National Cancer Institute

Cigarette smoking: Health Risks and How to Quit explains how smoking avoidance and cessation result in decreased incidence and mortality from cancer. Quit counseling and physician advice improve cessation rates. Get detailed information about smoking risks and quitting in this clinician summary.

Cigarette smoking: Health Risks and How to Quit explains how smoking avoidance and cessation result in decreased incidence and mortality from cancer. Quit counseling and physician advice improve cessation rates. Get detailed information about smoking risks and quitting in this clinician summary.

Cigarette Smoking: Health Risks and How to Quit


Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.

A separate PDQ summary on Levels of Evidence for Cancer Screening and Prevention Studies is also available.

The cancer prevention summaries in PDQ refer to cancer prevention, defined as a reduction in the incidence of cancer. The PDQ includes summaries generally classified by histological type of cancer, especially when there are known risk factors for the specific types of cancer. This summary addresses a specific risk factor, tobacco use, which is associated with a large number of different cancers (and other chronic diseases) and unequivocally contains human carcinogens. The focus of this summary is on clinical interventions by health professionals that decrease the use of tobacco.

Effects of Smoking Cessation

Based on solid evidence, cigarette smoking causes cancers of the lung, oral cavity and pharynx, larynx, esophagus, bladder, kidney, pancreas, stomach, uterine cervix, and acute myeloid leukemia. Smoking avoidance and smoking cessation result in decreased incidence and mortality from cancer.

  • Study Design: Evidence obtained from a randomized controlled trial (RCT).
  • Internal Validity: Good.
  • Consistency: Good.
  • Magnitude of Effects on Health Outcomes: The relative risk (RR) of several cancers is much greater in cigarette smokers compared with nonsmokers (depending on the anatomical site of the cancer and the intensity and duration of smoking, the RR can range from twofold to tenfold or greater in smoking populations). A reduction of 15% is seen in the RR of all-cause mortality in heavy smokers subjected to intensive clinical cessation interventions.
  • External Validity: Good.

Counseling and Smoking Cessation

Based on solid evidence, counseling by a health professional improves smoking cessation rates.

  • Study Design: Evidence obtained from RCTs.
  • Internal Validity: Good.
  • Consistency: Good.
  • Magnitude of Effects on Health Outcomes: Counseling improves cessation rates (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.32–1.84).
  • External Validity: Good.

Physician Advice and Smoking Cessation

Based on solid evidence, simple advice from a physician to stop smoking improves smoking cessation rates.

  • Study Design: Evidence obtained from RCTs.
  • Internal Validity: Good.
  • Consistency: Good.
  • Magnitude of Effects on Health Outcomes: Physician advice improves cessation rates (RR, 1.66; 95% CI, 1.42–1.94).
  • External Validity: Good.

Drug Treatment and Smoking Cessation

Based on solid evidence, drug treatments, including nicotine replacement therapies (gum, patch, spray, lozenge, and inhaler), selected antidepressant therapies (e.g., bupropion), and nicotinic receptor agonist therapy (varenicline), result in better smoking cessation rates than placebo.

  • Study Design: Evidence obtained from RCTs.
  • Internal Validity: Good.
  • Consistency: Good.
  • Magnitude of Effects on Health Outcomes: Nicotine replacement therapy treatments, alone or in combination, improve cessation rates over placebo after 6 months (RR, 1.55; 95% CI, 1.49–1.61). Treatment with bupropion improves cessation rates over placebo after 6 months (OR, 1.94; 95% CI, 1.72–2.19; RR, 1.60; 95% CI, 1.49–1.72). Varenicline therapy treatment improves cessation rates over placebo after 6 months (RR, 2.32; 95% CI, 2.15–2.51).
  • External Validity: Good.


  1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 83: 1-1438, 2004.
  2. The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Also available online. Last accessed March 28, 2024.
  3. Lancaster T, Stead L: Physician advice for smoking cessation. Cochrane Database Syst Rev (4): CD000165, 2004.
  4. Lemmens V, Oenema A, Knut IK, et al.: Effectiveness of smoking cessation interventions among adults: a systematic review of reviews. Eur J Cancer Prev 17 (6): 535-44, 2008.
  5. Hartmann-Boyce J, Chepkin SC, Ye W, et al.: Nicotine replacement therapy versus control for smoking cessation. Cochrane Database Syst Rev 5 (5): CD000146, 2018.
  6. Hajizadeh A, Howes S, Theodoulou A, et al.: Antidepressants for smoking cessation. Cochrane Database Syst Rev 5 (5): CD000031, 2023.
  7. Livingstone-Banks J, Fanshawe TR, Thomas KH, et al.: Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 5 (5): CD006103, 2023.

Evidence of Benefit


In the United States, smoking-related illnesses accounted for an estimated 480,000 deaths each year. (Also available online.) On average, these deaths occur 12 years earlier than would be expected, so the aggregate annual loss exceeds 5 million life-years. These deaths are primarily due to smoking’s role as a major cause of cancer, cardiovascular diseases, and chronic lung diseases. The known adverse health effects also include other respiratory diseases and symptoms, nuclear cataract, hip fractures, reduced female fertility, and diminished health status. Maternal smoking during pregnancy is associated with fetal growth restriction, low birth weight, and complications of pregnancy. About 30% of cancer deaths in the United States are attributable to smoking.

Tobacco products are the single, major avoidable cause of cancer, causing more than 155,000 deaths among smokers in the United States annually due to various cancers. The majority of cancers of the lung, trachea, bronchus, larynx, pharynx, oral cavity, nasal cavity, and esophagus are attributable to tobacco products, particularly cigarettes. Smoking is also causally associated with cancers of the pancreas, kidney, bladder, stomach, and cervix and with myeloid leukemia.

Smoking also has substantial effects on the health of nonsmokers. Environmental or secondhand tobacco smoke is implicated in causing lung cancer and coronary heart disease. Among children, secondhand smoke exposure is causally associated with sudden infant death syndrome, lower respiratory tract illnesses, otitis media, middle ear effusion, exacerbated asthma, and respiratory effects such as cough, wheeze, and dyspnea.

Environmental tobacco smoke has the same components as inhaled mainstream smoke, although in lower absolute concentrations, between 1% and 10%, depending on the constituent. Carcinogenic compounds in tobacco smoke include the polycyclic aromatic hydrocarbons (PAHs), including the carcinogen benzo[a]pyrene (BaP) and the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Elevated biomarkers of tobacco exposure, including urinary cotinine, tobacco-related carcinogen metabolites, and carcinogen-protein adducts, are seen in passive or secondhand smokers.

In 2014, 18.8% of adult men and 14.8% of adult women in the United States were current smokers. (Also available online.) Cigarette smoking is particularly common among American Indian and Alaska Native individuals. The prevalence of smoking also varies inversely with education, and was highest among adults who had earned a General Educational Development diploma (43.0%) and generally decreased with increasing years of education. (Also available online.) From 2011 to 2014, significant declines occurred in the use of cigarettes among middle school (4.3% to 2.5%) and high school (15.8% to 9.2%) students. Cigarette smoking prevalence among male and female high school students increased substantially during the 1990s in all ethnic groups with rates between 20% and 30%, but by 2022, it had declined to 2%. (Also available online.)

The effect of tobacco use on population-level health outcomes is illustrated by the example of lung cancer mortality trends. Smoking by women increased between 1940 and the early 1960s, resulting in a greater than 600% increase in female lung cancer mortality since 1950. Lung cancer is now the leading cause of cancer death in women. In the last 30 years, prevalence of current cigarette use has generally decreased, though far more rapidly in men. Lung cancer mortality in men peaked in the 1980s, and has been declining since then; this decrease has occurred predominantly in squamous cell and small cell carcinomas, the histological types most strongly associated with smoking. Variations in lung cancer mortality rates by state also more or less parallel long-standing state-specific differences in tobacco use. Among men, the average annual age-adjusted lung cancer death rates from 2017 to 2021 were highest in Mississippi (64.3 per 100,000), where 22% of men in Mississippi were current smokers in 2021, and lowest in Utah (18.8 per 100,000), where only 8% of men smoked. Among women, lung cancer death rates were highest in Kentucky (43.8 per 100,000), where 21% of women were current smokers, and lowest in Utah (13.9 per 100,000), where only 6% of women smoked.

Tobacco Use Interventions

Many health risks related to tobacco smoking can be reduced by smoking cessation. Smokers who quit smoking before age 50 years have up to half the risk of dying within 15 years compared with people who continue to smoke, and the risk of dying is reduced substantially even among individuals who stop smoking after age 70 years. The risk of lung cancer is 30% to 50% lower than that of continuing smokers after 10 years of abstinence, and the risk of oral and esophageal cancer is halved within 5 years of cessation. Smokers who quit also lower their risk of cervical, gastric, and bladder cancer.

A number of approaches at the policy, legislative, and regulatory levels have been attempted to effect widespread reduction in or prevention of commencement of tobacco use. Various efforts at the community, state, and national level have been credited with reducing the prevalence of smoking over time. These efforts include, reducing minors’ access to tobacco products, disseminating effective school-based prevention curricula together with media strategies, raising the cost of tobacco products, using tobacco excise taxes to fund community-level interventions including mass media, providing proven quitting strategies through health care organizations, and adopting smoke-free laws and policies.

The Lung Health Study

In a randomized trial of heavy smokers, the long-term follow-up results demonstrated that compared with the nonintervention group (n = 1,964), those randomly assigned to a smoking cessation intervention (n = 3,923) experienced a 15% reduction in all-cause mortality rates (8.83 vs. 10.38 per 1,000 person-years; P = .03). The smoking cessation intervention consisted of a strong physician message plus 12 group sessions and nicotine gum administered during a 10-week period. Decreases in the risk of lung and other cancers, and coronary heart disease, cardiovascular disease, and respiratory disease contributed to the benefit in the group randomly assigned to the smoking cessation intervention.

School-based interventions

School-based interventions alone have not demonstrated long-term impact for smoking prevention. One of the highest-quality studies was a large, randomized trial in which children received a theory-based program that incorporated various social-influence approaches from grade 3 through grade 12, with no difference in smoking outcomes observed either at grade 12 or at 2 years after high school between school districts receiving the intervention and those in the control arm.

Minimum legal age of access to tobacco products

Raising the minimum legal age of access (MLA) to tobacco products is a tobacco control policy option that has gained momentum. Currently, the MLA set by the federal government is 18 years of age, but states and municipalities can raise the MLA to older ages. In 2015, Hawaii became the first state to raise the MLA to 21 years, and many municipalities, including Boston and New York City, have enacted MLA 21-years legislation. An Institute of Medicine report thoroughly evaluated public health implications of raising the MLA. In the absence of direct evidence on this topic, the report was based on a series of assumptions about the impact of raising the MLA on reducing and delaying initiation of smoking. These assumptions were entered into statistical models that forecast the impact of increasing the MLA on smoking prevalence and smoking-caused premature deaths during the 21st century. Even the results of the more conservative Cancer Intervention and Surveillance Modeling Network estimated that an increase of the MLA to 21 years in 2015 would avert 249,000 smoking-caused premature deaths in a hypothetical U.S. birth cohort by 2100.

Despite the strong hypothetical evidence of benefit implied by the Institute of Medicine report, the dearth of direct evidence on raising the MLA makes it challenging to discern the actual impact of raising the MLA in real-world settings. Needham, Massachusetts became the first U.S. municipality to raise the MLA to 21 years in April of 2005. To evaluate the impact of raising the MLA, researchers used a post-intervention only time series approach to compare area-level smoking prevalence among high school students in Needham with 16 surrounding municipalities that had a constant MLA of 18 years. The source of smoking prevalence data was a biennial survey administered to students in grades 9 through 12; data from 2006, 2008, 2010, and 2012 were presented. During this 6-year period, the decrease in prevalence of current smoking in Needham (7.4%) was only slightly larger than the 16 surrounding municipalities (6.3%). Numerous limitations weaken the evidence provided by this study, including the assessment of evidence only more than a year after the MLA 21 years was enacted; this is especially important in the Needham example because the MLA had been gradually increased to MLA 19 years in 2003 and MLA 20 years in 2004 and ignoring these previous MLA increases would bias the findings toward the null. The lack of high-quality direct evidence evaluating the public health impact of raising the MLA accentuates the future need for stronger direct evidence on this topic.

Community Intervention Trial for Smoking Cessation (COMMIT)

The Community Intervention Trial for Smoking Cessation (COMMIT) was a National Cancer Institute-funded large-scale study to assess a combination of community-based interventions designed to help smokers cease using tobacco. COMMIT involved 11 matched pairs of communities in North America, which were randomly assigned to an arm offering an active community-wide intervention or a control arm (no active intervention). The 4-year intervention included messaging through existing media channels, major community organizations, and social institutions capable of influencing smoking behavior in large groups of people. The interventions were implemented in each community through a local community board that provided oversight and management of COMMIT activities.

In COMMIT, there was no difference in the mean quit rate of heavy-smokers in the intervention communities (18.0%) compared with the control communities (18.7%). The difference in light-to-moderate smoker quit rates were statistically significant: averages of 30.6% and 27.5% for the intervention and control communities, respectively (P = .004). Although no significant differences in quit rates between the sexes were observed, less-educated light-to-moderate smokers were more responsive to the intervention than were college-educated smokers with a light-to-moderate habit.

Clinical interventions targeted at individuals have shown more promising results. A meta-analysis of randomized controlled trials (RCTs) shows that 6-month cessation rates are significantly improved with the use of nicotine replacement therapy (NRT) products compared with placebo or no intervention (relative risk [RR], 1.55; 95% confidence interval [CI], 1.49–1.61). The benefits of NRT product use have been consistently observed regardless of whether the product used was the patch, gum, nasal spray, inhaler, or lozenge. Smoking cessation counseling alone is also effective; even a brief intervention by a health care professional significantly increases the smoking cessation rate.

Promoting smoking cessation among cancer survivors is essential because the deleterious health effects of cigarette smoking may impact prognosis in both the short term and long term. In an RCT of a peer-delivered smoking cessation intervention among childhood cancer survivors, a significantly higher 12-month quit rate was observed in the intervention group (15% vs. 9%; P< .01).

Tobacco Cessation Guidelines

In 1996, the Agency for Health Care Policy and Research (AHCPR), now the Agency for Healthcare Research and Quality released a landmark set of clinical smoking-cessation guidelines for helping nicotine-dependent patients and health care providers. Now sponsored by the U.S. Public Health Service, the updated 2008 guidelines, "Treating Tobacco Use and Dependence" are available online. The broad elements of these guidelines are:

  1. Clinicians should document the tobacco-use status of every patient.
  2. Clinicians should assess the readiness to quit of patients who use tobacco and assist those who wish to quit in setting a quit date.
  3. Patients using tobacco should be provided with at least one of the effective brief cessation interventions that are available.
  4. In general, more intense interventions are more effective than less intense interventions in producing long-term tobacco abstinence, reflecting the dose-response relationship between the intervention and its outcome.
  5. One or more of the three treatment elements identified as being particularly effective should be included in smoking-cessation treatment:
    1. Social support from clinicians in the form of encouragement and assistance.
    2. Skills training/problem solving (cessation/abstinence techniques).
    3. Pharmacotherapy, such as nicotine-replacement (e.g., patches, gum).
  6. To be effective, health care systems must make institutional changes resulting in systematic identification of tobacco users and intervention with these patients at every visit.

For individual interventions, the guidelines suggest a model based on outcomes from six major clinical trials of physician-delivered smoking intervention conducted in the late 1980s: the ASK, ADVISE, ASSESS, ASSIST, and ARRANGE model. The physician provides a brief intervention that entails asking about smoking status at every visit, advising abstinence, assisting by setting a quit date, providing self-help materials and recommending use of NRT, and arranging for a follow-up visit. See below for brief and expanded intervention outlines. The recommendations also strongly support the value of referral to more intensive counseling.

  1. Ask
    • Screen for smoking status at every visit or admission.
  2. Advise
    • Minimal Advice: “As your physician, I must advise you that smoking is bad for your health, and it would be important for you to stop.”
    • Augmented Advice: “Because of your (__________) condition, it is particularly important for you to stop. If you stop now, (briefly educate patient about basic health benefits from quitting).”
  3. Assess
    • Minimal Assessment: Ask every tobacco user if he/she is willing to make a quit attempt at this time.
    • Augmented Assessment: Assess characteristics of smoking history and patterns.
      • Amount smoked.
      • Quit history.
  4. Assist/Counsel
    • Minimal Assistance: Provide self-help materials; assess interest in quitting; and assess interest in and appropriateness of pharmacological aids.
    • Augmented Assistance: Provide brief 5- to 7-minute patient-centered counseling.
  5. Arrange Follow-Up Support
    • Minimal Follow-Up Support: Arrange for single follow-up contact by visit or by telephone in about 2 weeks; provide referral to a smoking counselor or group.
    • Extended Follow-Up Support: Establish “quit smoking” contract with quit date. Arrange three or more follow-up contacts by visit or by telephone.

Pharmacotherapy for Smoking Cessation

Pharmacological agents have been used successfully to aid in the cessation of smoking in the general population. Since the original AHCPR guidelines were published in 1996, various nicotine replacement products have been approved for over-the-counter sale, and additional evidence of the effectiveness of therapies for smoking cessation has been published. Pharmacotherapy of smoking cessation, including NRTs (gum, patch, spray, lozenge, and inhaler) and non-nicotine medications (e.g., bupropion and varenicline), results in statistically significant increases in smoking cessation rates over those of a placebo.

There are a growing number of smoking cessation pharmacotherapies that have been shown to be efficacious in significantly increasing rates of smoking cessation. The choice of therapy should be individualized based on a number of factors, including past experience, patient and/or physician preference, and potential agent side effects. As more is learned about specific genetic variants that influence a smoker's response to smoking cessation pharmacotherapies—such as polymorphisms in genes encoding enzymes involved in nicotine metabolism—this information could eventually be integrated into smoking cessation treatment planning. Presently, the evidence is not yet sufficient to be integrated into clinical practice.

The following sections summarize available pharmacological interventions to assist in tobacco cessation. More comprehensive information is available from product package inserts.

Pharmacological interventions to assist in tobacco cessation

Nicotine replacement therapy

Nicotine replacement products are designed to aid in the withdrawal symptoms associated with nicotine. Several precautions are warranted before initiating therapy, but it should be noted that these precautions do not constitute absolute contraindications. In particular, special considerations are necessary in some patient groups (e.g., those with medical conditions such as arrhythmias, uncontrolled hypertension, esophagitis, peptic ulcer disease, insulin-treated diabetes, or asthma, pregnant or breast-feeding women, and adolescent smokers).

Based on a synthesis of the results of 133 randomized trials, researchers found that NRT treatments, alone or in combination, improved cessation rates over placebos after 6 months (RR, 1.55; 95% CI, 1.49–1.61) and that similar benefits of NRT product use were observed regardless of the product type (patch, gum, nasal spray, inhaler, or lozenge). When compared directly, the use of a single fast-acting NRT, such as nicotine lozenges or gum, or the nicotine patch results in similar 6-month cessation rates (RR, 0.90; 95% CI, 0.77–1.05). The results of an analysis, including 16 randomized trials, concluded that combining a fast-acting NRT with the nicotine patch resulted in higher 6-month cessation rates compared with the nicotine patch alone (RR, 1.27; 95% CI, 1.17–1.37). However, not all trials supported this conclusion.

Table 1. Nicotine Patches

Brand Dose Side Effects Comments
d = day; OTC = over the counter; Rx = prescription; wk = week.
RxHabitrol7–21 mg/d Erythema Use for 6–12 wk
OTC Nicoderm CQ 7–21 mg/d Pruritus Use for 6–12 wk
OTCNicotrol5–15 mg/d Burning at site Use for 14–20 wk
RxProStep 11–22 mg/d Local irritation Use for 6–12 wk

Current guidelines generally recommend 8 to 12 weeks of transdermal nicotine therapy, starting on the quit day. Findings from two randomized placebo-controlled trials of transdermal therapy were divergent in their findings as to whether extended therapy (22–24 weeks vs. 8 weeks) improves quit rates.

Table 2. Nicotine Polacrilex Gums

BrandDose Side Effects Comments
d = day; OTC = over the counter.
OTCNicorette18–24 mg/d Stomatitis, sore throat Max 30 pieces/d; decrease 1 piece every 4–7 d
OTCNicorette DS 36–48 mg/d Jaw ache Max 20 pieces/d; decrease 1 piece every 4–7 d

Table 3. Nicotine Lozenges

BrandDoseSide EffectsComments
d = day; h = hour; OTC = over the counter; wk = week.
OTCCommit40–80 mg/dLocal irritation (warmth and tingling)Use for 12 wk; max 20 pieces/d. Wk 1–6: 1–2 lozenges every 1–2 h; wk 7–9: 1 lozenge every 2–4 h; wk 10–12: 1 lozenge every 4–8 h

Table 4. Nicotine Inhalers

BrandDoseSide EffectsComments
Rx = prescription; wk = week.
RxNicotrol Inhaler Individualized Local irritation Use up to 24 wk

Table 5. Nicotine Nasal Sprays

BrandDose Side EffectsComments
d = day; mo = month; Rx = prescription.
RxNicotrol NS Max 40 mg/d Nasal irritation Max use 3 mo

Non-nicotine products

Bupropion HCl

Also used as an antidepressant, bupropion HCl is a non-nicotine aid to smoking cessation. It is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine, and does not inhibit monoamine oxidase. The exact mechanism by which bupropion HCl enhances the ability of patients to abstain from smoking is unknown; however, it is presumed that this action is mediated by noradrenergic or dopaminergic mechanisms. Based on the results of 50 randomized trials that compared the antidepressant, bupropion to placebo, after 6 months of follow-up, bupropion was associated with a statistically significant increase in the likelihood of quitting smoking (RR, 1.60; 95% CI, 1.49–1.72). While there was insufficient evidence to support the idea that combining bupropion plus NRT increases smoking cessation rates over those of NRT alone (RR, 1.17; 95% CI, 0.95–1.44), results (based on three trials) indicated that the combination of bupropion and varenicline may result in higher 6-month cessation rates compared with varenicline alone (RR, 1.21; 95% CI, 0.95–1.55). Although there was no difference in the efficacy of bupropion compared with single-form NRT (RR, 1.03; 95% CI, 0.93–1.13), there was evidence that the use of bupropion resulted in lower cessation rates than varenicline (RR, 0.73; 95% CI, 0.67–0.80) and combination NRT (RR, 0.74; 95% CI, 0.55–0.98), and higher cessation rates than the antidepressant, nortriptyline (RR, 1.30; 95% CI, 0.93–1.82).

Table 6. Bupropion Hydrochloride

BrandDoseSide EffectsWarning/Precaution
d = day; Rx = prescription; wk = week.
Rx Zyban 150 mg/d × 3 d then increase to 300 mg/d × 7–12 wkInsomnia, dry mouth, dizziness, rhinitis Do not take with Wellbutrin or Wellbutrin SR
Higher incidence of seizures in patients treated for bulimia, anorexia
Do not prescribe >300 mg/d for patients being treated for bulimia


Varenicline is a selective partial agonist at the alpha-4-beta-2 nicotinic acetylcholine receptor, which mediates nicotine dependence through dopamine release. Varenicline prevents nicotine from binding to the receptor and reduces both the rewarding effects of smoking and withdrawal symptoms. In two of the initial RCTs for smoking cessation, varenicline was titrated to a dose of 1 mg twice a day and compared with bupropion sustained-release (SR) 150 mg twice a day and a placebo group. Treatment lasted for 12 weeks, with an additional 40 weeks of posttreatment follow-up. In both studies, varenicline was more efficacious than bupropion and placebo for continuous abstinence from smoking at 9 to 12 weeks and at 9 to 24 weeks of follow-up. For 9 to 52 weeks of follow-up, varenicline was more efficacious than placebo in both studies. At 52 weeks of follow-up, the 7-day point prevalence of smoking abstinence was 46% higher in the varenicline group than in the bupropion SR group (odds ratio [OR], 1.46; 95% CI, 1.04–2.06). The other study also showed a 46% higher continuous abstinence in the varenicline group (OR, 1.46; 95% CI, 0.99–2.17). Approximately 30% of the participants who were randomly assigned to receive varenicline reported nausea, more than double that in the bupropion groups, and triple that seen in the placebo groups. In a randomized trial comparing varenicline with transdermal nicotine, continuous abstinence was greater in the varenicline group than in the transdermal nicotine group at the end of treatment (56% vs. 43%; P< .001) and during posttreatment follow-up (26% vs. 20%; P = .06). The prevalence of nausea in the varenicline group (37%) was more than triple that in the transdermal nicotine group (10%). However, this result was not confirmed in a subsequent randomized trial that compared varenicline with the nicotine patch. There was little difference in 7-day point-prevalence abstinence after 26 weeks (24% vs. 23%; P = .82) or 52 weeks (19% vs. 21%; P = .61) between those randomly assigned to the varenicline intervention and those assigned to the nicotine-patch intervention.

The results of a synthesis of 41 randomized trials indicated that varenicline results in increased 6-month cessation rates when compared with placebo (RR, 2.32; 95% CI, 2.15–2.51), bupropion (RR, 1.36; 95% CI, 1.25–1.49), and single-form NRT (RR, 1.25; 95% CI, 1.14–1.37), but provided no clear evidence that varenicline was superior to dual NRT (RR, 1.02; 95% CI, 0.87–1.20 ).

After a period of postmarketing surveillance, on July 1, 2009, the U.S. Food and Drug Administration (FDA) required additions to the Boxed Warnings for both bupropion and varenicline to describe the risk of serious neuropsychiatric symptoms associated with these products. Symptoms include: “changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.” The FDA further advised that the important health benefits of quitting smoking “should be weighed against the small, but real, risk of serious adverse events with the use of varenicline or bupropion.” Subsequently, the FDA required the manufacturers of bupropion and varenicline to conduct a clinical trial to evaluate the neuropsychiatric safety of these medications in patients with and without a history of psychiatric disorders (EAGLES trial). This randomized, double-blind, triple-dummy, placebo-controlled and active-controlled (nicotine patch) trial of varenicline and bupropion included over 8,000 cigarette smokers (one-half of which had current or a history of psychiatric disorders) from 140 sites in 16 countries. In the nonpsychiatric cohort, the varenicline-placebo and bupropion-placebo risk differences (RDs) for moderate and severe neuropsychiatric adverse events were -1.28 (95% CI, -2.40 to -0.15) and -0.08 (95% CI, -1.37 to 1.21), respectively. In the psychiatric cohort, the varenicline-placebo and bupropion-placebo RDs were 1.59 (95% CI, -0.42 to 3.59) and 1.78 (95% CI, -0.24 to 3.81), respectively. The most frequent adverse events by treatment group were nausea (varenicline, 25%), insomnia (bupropion, 12%), abnormal dreams (nicotine patch, 12%), and headache (placebo, 10%). The results of the trial did not show a significant increase in rates of moderate-to-severe neuropsychiatric adverse events with either varenicline or bupropion in those with or without psychiatric disorders and were supported by other studies analyzing data from multiple cessation trials. These results prompted the FDA to remove the Boxed Warnings for both bupropion and varenicline in 2016, noting that although the risk of mental health side effects is still present particularly for individuals with some mental illnesses, the “results of the trial confirm that the benefits of stopping smoking outweigh the risks of these medicines.”

A meta-analysis of double-blind, placebo-controlled, randomized trials of varenicline administered for at least 1 week (N = 14 trials) indicated that varenicline was associated with an increased risk of serious adverse cardiovascular events (RR, 1.72; 95% CI, 1.09–2.71). This finding is particularly noteworthy because almost all of the randomized trials included in the meta-analysis had the following in common: they excluded patients with cardiovascular disease (CVD) at baseline; the usual average age of the patient populations (early 40s) was young for CVD; varenicline was usually administered for only 12 weeks or less; and varenicline is efficacious for smoking cessation, which would act to decrease CVD risk. A subsequent extension study to the EAGLES trial, described above, evaluated the time to development of major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) across treatment groups (placebo, NRT, bupropion, and varenicline) as a primary outcome. The extension study reported no significant difference in time to onset of MACE for varenicline or bupropion compared with placebo (varenicline: hazard ratio [HR], 0.29; 95% CI, 0.05–1.68 and bupropion: HR, 0.50; 95% CI, 0.10–2.50) and no significant differences in the incidence of cardiovascular events during treatment by treatment group. An analysis of 18 studies reported that while more people taking varenicline experienced cardiac serious adverse events compared with placebo or no medication (RR, 1.20; 95% CI, 0.79–1.8), conclusions about harm are limited because of imprecision in the estimates.

Table 7. Varenicline

BrandDoseSide EffectsWarning/Precaution
d = day; Rx = prescription; wk = week.
RxChantix0.5 mg/d, d 1–3; 0.5 mg twice a d, d 4–7; then 1.0 mg twice a d through wk 12Nausea, insomniaRisk of toxicity greater in patients with impaired renal function
Not tested in children and pregnant women


Although Zyban (bupropion HCl) is the only antidepressant approved by the FDA for smoking cessation, Prozac (fluoxetine HCl) has been shown to be effective.

Table 8. Fluoxetine

BrandDose Side EffectsComments
d = day; Rx = prescription.
RxProzac 30–60 mg/d Insomnia, dizziness, anorexia, sexual dysfunction, confusion Limited data available on its use in combination with cognitive-behavioral therapy


Cytisine is a naturally occurring compound isolated more than 50 years ago from the plant Cytisus laburnum, a partial nicotinic acetylcholine receptor agonist. It has a long history of use for smoking cessation in Bulgaria and other eastern European nations, including clinical trials published in the 1970s. As this older evidence has been uncovered, it has led to more recent trials in western nations; a systematic review and meta-analysis showed clear benefit for cytisine compared with placebo. For all trials combined (n = 9 trials; 2,141 cytisine participants, 1,879 placebo participants), the pooled RR for abstinence from smoking at the longest follow-up for cytisine was 1.59 (95% CI, 1.43–1.75), compared with placebo. When the analyses were limited to two high-quality trials published since 2008, the pooled RR for smoking abstinence was 3.29 (95% CI, 1.84–5.90). There has been no evidence of serious adverse events, but gastrointestinal symptoms have been more common in the cytisine (12%) group compared with the placebo (7%) group.

A randomized trial in New Zealand compared cytisine (n = 655) with NRT (n = 655). Compared with the group who received NRT, the cytisine group had higher continued abstinence at 1 month (40% vs. 31%; RD, 9%; 95% CI, 4%–15%), 2 months (31% vs. 22%; RD, 9%; 95% CI, 4%–14%), and 6 months (22% vs. 15%; RD, 7%; 95% CI, 2%–11%). With respect to adverse events, there was no difference between groups for serious adverse events, but comparing the cytisine group with the NRT group, nausea and vomiting (28 events vs. 2 events) and sleep disorders (28 events vs. 2 events) were more common in the cytisine group. This trial is noteworthy because of the following results:

  1. It considerably strengthened an already substantial body of evidence indicating that cytisine is an efficacious smoking cessation pharmacotherapy.
  2. It showed that cytisine is more efficacious than NRT products that are known to be effective.

Table 9. Cytisine

BrandDoseSide EffectsComments
d = day; h = hour; mg = milligram; OTC = over the counter; Rx = prescription; wk = week.
Cytisine (Rx and OTC) Tabex, Desmoxan 1.5–9.0 mg/dNausea, vomiting, sleep disturbancesUse for 3–4 wk, d 1–3: 1 tablet every 2 h; d 4–12: 1 tablet every 2.5 h; d 13–16: 1 tablet every 3 h; d 17–20: 1 tablet every 4 h; d 21–25: 1 tablet every 6 h


Lobeline (Bantron) is classified as a category III agent by the FDA, safe but not proven effective. This product is not recommended for use in any smoking cessation program due to its lack of efficacy.

Other agents

Clonidine and nortriptyline have been suggested as possibly useful second-line pharmacotherapies but are not approved for smoking cessation by the FDA. Nortriptyline is an antidepressant that does not contain nicotine. A meta-analysis of five RCTs found that smokers who received nortriptyline were 2.4 times more likely (95% CI, 1.7–3.6) than smokers who received a placebo to remain abstinent from smoking after 6 months.

Smoking Reduction

Among smokers who are interested in quitting but not ready to make an immediate quit attempt, gradually decreasing the number of cigarettes smoked per day leading up to a quit attempt may prove to be a viable intervention strategy. This reduce to quit approach was tested in the context of an RCT. In this study, both the intervention group and control group received counseling with the goals of reducing the number of cigarettes smoked per day by 75% or greater by week 8 and to quit smoking entirely by week 12. The intervention group (n = 760) also received smoking cessation pharmacotherapy (varenicline at a maintenance dose of 1 mg bid for 24 weeks), whereas the control group (n = 750) received placebo tablets. For the primary end point of self-reported smoking abstinence during weeks 15 through 24, a statistically significant RD of 25.2% (varenicline group, 32.1% vs. placebo group, 6.9%; 95% CI, 21.4%–29.0%) was observed. The clinical significance of this finding is that it provides evidence of benefit for a pharmacotherapy-enhanced intervention aimed to motivate smokers who are interested in quitting, but not yet ready to quit, to start by cutting down on the number of cigarettes per day as a lead-in to a subsequent quit attempt.

For a smoker who wants to quit, an important practical question is whether a quit attempt is more likely to successfully result in smoking cessation if it involves abruptly stopping smoking or gradually decreasing the number of cigarettes smoked per day leading up to a quit attempt. U.S. evidence-based guidelines recommend abrupt quitting as the preferred approach, but guidelines from other countries vary on this matter. A systematic review of this topic revealed substantial heterogeneity in the results across studies, but the results showed that gradual cessation was associated with a 6% lower likelihood of smoking cessation than abrupt cessation that was not statistically significant (RR, 0.94; 95% CI, 0.79–1.13). To directly test this question, 697 smokers who wanted to quit were recruited from 31 primary care clinics in England, and randomly assigned to either a gradual or abrupt smoking cessation intervention. In this noninferiority trial, both groups were provided with access to NRT during the two weeks before the planned quit date. In the gradual cessation group, plans were made to cut down the number of cigarettes per day by 75% by the planned quit date; however, the abrupt cessation group was advised to follow usual smoking patterns until stopping smoking entirely on the planned quit date. Both groups were provided with NRT after the quit date and throughout the trial. For the primary end point of prolonged validated smoking abstinence at 4 weeks, the gradual cessation arm was less likely to quit smoking than the abrupt cessation arm (39.2% vs. 49.0%); a difference that was statistically significant (RD, -9.8%; 95% CI, 2.5%–17.1%). The statistically significantly lower likelihood of smoking cessation in the gradual versus abrupt intervention arms persisted during follow-up at 8 weeks (29.2% vs. 36.6%; RD, -7.4%; 95% CI, 0.4%–14.3%) and 6 months (15.5% vs. 22.0%; RD, -6.5%; 95% CI, 0.7%–12.2%). Baseline patient preferences for a gradual or abrupt quit attempt indicated that smokers who preferred the gradual quitting approach had a lower likelihood of smoking abstinence at 4 weeks (38% vs. 52%), suggesting that patient preferences for these methods may be a marker for other factors associated with successful quitting, such as motivation to quit. However, even when stratified by baseline patient preferences, the gradual cessation method resulted in lower likelihood of cessation both among those who preferred the gradual approach (34.6% vs. 42.0%) and those who preferred the abrupt approach (45.8% vs. 58.1%). The overall clinical significance of this study is that it provides evidence that in the setting of a pharmacotherapy-aided quit attempt among smokers interested in quitting, quitting abruptly is a more effective smoking cessation strategy than gradually cutting down on the number of cigarettes smoked before making a quit attempt; this holds true regardless of smoker preferences in methods. A quit attempt regardless of method should never be discouraged, but abrupt cessation appears to be the most effective strategy. In this context, abrupt cessation is distinct from making an unaided quit attempt (i.e., quitting “cold turkey”).

Among dependent smokers, complete abstinence from smoking is the ultimate goal. Even in instances when complete abstinence from smoking is not achieved, smoking cessation pharmacotherapies may benefit individual health—and ultimately the public’s health—if the smoker reduces the number of cigarettes smoked. The relationship between cigarette smoking and lung cancer, and other smoking-associated malignancies, is strongly dose-dependent. Thus, an individual smoker who is unable to achieve abstinence or who is not motivated to quit smoking may benefit by using pharmacotherapies (or other means) to reduce the number of cigarettes smoked per day. NRT has thus generated attention as a viable means of “harm reduction.” In studies that randomly assigned smokers who were not trying to quit to NRT or placebo, a greater proportion of those randomly assigned to NRT compared with placebo reduced the number of cigarettes per day. However, the impact of NRT on smoking reduction appears not to be sustained in the long run. Less evidence is available for bupropion, varenicline, and psychosocial interventions as a means of harm reduction. A potential problem with such a harm reduction strategy would be if it prevented cessation among smokers who would have otherwise quit smoking. Evidence shows that smoking reduction is actually associated with increased likelihood of future cessation. Another potential negative aspect of harm reduction would be if smokers reduced the number of cigarettes smoked per day but modified the way the cigarettes were smoked in such a way that exposure to tobacco toxins was not actually reduced (e.g., by inhaling more deeply). Compensatory behaviors such as inhaling more deeply or smoking more of a cigarette are attempts by the smoker to try to maintain nicotine levels, so the use of supplemental NRT presumably safeguards against this. Evidence from studies of smoking reduction with NRT that measured smoking biomarkers indicates that compensation occurs, but not to such an extent that it would be expected to outweigh the reduction in exposure from the reduced number of cigarettes per day.

Financial Incentive Programs for Smoking Cessation

Financial incentive programs can offer additional support for smoking cessation efforts. Results from a recent randomized trial suggest that the efficacy of such programs may be influenced greatly by the way rewards are disbursed.

The trial randomly assigned 2,538 participants to either one of four incentive programs or usual care. The four programs were combinations of scope (two programs targeted individuals, and two targeted groups of six participants) and incentive structure (one of the individual-focused programs and one of the group-focused programs provided rewards of approximately $800 to participants who achieved cessation at 6 months; the others required an initial refundable deposit of $150, supplemented with $650 in reward payments for successful cessation). The rationale for the four intervention arms was based on behavioral observations that 1) people are more loss averse than gain seeking and 2) collaboration/competition with others can bolster intervention efficacy.

Two main dimensions of the intervention effects were explored:

  1. Acceptance of the intervention.
  2. Efficacy of the intervention.

Both intent-to-treat and per-protocol analyses were performed, with an in-depth sensitivity analysis for potential biases accompanying the latter. In the intent-to-treat analyses (which evaluated the overall efficacy of the interventions), all of the financial incentive arms demonstrated significantly higher 6-month abstinence rates than did usual care (9.4%–16%, compared with 6% for usual care). The 6-month abstinence rates were similar between the group-focused and individual-focused arms (13.7% and 12.1%, respectively; P = .29), but the reward-based programs were associated with higher abstinence rates than were the deposit-based ones (15.7% vs. 10.2%; P< .001).

However, per-protocol analyses that accounted for the dramatically lower acceptance rate for the deposit-based interventions than for the reward-based interventions (14% vs. 90%) estimated that 6-month abstinence rates could be 13.2 percentage points (95% CI, 3.1–22.8) higher in the deposit-based programs than in the reward-based programs among the estimated 13.7% of participants who would participate in either type of program. That is, deposit-based interventions may be more efficacious than reward-based interventions but harder to get people to commit to.

A Changing Marketplace for Tobacco Products and Nicotine-Delivery Devices

The expansion in the marketplace of tobacco products and devices that deliver nicotine poses new challenges to tobacco control. Examples of nontraditional tobacco products in the U.S. market include small cigars, water pipe tobacco smoking (“hookah”), and new types of flavored, smokeless tobacco products modeled after Swedish snus. Prominent among non–tobacco-containing nicotine delivery devices are electronic cigarettes (or “e-cigarettes”) that have experienced a rapid upsurge in use and are now marketed by the major U.S. tobacco companies. Monitoring this expansion in products, how the products are used (e.g., product switching, multiple use, and use for tobacco cigarette smoking cessation), and the harms and benefits associated with their use compared with the use of tobacco cigarettes is critical to the development of more effective tobacco control strategies.

Research to determine the potential risks and benefits of these new products is just emerging, and initial findings are mixed. The potential benefits of e-cigarettes as a smoking cessation aid for adult smokers is further complicated by two additional factors. First, there has been a marked increase in the use of e-cigarettes by adolescents, with current (past 30-day) e-cigarette use by high school seniors rising dramatically over the last 3 years to 27.5% in 2019. Second, the product has evolved rapidly, with newer electronic nicotine delivery systems, such as JUUL, more quickly and effectively delivering nicotine to the lungs and more closely mimicking cigarettes in terms of their pharmacokinetics.

In one study, 886 adults who attended the U.K. National Health Service stop-smoking services were randomly assigned to either starter packs of nicotine replacement medication or e-cigarettes. At 1 year, biochemically confirmed abstinence was 18.0% in the e-cigarette group compared with 9.9% in the nicotine-replacement group (P< .001). However, at 1 year, 80% of abstinent e-cigarette users were still using e-cigarettes, compared with 9% of abstinent nicotine-replacement medication users still using their products. In contrast, a recent pragmatic trial randomly assigned smokers who were employed at 54 companies to access one of four interventions, which included usual care (information and motivational text messages), FDA-approved cessation medications, e-cigarettes, and financial incentives. The authors found that financial incentives added to free FDA-approved cessation medications resulted in higher quit rates than did cessation medications alone, and among smokers who received usual care, the addition of free cessation medications or e-cigarettes did not provide an added benefit.

Evidence suggests that cessation interventions delivered during children's pediatric visits to parents who smoked boost cessation rates. A recent cluster randomized clinical trial demonstrated higher quit rates 2 years after cessation interventions were delivered during pediatric visits, although there were a limited number of clusters (n = 10) included in the trial.


  1. Jamal A, Agaku IT, O'Connor E, et al.: Current cigarette smoking among adults--United States, 2005-2013. MMWR Morb Mortal Wkly Rep 63 (47): 1108-12, 2014.
  2. Nelson DE, Kirkendall RS, Lawton RL, et al.: Surveillance for smoking-attributable mortality and years of potential life lost, by state--United States, 1990. Mor Mortal Wkly Rep CDC Surveill Summ 43 (1): 1-8, 1994.
  3. The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Also available online. Last accessed March 28, 2024.
  4. American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. Available online. Last accessed January 17, 2024.
  5. Centers for Disease Control and Prevention: Targeting Tobacco Use: The Nation's Leading Cause of Death 2005. CDC, 2005.
  6. Ontario Task Force on the Primary Prevention of Cancer: Recommendations for the Primary Prevention of Cancer. Queen's Printer for Ontario, 1995.
  7. U.S. Department of Health and Human Services: The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006. Also available online. Last accessed December 19, 2023.
  8. Cinciripini PM, Hecht SS, Henningfield JE, et al.: Tobacco addiction: implications for treatment and cancer prevention. J Natl Cancer Inst 89 (24): 1852-67, 1997.
  9. Finette BA, O'Neill JP, Vacek PM, et al.: Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke. Nat Med 4 (10): 1144-51, 1998.
  10. Benowitz NL: Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 18 (2): 188-204, 1996.
  11. Hecht SS: Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Carcinogenesis 23 (6): 907-22, 2002.
  12. Jamal A, Homa DM, O'Connor E, et al.: Current cigarette smoking among adults - United States, 2005-2014. MMWR Morb Mortal Wkly Rep 64 (44): 1233-40, 2015.
  13. Youth and Tobacco Use. Atlanta, Ga: Centers for Disease Control and Prevention, 2015. Available online. Last accessed December 22, 2023.
  14. Jemal A, Thun MJ, Ries LA, et al.: Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 100 (23): 1672-94, 2008.
  15. Johnston LD, O'Malley PM, Bachman JG: Monitoring the Future: National Survey Results on Drug Use, 1975-2001. Volume I: Secondary School Students. National Institute on Drug Abuse, 2002. NIH Pub. No. 02-5106. Also available online. Last accessed December 15, 2023.
  16. U.S. Preventive Services Task Force: Guide to Clinical Preventive Services: Report of the U.S. Preventive Services Task Force. 2nd ed. Williams & Wilkins, 1996.
  17. American Cancer Society: Cancer Prevention & Early Detection Facts & Figures 2023-2024. American Cancer Society, 2024. Available online. Last accessed February 2, 2024.
  18. Schoenborn CA, Adams PF, Peregoy JA: Health behaviors of adults: United States, 2008-2010. Vital Health Stat 10 (257): 1-184, 2013.
  19. U.S. Department of Health and Human Services: The Health Benefits of Smoking Cessation. A Report of the Surgeon General. U.S. Department of Health and Human Services, 1990. DHHS Publ No. (CDC) 90-8416.
  20. Wingo PA, Ries LA, Giovino GA, et al.: Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking. J Natl Cancer Inst 91 (8): 675-90, 1999.
  21. Koh HK: The end of the "tobacco and cancer" century. J Natl Cancer Inst 91 (8): 660-1, 1999.
  22. Anthonisen NR, Skeans MA, Wise RA, et al.: The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med 142 (4): 233-9, 2005.
  23. Thomas R, Perera R: School-based programmes for preventing smoking. Cochrane Database Syst Rev 3: CD001293, 2006.
  24. Peterson AV, Kealey KA, Mann SL, et al.: Hutchinson Smoking Prevention Project: long-term randomized trial in school-based tobacco use prevention--results on smoking. J Natl Cancer Inst 92 (24): 1979-91, 2000.
  25. Bonnie RJ, Stratton K, Kwan LY, eds.: Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. The National Academies Press, 2015. Also available online. Last accessed December 22, 2023.
  26. Kessel Schneider S, Buka SL, Dash K, et al.: Community reductions in youth smoking after raising the minimum tobacco sales age to 21. Tob Control 25 (3): 355-9, 2016.
  27. Community Intervention Trial for Smoking Cessation (COMMIT): summary of design and intervention. COMMIT Research Group. J Natl Cancer Inst 83 (22): 1620-8, 1991.
  28. Community Intervention Trial for Smoking Cessation (COMMIT): I. cohort results from a four-year community intervention. Am J Public Health 85 (2): 183-92, 1995.
  29. Community intervention trial for smoking cessation (COMMIT): II. Changes in adult cigarette smoking prevalence. Am J Public Health 85 (2): 193-200, 1995.
  30. Hartmann-Boyce J, Chepkin SC, Ye W, et al.: Nicotine replacement therapy versus control for smoking cessation. Cochrane Database Syst Rev 5 (5): CD000146, 2018.
  31. Hartmann-Boyce J, Livingstone-Banks J, Ordóñez-Mena JM, et al.: Behavioural interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 1: CD013229, 2021.
  32. Stead LF, Buitrago D, Preciado N, et al.: Physician advice for smoking cessation. Cochrane Database Syst Rev 2013 (5): CD000165, 2013.
  33. Emmons KM, Puleo E, Park E, et al.: Peer-delivered smoking counseling for childhood cancer survivors increases rate of cessation: the partnership for health study. J Clin Oncol 23 (27): 6516-23, 2005.
  34. Fiore MC, Jaén CR, Baker TB: Treating Tobacco Use and Dependence [Electronic Resource] : 2008 Update. Rockville, Md: Public Health Service, U.S. Department of Health and Human Services, 2008. Available online. Last accessed December 22, 2023.
  35. Glynn TJ, Manley MW, Pechacek TF: Physician-initiated smoking cessation program: the National Cancer Institute trials. Prog Clin Biol Res 339: 11-25, 1990.
  36. Okuyemi KS, Ahluwalia JS, Harris KJ: Pharmacotherapy of smoking cessation. Arch Fam Med 9 (3): 270-81, 2000.
  37. Fiore MC, Bailey WC, Cohen SJ, et al.: Smoking Cessation: Clinical Practice Guideline No 18. US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996. AHCPR Publ No 96-0692.
  38. Tang JL, Law M, Wald N: How effective is nicotine replacement therapy in helping people to stop smoking? BMJ 308 (6920): 21-6, 1994.
  39. Hurt RD, Sachs DP, Glover ED, et al.: A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337 (17): 1195-202, 1997.
  40. Jorenby DE, Leischow SJ, Nides MA, et al.: A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340 (9): 685-91, 1999.
  41. Hughes JR, Goldstein MG, Hurt RD, et al.: Recent advances in the pharmacotherapy of smoking. JAMA 281 (1): 72-6, 1999.
  42. Cahill K, Stevens S, Perera R, et al.: Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 5: CD009329, 2013.
  43. Ray R, Schnoll RA, Lerman C: Pharmacogenetics and smoking cessation with nicotine replacement therapy. CNS Drugs 21 (7): 525-33, 2007.
  44. Fincham JE: Smoking cessation products. In: Covington TR, Berardi RR, Young LL, et al., eds.: Handbook of Nonprescription Drugs. 11th ed. American Pharmaceutical Association, 1996, pp 715-723.
  45. Theodoulou A, Chepkin SC, Ye W, et al.: Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 6 (6): CD013308, 2023.
  46. Baker TB, Piper ME, Stein JH, et al.: Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial. JAMA 315 (4): 371-9, 2016.
  47. Schnoll RA, Patterson F, Wileyto EP, et al.: Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial. Ann Intern Med 152 (3): 144-51, 2010.
  48. Tønnesen P, Paoletti P, Gustavsson G, et al.: Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 13 (2): 238-46, 1999.
  49. Hajizadeh A, Howes S, Theodoulou A, et al.: Antidepressants for smoking cessation. Cochrane Database Syst Rev 5 (5): CD000031, 2023.
  50. Jorenby DE, Hays JT, Rigotti NA, et al.: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296 (1): 56-63, 2006.
  51. Gonzales D, Rennard SI, Nides M, et al.: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296 (1): 47-55, 2006.
  52. Aubin HJ, Bobak A, Britton JR, et al.: Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax 63 (8): 717-24, 2008.
  53. Livingstone-Banks J, Fanshawe TR, Thomas KH, et al.: Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 5 (5): CD006103, 2023.
  54. U.S. Food and Drug Administration: Information for Healthcare Professionals: Varenicline (Marketed as Chantix) and Bupropion (Marketed as Zyban, Wellbutrin, and Generics). Rockville, Md: U.S. Food and Drug Administration, 2009. Archived page available online. Last accessed January 5, 2024.
  55. Anthenelli RM, Benowitz NL, West R, et al.: Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 387 (10037): 2507-20, 2016.
  56. Thomas KH, Martin RM, Knipe DW, et al.: Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ 350: h1109, 2015.
  57. Gibbons RD, Mann JJ: Varenicline, smoking cessation, and neuropsychiatric adverse events. Am J Psychiatry 170 (12): 1460-7, 2013.
  58. Cahill K, Stead LF, Lancaster T: Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev (3): CD006103, 2008.
  59. U.S. Food and Drug Administration: FDA Drug Safety Communication: FDA Revises Description of Mental Health Side Effects of the Stop-Smoking Medicines Chantix (varenicline) and Zyban (bupropion) to Reflect Clinical Trial Findings. U.S. Food and Drug Administration, 2016. Available online. Last accessed May 24, 2024.
  60. Singh S, Loke YK, Spangler JG, et al.: Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ 183 (12): 1359-66, 2011.
  61. Benowitz NL, Pipe A, West R, et al.: Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med 178 (5): 622-631, 2018.
  62. Drug Facts and Comparisons. 54th ed. Facts and Comparisons, 2000.
  63. Hajek P, McRobbie H, Myers K: Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax 68 (11): 1037-42, 2013.
  64. Walker N, Howe C, Glover M, et al.: Cytisine versus nicotine for smoking cessation. N Engl J Med 371 (25): 2353-62, 2014.
  65. Drug Facts and Comparisons. Facts and Comparisons, 1998.
  66. Wagena EJ, Knipschild P, Zeegers MP: Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis. Addiction 100 (3): 317-26, 2005.
  67. Ebbert JO, Hughes JR, West RJ, et al.: Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA 313 (7): 687-94, 2015.
  68. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff: A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med 35 (2): 158-76, 2008.
  69. Lindson-Hawley N, Aveyard P, Hughes JR: Gradual reduction vs abrupt cessation as a smoking cessation strategy in smokers who want to quit. JAMA 310 (1): 91-2, 2013.
  70. Lindson-Hawley N, Banting M, West R, et al.: Gradual Versus Abrupt Smoking Cessation: A Randomized, Controlled Noninferiority Trial. Ann Intern Med 164 (9): 585-92, 2016.
  71. Hughes JR, Carpenter MJ: The feasibility of smoking reduction: an update. Addiction 100 (8): 1074-89, 2005.
  72. Batra A, Klingler K, Landfeldt B, et al.: Smoking reduction treatment with 4-mg nicotine gum: a double-blind, randomized, placebo-controlled study. Clin Pharmacol Ther 78 (6): 689-96, 2005.
  73. Etter JF, Laszlo E: Postintervention effect of nicotine replacement therapy for smoking reduction: a randomized trial with a 5-year follow-up. J Clin Psychopharmacol 27 (2): 151-5, 2007.
  74. Hughes JR, Carpenter MJ: Does smoking reduction increase future cessation and decrease disease risk? A qualitative review. Nicotine Tob Res 8 (6): 739-49, 2006.
  75. Halpern SD, French B, Small DS, et al.: Randomized trial of four financial-incentive programs for smoking cessation. N Engl J Med 372 (22): 2108-17, 2015.
  76. Sunstein CR: Nudging smokers. N Engl J Med 372 (22): 2150-1, 2015.
  77. Popova L, Ling PM: Alternative tobacco product use and smoking cessation: a national study. Am J Public Health 103 (5): 923-30, 2013.
  78. Kamerow D: Big Tobacco lights up e-cigarettes. BMJ 346: f3418, 2013.
  79. Schuster RM, Hertel AW, Mermelstein R: Cigar, cigarillo, and little cigar use among current cigarette-smoking adolescents. Nicotine Tob Res 15 (5): 925-31, 2013.
  80. Jawad M, McEwen A, McNeill A, et al.: To what extent should waterpipe tobacco smoking become a public health priority? Addiction 108 (11): 1873-84, 2013.
  81. Centers for Disease Control and Prevention (CDC): Consumption of cigarettes and combustible tobacco--United States, 2000-2011. MMWR Morb Mortal Wkly Rep 61 (30): 565-9, 2012.
  82. Bullen C, Howe C, Laugesen M, et al.: Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet 382 (9905): 1629-37, 2013.
  83. National Academies of Sciences, Engineering, and Medicine. Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems: Public Health Consequences of E-Cigarettes. The National Academies Press, 2018. Also available online. Last accessed December 22, 2023.
  84. Cullen KA, Gentzke AS, Sawdey MD, et al.: e-Cigarette Use Among Youth in the United States, 2019. JAMA 322 (21): 2095-2103, 2019.
  85. Hajek P, Phillips-Waller A, Przulj D, et al.: A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. N Engl J Med 380 (7): 629-637, 2019.
  86. Halpern SD, Harhay MO, Saulsgiver K, et al.: A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation. N Engl J Med 378 (24): 2302-2310, 2018.
  87. Nabi-Burza E, Drehmer JE, Hipple Walters B, et al.: Treating Parents for Tobacco Use in the Pediatric Setting: The Clinical Effort Against Secondhand Smoke Exposure Cluster Randomized Clinical Trial. JAMA Pediatr 173 (10): 931-939, 2019.

Latest Updates to This Summary (05/24/2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Evidence of Benefit

Added American Cancer Society as reference 4.

Updated statistics on variations in lung cancer mortality rates by U.S. states (cited American Cancer Society [Cancer Prevention & Early Detection Facts & Figures 2023-2024] as reference 17).

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the prevention and cessation of cigarette smoking and the control of tobacco use. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Screening and Prevention Editorial Board. PDQ Cigarette Smoking. Bethesda, MD: National Cancer Institute. Updated . Available at: Accessed . [PMID: 26389444]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.


The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the website can be found on our Contact Us for Help page. Questions can also be submitted to through the website’s Email Us.

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