and a dry mouth. The rationale for its lack of approval in the US is unclear, but critics blame its generic structure and pharmaceutical market exclusivity as the primary obstacles. Cytisine’s low selling price offers minimal financial incentives for companies to pursue costly regulatory approvals in the US (Karnieg & Wang, 2018; Tutka et al., 2019).  

E-Cigs and Smoking Cessation

As described earlier, e-cigs have many negative health consequences and are not approved by the FDA for smoking cessation. Earlier studies demonstrated a small benefit of e-cigs over NRT and other smoking-cessation options, but as newer evidence has emerged regarding the poor health outcomes with e-cigs, research has shifted away from making direct comparisons. A small, randomized trial of 300 smokers not intending to quit found the use of an e-cig with 5.4 or 7.2 mg of added nicotine led to significantly more participants reporting complete abstinence from cigarettes at 12 weeks compared to e-cigs without added nicotine. A larger randomized trial of over 650 smokers intending to quit compared NRT patches, an e-cig (with 16 mg added nicotine), and a placebo e-cig. Their findings demonstrated no statistically significant difference between the groups at 6 months, with abstinence rates ranging from 4.1% (placebo group) to 7.3% (e-cig with nicotine). A meta-analysis of 38 trials of smokers showed that those who used e-cigs were 28% less likely to quit smoking than those who did not (Drugs of Tobacco Dependence, 2016). The NASEM report (2018) found limited evidence that e-cigs effectively promoted smoking cessation. 

Other Alternatives

Some have proposed that smoking rates in the US could be drastically reduced with legislative action. Various groups have proposed federal harm taxes, based on a similar system in Sweden, in which all tobacco products are taxed based on their relative harm. Others have proposed federal regulations regarding the amount of nicotine that manufacturers of cigarettes can include in their products. One study used a simulation model based on the opinions of 8 experts to predict the public health effects of such a federal regulation on cigarettes. It concluded that initiation rates would steadily drop as cessation rates increased: only 1.4% of the country would be smoking cigarettes by 2060. The rate of all tobacco use would gradually decrease to 11.6% by 2060. They predicted 16 million would-be smokers would be spared by 2060 and 33 million by 2100, and 8.5 million tobacco-related deaths would be avoided by 2100 (Apelberg et al., 2018).

Additional cessation treatments have been tried. For example, a systematic review and meta-analysis on the effect of mindfulness meditation looked at 10 randomized trials and found no statistically significant effect on abstinence rates or the number of cigarettes per day (Maglione et al., 2017). A similar study looked at financial incentives compared to e-cigs or NRT. Over 6,000 adult smokers were randomized to one of four groups: free NRT or pharmaceuticals with secondary e-cigs if desired, free e-cigs, or two different financial-incentive programs (reward versus deposit) for smoking cessation. Both financial-incentive groups were also offered free NRT or pharmaceuticals with a secondary free e-cig if desired. The results showed only 80 confirmed cases of abstinence; abstinence rates were significantly higher in the financial-incentive groups (2% and 2.9%) versus the usual-care group (0.1%; Halpern et al., 2018).

The APRN Role in Smoking Cessation

According to the HHS (2020), 4 of every 9 adult cigarette smokers who saw a healthcare professional did not receive smoking cessation advice during the past year. Even brief advice to quit (e.g., typically under 3 minutes) from a clinician improves cessation rates and is highly cost-effective. APRNs have a responsibility to educate patients on the health consequences of tobacco use and the health benefits of quitting. APRNs working with children and adolescents should offer preventative counseling, as preventing tobacco use among youth is critical to ending the tobacco epidemic. APRNs should integrate cessation discussions and interventions into all patient encounters, as they are well-positioned to facilitate increased access to treatments. Through environments that encourage patients to quit smoking and interventions to make quitting easier, patients are more likely to be receptive to the information and take their healthcare provider’s concerns seriously (HHS, 2020). 

References 

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