Tobacco use is “the leading cause of preventable disease, disability, and death in the United States.”1 Nearly 40 million US adults smoke cigarettes, and approximately 4.7 million middle and high school students use >1 tobacco product, including e-cigarettes.1 Cigarette smoking is a “major modifiable health risk factor,” but smoking cessation is difficult and the average smoker attempts to quit 5 times before achieving permanent success.2 

Successful smoking cessation involves a 2-pronged approach, since there are 2 components to smoking – physiological and behavioral, according to Nervana Elkhadragy, PharmD, MS, TTS, of Purdue University, College of Pharmacy, Indianapolis.

“We treat both together – the physiological addiction and the behavioral habits associated with smoking,” she told MPR.

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Smoking Cessation Framework

Discussing smoking cessation with patients can be challenging, leading to frustration in many practitioners.3 To help guide the conversation, the USPSTF, American Academy of Family Physicians, and other societies recommend the “Five A’s” (Ask, Advise, Assess, Assist, and Arrange) as a framework for working with patients regarding smoking cessation.

Addressing Physiological Addiction with Pharmacotherapy

There are 7 US Food and Drug Administration (FDA)-approved medications for treating nicotine addiction; 5 are formulations of nicotine replacement therapy (NRT), and take the form of gum, lozenge, transdermal patch, nasal spray, and oral inhaler. Two additional medications are varenicline (a nicotinic receptor partial agonist) and bupropion (an antidepressant).4

“The choice of medication depends on multiple factors, which should be explored and discussed with the patient by the prescriber or pharmacist,” Dr Elkhadragy said.

For example, some NRT formulations (eg, gum, lozenges, nasal spray, and oral inhalers) need to be dosed frequently, which may compromise adherence. In contrast, bupropion and varenicline require only twice-daily dosing, and the NRT transdermal patch requires only once-daily dosing. On the other hand, some patients may prefer the oral experience of chewing gum or sucking a lozenge.

NRT agents can be used in combination, Dr Elkhadragy noted. “For example, a person can use the nicotine patch, which has one-daily dosing, but may need extra help in certain situations that are particularly triggering. Let’s say the person has always smoked during the morning drive to work, I might additionally recommend chewing gum during that drive.”

 She cautioned that smoking increases certain enzymes, such as cytochrome P1A2 (CYP1A2), thus, upon quitting, enzyme levels are normalized. Medications metabolized by CYP1A2 enzymes (eg, clozapine, olanzapine, duloxetine, mirtazapine) might require lower dosing, due to decreased enzyme production.5

Similarly, caffeine is broken down by the CYP1A2 enzyme, “so smokers tend to drink more caffeine than other people – for example, they may drink 4 cups of coffee, which would be equivalent to 2 cups of coffee in someone else,” Dr Elkhadragy said. But when they quit smoking, the enzyme is reduced and if they continue to drink 4 cups of coffee, they are at risk of caffeine toxicity. 

This is especially problematic because caffeine toxicity can be confused with nicotine withdrawal as some of the symptoms such as irritability, insomnia, and anxiety are common to both. “Patients may attribute their misery to nicotine withdrawal, assume their medication isn’t working, and may start smoking again,” she said.

She encouraged physicians and pharmacists to “ask patients about their use of caffeine and encourage smokers who are quitting to halve their caffeine intake.”

Talking to Patients about Smoking Cessation

Asking patients about their smoking habits and motivating them to quit involves empathetic, nonconfrontational, and nonjudgmental communication.2,6 

Motivational interventions “explore a patient’s ambivalence to smoking cessation in an empathetic, questioning manner, which respects the patient’s autonomy and builds self-efficacy.”2 The AAFP recommends the “5 R’s” (Relevance, Risks, Rewards, Roadblocks, and Repeat) as components of a discussion to “enhance patients’ motivation to stop smoking.”2 

Planning and Timing 

The decision to quit smoking does not typically take place from one moment to the next but a process that tends to take place in stages. “One of the reasons so many quit attempts end in failure is that patients do not adequately plan ahead,” Robin Corelli, PharmD, Professor from the University of California, San Francisco, School of Pharmacy, told MPR

Every visit can be an opportunity to ask patients about their intentions to quit smoking and to discuss plans to make this happen. “The patient should set a quit date, ideally within the next several weeks, because you want to capitalize on the fact that they have made the decision and to act while that decision is fresh,” she advised.

Some patients pick a special day (eg, a birthday) to quit. But “I encourage patients to see the quit date itself as a ‘special day’ and I reach out on that date to congratulate them,” she recounted.

For other patients, quitting on a birthday might be difficult and they prefer a more routine date. Quitting when there is intense work pressure or during the holidays, might likewise be difficult.

“The decision of when to quit is a highly personal one,” she said. She encourages patients to “enlist support from friends, family, and coworkers, informing them of the quit date so that when times are challenging, the patient can tap into these individuals for assistance.”

She recommends that patients document smoking habits in a log for 3 to 5 days prior to their quit date, recording what time they smoked, what they were doing, and why they felt they needed or wanted a cigarette.

“Patients might discover that they were bored, or around another smoker, or they needed to get away from their desk at work so they took a ‘smoking break.’ This process enables introspection about smoking patterns, routines, and triggers which can inform the development of potential coping strategies prior to the quit date.” 

Dr Corelli also advises patients to get coaching when they are trying to quit. “The advantage of living in the US is that there is ready access to smoking cessation counselors at no cost through the national telephone quitline (1-800-QUIT-NOW [1800-784-8669]). This service, which is staffed by highly-trained specialists, helps callers develop personalized quit plans to manage challenges tied to particular tobacco use habits and routines.”

Nonpharmacologic Approaches

Behavioral interventions, alone or in combination with pharmacotherapy, improve achievement of tobacco cessation.7 These include physician- and nurse-delivered counseling, tailored self-help counseling materials, and telephone counseling.8

A burgeoning number of technologies are being used to augment smoking cessation counseling, including automatic voice recognition, in which a human voice delivers smoking cessation messages via telephone several times daily.9 Reliable apps recommended by the US Department of Health and Human Services (HHS) are available here.

The Promises and Pitfalls of Electronic Cigarettes

E-cigarettes “have become popular nicotine-delivery devices,” with as many as 4.5% of US adults (or 10.8 million people) reporting use in 2015.11 Of these, nearly half also used combustible cigarettes.11

“We know that even though many people try vaping as part of an approach to quit smoking [combustible cigarettes], the most frequent outcome is that they become dual users, sometimes vaping and sometimes smoking combustible cigarettes,” according to Marc Steinberg, PhD, Associate Professor of Psychiatry, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.

When this happens, “people often wind up taking more nicotine than before and becoming even more dependent,” he told MPR

There is a widely held perception that e-cigarettes are “safer than combustible cigarettes” and their use “can help smokers quit combustible cigarettes,” however the evidence for this is conflicting and controversial.11

Moreover, the appealing flavors, lack of lingering odor, and perception of reduced stigma may make these products more appealing in many age groups, but especially among youth, a population in which use of combustible cigarettes has been declining.11 One survey found that among middle and high school students, >5 million were current users of e-cigarettes and vaping products, and almost 1 million were using them daily in 2019.12 

Despite the allure and reasons that many people turn to e-cigarettes from combustible cigarettes, most adult users do want to quit using e-cigarettes,13 Dr Steinberg noted.

Youngsters, however, are less likely to be interested in discontinuing use of e-cigarettes and vaping. There is scant guidance on how healthcare professionals can actually help these young patients seeking to quit vaping.14 

One important talking point is the high risk of vaping-associated lung injury (EVALI), a serious respiratory illness that claimed the lives of 55 individuals as of December 27, 2019. At that time, 2561 cases of EVALI had been reported to the CDC. While most of hospitalized users (80%) reported using tetrahydrocannabinol (THC)-containing products, 54% reported use of nicotine-containing products, and 40% reported use of both.15 

Dr Corelli said that although the overall behavioral approaches to smoking cessation are similar when counseling individuals who are vaping and those who are using combustible cigarettes, there are unique pharmacologic challenges in dosing. “One of the problems is that there is no regulation of what goes into e-cigarettes, such as the liquids used in pen and tank model units,” she said. 

Because of the regulation of combustible cigarettes, it is easier to estimate the dose of nicotine a smoker is getting from each cigarette. That is not the case with e-cigarettes and vaping products. 

Further clouding the issue is the fact that e-cigarette liquids are commonly mislabeled. For example, the label may state that there is 10mg nicotine/mL, but the measured concentrations can be as high as 100mg/mL. 

“I am comfortable helping adults who are vaping and were former [combustible cigarette] smokers because they were accustomed to getting a certain dose of nicotine from their combustible cigarettes. For example, a pack a day smoker is likely to be getting a similar amount of nicotine from their vaping to replace what they had originally been receiving from smoking,” she said.

If this patient wanted to use NRT as a vaping cessation strategy, she would dose the selected NRT product for an individual smoking a pack a day. 

Dr Corelli described helping youth to quit using e-cigarettes and vaping as “an ongoing dilemma.” It is important to work with the teenager’s parents as much as possible, she said.

In the meantime, Dr Corelli said, clinicians can adapt approaches used for combustible cigarettes to e-products while research and more formal guidance continue to emerge.


 1.     Centers for Disease Control and Prevention (CDC). Smoking and tobacco use: data and statistics. (2019) Available at: Accessed: December 25, 2019.

2.     Larzelere MM, Williams DE. Promoting smoking cessation. Am Fam Physician. 2012 Mar 15;85(6):591-8.

3.     van Eerd EAM, Bech Risør M, Spigt M, Godycki-Cwirko, Andreeva E, Francis N, et al. Why do physicians lack engagement with smoking cessation treatment in their COPD patients? A multinational qualitative study. NPJ Prim Care Respir Med. 2017 Jun 23;27(1):41.

4.     American Academy of Family Physicians (AAFP). Pharmacologic Product Guide: FDA-Approved Medications for Smoking Cessation. Available at: Accessed: December 11, 2019.

5.     Maideen NMP. Tobacco smoking and its drug interactions with comedications involving CYP and UGT enzymes and nicotine. World J Pharmacol. 2019 Jan 30;8(2):14-25.

6.     Simmons VN, Litvin EB, Patel RD, et al. Patient-provider communication and perspectives on smoking cessation and relapse in the oncology setting. Patient Educ Couns. 2009;77(3):398-403. doi:10.1016/j.pec.2009.09.024

7.     Siu AL; U.S. Preventive Services Task Force. Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015 Oct 20;163(8):622-34.

8.     Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Oct 20;163(8):608-21.

9.     Mahoney MC, Erwin DO, Twarozek AM, et al. Leveraging technology to promote smoking cessation in urban and rural primary care medical offices. Prev Med. 2018;114:102–106.

10. Morriscey C, Shephard  A, van Houdt A, Kerr D, Barrett SP. Using ‘Smart’ Technology to Aid in Cigarette Smoking Cessation: Examining an Innovative Way to Monitor and Improve Quit Attempt Outcomes. J Smoking Cess. 2019;14(3):149-154.

11. Bhatnagar A, Payne TJ, Robertson RM. Is There A Role for Electronic Cigarettes in Tobacco Cessation? J Am Heart Assoc. 2019;8(12):e012742.

12. US Food and Drug Administration (FDA). Vaporizers, E-Cigarettes, and other Electronic Nicotine Delivery Systems (ENDS). Available at: Accessed: December 22, 2019.

13. Rosen RL, Steinberg M. Interest in Quitting E-Cigarettes among Adults in the United States. Nicotine Tob Res. 2019 Apr 23. [Epub ahead of print]

14. Foley KA. Doctors are prescribing off-label nicotine replacements for teens addicted to vaping. Quartz. October 3, 2019. Available at Accessed: December 15, 2019.

15.  Centers for Disease Control and Prevention (CDC). Outbreak of Lung Injury Associated with E-Cigarette, or Vaping, Products. Available at: Accessed: January 9, 2020.

This article originally appeared on MPR