Tobacco, Nicotine, and E-Cigarettes Research Report
What are treatments for tobacco dependence?

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There are effective treatments that support tobacco cessation, including both behavioral therapies and FDA-approved medications. FDA-approved pharmacotherapies include various forms of nicotine replacement therapy as well as bupropion and varenicline. Research indicates that smokers who receive a combination of behavioral treatment and cessation medications quit at higher rates than those who receive minimal intervention.^{37,40,162–167} Interventions such as brief advice from a health care worker, telephone helplines, automated text messaging, and printed self-help materials can also facilitate smoking cessation.¹⁶³ Cessation interventions utilizing mobile devices and social media also show promise in boosting tobacco cessation.¹⁶⁸ It is important for cessation treatment to be as personalized as possible, as some people smoke to avoid negative effects of withdrawal while others are more driven by the rewarding aspects of smoking.

The prevalence of tobacco use and dependence among adolescents—as well as the neurobiological impact and medical consequences of nicotine exposure—suggest that pediatric primary care settings should deliver tobacco cessation treatments to both youth and parents who use tobacco.¹⁶⁹ Current clinical guidance does not recommend medications for adolescent tobacco cessation because of a lack of high-quality studies;¹⁷⁰ however, a combination of behavioral treatments—such as motivational enhancement and CBT—has shown promise for helping adolescents quit tobacco.¹⁷¹ More well-designed smoking cessation studies need to be conducted with adolescent smokers, particularly in the area of pharmacologic treatments for nicotine dependence.¹⁷⁰

Behavioral Treatments

Behavioral counseling is typically provided by specialists in smoking cessation for four to eight sessions.⁴⁰ Both in-person and telephone counseling have been found beneficial for patients who are also using cessation medications.¹⁶⁴ A variety of approaches to smoking cessation counseling are available.

Cognitive Behavioral Therapy (CBT)—CBT helps patients identify triggers—the people, places, and things that spur behavior—and teaches them relapse-prevention skills (e.g., relaxation techniques) and effective coping strategies to avoid smoking in the face of stressful situations and triggers.^172,173 A study that compared CBT and basic health education observed that both interventions reduced nicotine dependence.¹⁷⁴ However, another study found that among smokers trying to quit with the nicotine replacement therapy (NRT) patch, patients who participated in six sessions of intensive group CBT had better quit rates than those who received six sessions of general health education.¹⁷⁵

Motivational Interviewing (MI)—In MI, counselors help patients explore and resolve their ambivalence about quitting smoking and enhance their motivation to make healthy changes. MI is patient-focused and nonconfrontational, and providers point out discrepancies between patients’ goals or values and their current behaviors. They adjust to patients’ resistance to change and support self-efficacy and optimism.¹⁷³ Studies of MI suggest that this intervention results in higher quit rates than brief advice to stop smoking or usual care.¹⁷⁶

Mindfulness—In mindfulness-based smoking cessation treatments, patients learn to increase awareness of and detachment from sensations, thoughts, and cravings that may lead to relapse.¹⁷⁷ In this therapy, patients purposely attend to the thoughts that trigger cravings and urges for tobacco and cognitively reframe them as expected and tolerable. Patients learn techniques that help them tolerate negative emotions—including stress and cravings—without returning to tobacco use or other unhealthy behaviors.¹⁷⁷ Interest in mindfulness-based treatments has increased during the past decade, and studies show that this approach benefits overall mental health and can help prevent relapse to smoking.¹⁷⁸ However, well-controlled clinical trials are needed.

Telephone support and quitlines—As part of tobacco control efforts, all states offer toll-free telephone numbers (or quitlines) with smoking cessation counselors who provide information and support (800-QUIT-NOW or 800-784-8669). Studies of quitline interventions indicate that smokers who call quitlines benefit from these services,¹⁷⁹ particularly when a counselor calls them back for multiple sessions.¹⁸⁰ There is limited evidence on the optimal number of calls needed, but smokers who participated in three or more calls had a greater likelihood of quitting, compared with those who only received educational materials, brief advice, or pharmacotherapy alone.¹⁸⁰ Quitlines have also been shown to help smokeless tobacco cessation.¹⁸¹ The U.S. Department of Health and Human Services provides a Smoking Quitline (877-44U-QUIT or 877-448-7848), as well as more information and tools for quitting (including text messages and other telephone-based support) at https://smokefree.gov/.

Text messaging, web-based services, and social media support—Technology, including mobile phones, internet, and social media platforms can be used to provide smoking cessation interventions. These technologies have the power to increase access to care by extending the work of counselors and overcoming the geographical barriers that may deter people from entering treatment.

A review of the literature on technology-based smoking cessation interventions (internet, personal computer, and mobile telephone) found that these supports can increase the likelihood of adults quitting, compared with no intervention or self-help information, and they can be a cost-effective adjunct to other treatments.¹⁸² A technology does not necessarily have to be recent or highly sophisticated to help boost cessation rates. For example, studies suggest that adults who receive encouragement, advice, and quitting tips via text-message—a capability on even the most basic mobile devices—show improved quit rates compared with control programs.^183,184

Among adult tobacco users who called a state quitline, most selected an integrated phone/web cessation program in favor of a web-only intervention.¹⁸⁵ Participants who chose the web-only option tended to be younger and healthier smokers, with a higher socioeconomic status. These participants tended to interact intensely with the site once, but did not re-engage as much as those who opted for the phone/web combination. A review of internet-based smoking cessation programs for adults suggested that interactive internet-based interventions that are tailored to individual needs can help people quit for 6 months or longer.^186,187 Future research should determine the effectiveness of different technologies for smoking cessation support among populations that may be hard to reach, including those of low socioeconomic status and adults older than age 50.

Technology-based cessation interventions are particularly relevant to young adults aged 18 to 25—about 3.2 million of whom smoked daily in 2016.⁷ A systematic review and meta-analysis of published randomized trials of technology-based interventions—including computer programs, internet, telephone, and text messaging—for smoking cessation among this population found that they increased abstinence by 1.5 times that of comparison subjects.¹⁸⁸ Researchers recommend embedding cessation interventions in commonly used social networking platforms,¹⁸⁹ and there has been some exploratory work in this area. Results of a trial with a relatively small number of participants suggested that Facebook was an accessible, low-cost platform for engaging young adults considering cessation. However, the study pointed to challenges in maintaining participation, retaining young people in the program, and the need for gender-specific features.¹⁸⁹ A randomized controlled trial has been designed to test a stage-based smoking cessation intervention on Facebook tailored for smokers aged 18 to 25. Participants will be recruited online, randomly assigned to a Facebook group according to their readiness to quit, and will receive tailored daily messages and weekly counseling. The study will assess the intervention’s impact on abstinence from smoking 3, 6, and 12 months after treatment, number of cigarettes smoked, quit attempts lasting 24 hours or more, and commitment to abstinence.¹⁹⁰

Medications

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Nicotine Replacement Therapy (NRT)—A variety of formulations of nicotine NRTs are available over the counter—including the transdermal patch, spray, gum, and lozenges—and are equally effective for cessation.^{37,38,197,198} NRTs stimulate the brain receptors targeted by nicotine, helping relieve nicotine withdrawal symptoms and cravings that lead to relapse.³⁷ Many people use NRT to help them get through the early stages of cessation, and those with more severe nicotine addiction can benefit from longer-term treatment. Use of NRT improves smoking cessation outcomes, and adding behavioral therapies further increases quit rates.¹⁹⁸ A combination of continual nicotine delivery through the transdermal patch and one other form of nicotine taken as needed (e.g., lozenge, gum, nasal spray, inhaler) has been found to be more effective at relieving withdrawal symptoms and cravings than a single type of NRT.^37,167,198 Researchers estimate that NRT increases quit rates by 50 to 70 percent.³⁷ Using the patch for up to 24 weeks has been shown to be safe.³⁹

Bupropion—Bupropion (immediate-release and extended-release) was originally approved as an antidepressant. It works by inhibiting the reuptake of the brain chemicals norepinephrine and dopamine as well as stimulating their release. Bupropion has been found to increase quit rates compared with placebo in both short- and long-term follow-up studies^166,198,199 and is indicated for smoking cessation. It is equally effective to NRT.¹⁶⁷

Varenicline—Varenicline helps reduce nicotine cravings by stimulating the alpha-4 beta-2 nicotinic receptor but to a lesser degree than nicotine. Varenicline boosts the odds of successfully quitting, compared with unassisted attempts.¹⁹⁸ Varenicline increased the likelihood of quitting compared with placebo, and some studies find that it is more effective than single forms of NRT^200,201 and bupropion.¹⁶⁷ In a primary care setting, 44 percent of patients on varenicline, either alone or combined with counseling, were abstinent at the 2-year follow-up. Patients who participated in group therapy and adhered to the medication were more likely to remain abstinent.²⁰² Research also suggests that this medication may be more effective than bupropion.¹⁹⁹

Medication combinations—Some studies suggest that combining NRT with other medications may facilitate cessation. For example, a meta-analysis found that a combination of varenicline and NRT (especially, providing a nicotine patch prior to cessation) was more effective than varenicline alone.²⁰³ Similarly, adding bupropion to NRT also improved cessation rates.¹⁹⁹ For smokers who could not cut down significantly by using the NRT patch, combining extended-release bupropion and varenicline was more effective than placebo, particularly for men and those who were severely nicotine dependent.¹³⁹

Other antidepressants—In addition to bupropion, some other antidepressant medications have also been found effective for smoking cessation, independent of their antidepressant effects, and are considered second-line treatments. A few small studies suggest that nortriptyline is equally effective as NRT.^167,199 Although nortriptyline may have side effects in some patients, the small studies for its use in smoking cessation have not reported any.¹⁹⁹ Researchers have not observed any impact of selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine, and sertraline) on smoking, either alone or in combination with NRT.¹⁹⁹

Precision Medicine—Researchers have been examining ways to personalize treatment based on important individual biological differences, including genetic differences. The field of pharmacogenetics examines how genes influence therapeutic response to medications, providing critical information to help tailor pharmacotherapies to the individual for maximum benefit. For example, people metabolize nicotine at different rates because of variations in several genes. Individuals who metabolize nicotine quickly smoke more, show greater dependence, and have more difficulty quitting.²⁰⁴ Such genetic variation influences the therapeutic responses to NRT and other cessation medications.^204,205 A recent study compared rates of abstinence 1 week after treatment for slow, normal, and fast metabolizers of nicotine who were randomly assigned to either placebo, NRT, or varenicline. Results indicated that varenicline worked best for normal nicotine metabolizers, whereas NRT patches were most effective for slow metabolizers.^205,206

Promising medications and ongoing research—NIDA supports research to develop new and improve current treatment options for smoking cessation based on a growing understanding of the neurobiology of addiction. In the area of medications, research is focusing on the receptors targeted by nicotine and the brain circuits and regions known to influence nicotine consumption.²⁰⁸ Newer brain targets—including the orexin and glutamate signaling systems—have also shown promise for medication treatment.^207,208 Repurposing medications already on the market for other indications may also prove useful in the search for new smoking cessation therapies.^209,210 This approach has been successful in the past, as bupropion was an established antidepressant before the FDA approved it as a smoking cessation medication. One current candidate is N-acetylcysteine, a medication for acetaminophen overdose, which has shown promise as a treatment for various substance use disorders—including nicotine dependence.²¹¹ Another approach that could prevent relapse and that has shown promise in early studies is a nicotine vaccine, which would generate antibodies that keep nicotine from reaching the brain.^212,213

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a relatively new approach being tested to treat addiction. It is a physiological intervention that noninvasively stimulates neural activity in targeted areas of the brain using magnetic fields. Multiple TMS pulses given consecutively are referred to as repetitive TMS (rTMS). The FDA has approved two rTMS devices for depression treatment in adults.

Research on rTMS as a treatment for smoking cessation is in early stages but has shown promise.^214,215 Among adult smokers who had not been able to quit using other treatments, high-frequency TMS treatment significantly reduced the number of cigarettes smoked. Combining high-frequency TMS with exposure to smoking cues improved effectiveness and boosted the overall abstinence rate to 44 percent at the end of the treatment. Six months after treatment, 33 percent of participants remained abstinent from cigarettes.²¹⁶ Future randomized controlled clinical trials with large numbers of patients will be needed to establish its efficacy for smoking cessation.