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Nicotine Addiction
Benjamin N. Schneider, MD
Kamala Nyamathi, MD
image BASICS
Nicotine addiction is the constellation of signs of dependence and compulsive use despite knowledge of its adverse effects.
20-25% of the U.S. population use nicotine.
70 million people in the United States ≥12 years of age reported current use of tobacco (58.7 million smoked cigarettes, 13.3 million cigars, 2.1 million pipes, and 8.6 million used smokeless tobacco) (1).
Pediatric Considerations
Nicotine use is common and underrecognized in this population. Use of cigarettes; smokeless tobacco; and now, e-cigarettes in the past month: 8th graders: 4%, 3%, and 8.7%; 10th graders: 7.2%, 5.3%, and 16.2%; 12th graders: 13.6%, 8.4%, and 17% (2).
  • Similar to other addictive drugs, nicotine affects neural pathways that control reward and pleasure.
  • Nicotinic acetylcholine receptors (nAChRs) are thought to play a major role in nicotine's effect on brain chemistry via their influence of glutamate, GABA, dopamine, serotonin, acetylcholine, and norepinephrine.
  • Through these neurotransmitters, nicotine induces euphoria, assists in information processing, and reduces anxiety and fatigue.
  • Polymorphisms in neuronal nAChR genes are associated with increased susceptibility to dependence.
  • Specific genes associated with nicotine dependence have been linked with decreased activity of CYP2B86 (an enzyme that breaks down brain nicotine) and are thought to cause increased cravings. These patients are 1.5 times more likely to fail treatment.
  • Mental illness (depression, posttraumatic stress disorder, bipolar disorder, and schizophrenia)
  • Low socioeconomic status
  • Low educational status
  • Early first-hand nicotine experience
  • Concurrent substance abuse
  • Home and peer influence
  • The U.S. Preventive Services Task Force (USPSTF) strongly recommends clinicians screen all:
    • Adults for tobacco use and provide cessation interventions for those who screened positive (Grade A).
    • Pregnant women for tobacco use and provide pregnancy-tailored counseling to those who screened positive (Grade A).
  • The USPSTF recommends that clinicians provide interventions, including education or brief counseling to prevent initiation of tobacco use among schoolaged children and adolescents (Grade B).
Pregnancy Considerations
  • Carbon monoxide and nicotine interfere with fetal oxygen supply, resulting in decreased birth weights and possible intrauterine growth restriction
  • Maternal smoking adversely affects fetal lung development, with lifelong decreases in pulmonary function and increased asthma risk.
  • Smoking is associated with increased risk of spontaneous abortion, sudden infant death syndrome, learning and behavioral problems, and increased risk of childhood obesity.
  • Chronic obstructive pulmonary disease (COPD) (emphysema and chronic bronchitis)
  • Cancers (lung, oral/pharyngeal, kidney, bladder, cervical, anal)
  • Atherosclerotic disease
  • Periodontal disease
  • Cardiovascular exam
  • Pulmonary exam
Not applicable
  • Low-dose CT scan: recommended by The American College of Chest Physicians for individuals age 55 to 75 years old with a history of 30+ pack years who are currently smoking or have quit within the past 15 years (unless they have comorbidities that are anticipated to limit life expectancy)
  • Spirometry: not recommended for routine screening, only if COPD is suspected
  • Advice from providers improves quit rate number needed to treat [NNT] 75.
  • Providing brief, simple advice about cessation increases the likelihood of sustained cessation at 12 months.
  • More intensive advice (i.e., motivational interviewing) may result in higher rates of quitting.
  • Providing follow-up support may increase quit rates slightly.
  • Brief strategies to help the patient willing to quit tobacco use—the “5 As” (4)[A]
    • Ask patient if he or she uses nicotine.
    • Advise him or her to quit.
    • Assess willingness to make a quit attempt.
    • Assist those willing to make a quit attempt.
    • Arrange for follow-up contact to prevent relapse.
  • Enhancing motivation to quit—the “5 Rs” (4)[A]
    • Relevance: Encourage patient to indicate why quitting is personally relevant.
    • Risks: Ask patient to identify potential negative consequences of use.
    • Rewards: Ask patient to identify potential benefits of cessation.
    • Roadblocks: Ask patient to identify barriers or impediments to quitting and provide treatment (e.g., problem-solving counseling or medication) that could address barriers.
    • Repetition: This motivational intervention should be repeated each visit.
  • Users should be given a choice of quitting methods.
  • Quit rates are equivalent for tapering nicotine use versus abrupt cessation. Patient preference should be part of the plan.
  • Seven FDA-approved medications exist: nicotine replacement therapy (NRT), both long acting (i.e., patch) and short acting (i.e., gum, inhaler, lozenge, nasal spray), and non-NRT meds like bupropion SR and varenicline.
  • With few exceptions, the choice of a first-line medication depends on patient preference.
  • Combination NRT: All forms of NRT increase quit rate (5)[A] 50-70%. Combining long-acting and short-acting NRTs is more effective than using any single method alone. Heavier users may need higher doses. Starting NRT before planned quit date may increase the chances of success.
  • Nicotine replacement (Gum: pregnancy Category C all other formulations are pregnancy Category D).
    • Nicotine transdermal (NicoDerm CQ): For > 10 cigarettes/day, start with 21 mg patch/day for 6 weeks, then 14 mg patch/day for 2 weeks, then 7 mg patch/day for 2 weeks; for use of <10 cigarettes/day, start with 14 mg patch/day for 6 weeks, then 7 mg patch/day for 2 weeks. Extending use of the patch beyond 8 to 10 weeks may improve abstinence rates.
  • Nicotine gum (Nicorette): For >25 cigarettes/day habit, use 4 mg gum q1-2h for 6 weeks; for <25 cigarettes/day habit, use 2 mg gum q1-2h for 6 weeks; decrease dosing by q1-2h for 3 weeks; chew then tuck between cheek and gingiva once nicotine flavor is released, repeat up to 30 minutes then discard.
  • Nicotine lozenge (Commit): for patients who smoke their first cigarette within 30 minutes of waking, 4 mg lozenge PO q1-2h for 6 weeks; first cigarette >30 minutes after waking, 2 mg lozenge PO q1-2h for 6 weeks; decrease dosing by q1-2h for 3 weeks
  • Nicotine nasal (Nicotrol NS): 1 to 2 sprays (0.5 mg/spray) each nostril q1h for 8 weeks, then taper; max 10 sprays/hr and 80 sprays/day
  • Nicotine inhaler (Nicotrol inhaler): 6 to 16 cartridges inhaled (4 mg/cartridge) per day for 6 to 12 weeks, then taper; incorporates the behavioral and sensory aspects of smoking
  • Varenicline is a nicotinic acetylcholine partial agonist. Trials have suggested this agent may be more efficacious than bupropion (6)[A]. Longer term therapy (up to 24 weeks) may delay or prevent relapse:
    • Starter pack: 0.5 mg/day for 3 days, 0.5 mg BID for 4 days, 1 mg/day starting on day 7
      • Maintenance pack 1 mg BID continue for 12 weeks total; if successful in quitting, may continue for another 12 weeks.

  • Varenicline + bupropion has not been shown to be more effective than either agent alone but with increased side effects.
  • Varenicline + nicotine replacement has been shown to be more effective at 6 months than varenicline alone (NNT 6 [B]).
  • Bupropion SR is an atypical antidepressant and norepinephrine-dopamine reuptake inhibitor.
    • Start 1 week before a target quit date due to time needed to reach steady state.
    • Use 150 mg/day for 3 days, then 150 mg twice a day for 7 to 12 weeks.
  • Nortriptyline is a tricyclic antidepressant.
    • Start 25 mg/day, gradually increase to target dose of 75 to 100 mg/day and continue for 12 weeks.
    • Stop smoking 2 to 4 weeks after starting treatment.
  • Users who get support from partners and others are more likely to quit.
  • Group programs double cessation rates compared to self-help materials. It is unclear whether groups are better than individual counseling or other advice, but they are more effective than no treatment. Not all users making a quit attempt want to attend meetings, but for those who do, they are likely to be helpful.
  • E-cigarettes improve abstinence at 1 month versus placebo, but this effect is lost at 3- and 6-month follow up. Adverse effects include dry cough (26-32%), throat irritation (7-32%), and shortness of breath (2-20%) (7).
  • New data suggest that certain e-cigarette flavorings may alter lung functioning on a cellular level (8).
Pregnancy Considerations
  • Smoking is associated with decreased intrauterine growth restriction, placenta previa, abruptio placentae, decreased maternal thyroid function, preterm premature rupture of membranes, low birth weight, perinatal mortality, and ectopic pregnancy.
  • Quitting smoking before 15 weeks' gestation provides the greatest benefit for both the woman and fetus, but quitting any time is beneficial.
  • There is still insufficient data regarding the safety and efficacy of NRT in pregnancy (gum is considered as Category C, while remaining NRTs are Category D).
  • Similarly, little is known about the effects of varenicline and bupropion on fetal development (Category C).
  • It is recommended that pregnant women be offered behavioral therapy and education with NRT and medications reserved for patients in need of additional assistance (9).
  • NRT is metabolized faster in pregnant women, so higher doses may be required.
  • Acupuncture: no consistent evidence of efficacy
  • Hypnotherapy: no consistent evidence of efficacy
  • Programs to stop use that begin during hospitalization and include follow-up support after discharge are effective.
  • Programs are effective for all hospitalized users, regardless of admitting diagnosis (10)[A].
  • Consider NRT for all inpatients who use nicotine to decrease withdrawal symptoms (10)[A].
  • Patients motivated to quit smoking and who have initiated therapy should follow up 1 to 2 weeks after initiation of therapy to monitor response and observe for any medication side effects.
  • Encourage routine exercise as a component of smoking-cessation treatment.
Weight gain (4 to 5 kg over 10 years) possible after smoking cessation
  • http://smokefree.gov/
  • http://women.smokefree.gov/
  • http://teen.smokefree.gov
  • http://www.nicotine-anonymous.org
  • https://quitnet.meyouhealth.com/#/
  • 1-877-44U-QUIT (1-877-448-7848)
  • >85% of those who try to quit on their own relapse, most within a week.
  • Approximately 50-60% of women who quit smoking in pregnancy return to smoking within 1-year postpartum.
  • Cessation medications and techniques listed above significantly improve cessation.
1. National Institute on Drug Abuse. Tobacco Addiction. NIH Publication Number 09-4342. Bethesda, MD: National Institute of Health; 2009.
2. Johnston LD, O'Malley PM, Bachman JG, et al. Monitoring the Future, National Results on Adolescent Drug Use: Overview of Key Findings, 2011. Ann Arbor, MI: Institute for Social Research, University of Michigan; 2012.
3. Stead LF, Bergson G, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev. 2008;(2):CD000165.
4. National Guideline Clearinghouse (NGC). Guideline synthesis: Tobacco use cessation. In: National Guideline Clearinghouse (NGC). Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2001. http://www.guideline.gov.
5. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2011;(11):CD000146.
6. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2012;(4):CD006103.
7. Allehebi RO, Khan MH, Stanbrook MB. Efficacy and safety of electronic cigarettes for smoking cessation: a systematic review. Am J Respir Crit Care Med. 191;2015:A3715.
8. Rowell TR, Lee s, Tarran R. Select e-cigarette flavors alter calcium signaling, cell viability and proliferation in lung epithelia. Am J Respir Crit Care Med. 191;2015:A2896.
9. American College of Obstetricians and Gynecologists. Committee Opinion No. 471: smoking cessation during pregnancy. 2010;116(5):1241-1244.
10. Rigotti NA, Clair C, Munafò MR, et al. Interventions for smoking cessation in hospitalised patients. Cochrane Database Syst Rev. 2012;(5):CD001837.
Additional Reading
  • Benowitz NL. Nicotine addiction. N Engl J Med. 2010;362(24):2295-2303.
  • Centers for Disease Control and Prevention. Smoking and tobacco use: http://www.cdc.gov/tobacco/index.htm.
  • 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. 2008;35(2):158-176.
  • Civljak M, Stead LF, Hartmann-Boyce J, et al. Internet-based interventions for smoking cessation. Cochrane Database Syst Rev. 2013;(7):CD007078.
  • The Health Consequences of Smoking- 50 years of Progress: A Report of the Surgeon General, 2014 http://www.surgeongeneral.gov/library/reports/50-years-of-progress/. Especially Appendix 14.4, Treatment for Tobacco Use and Dependence.
  • Wilson JF. In the clinic. Smoking cessation. Ann Intern Med. 2007;146(3):ITC2-1-ICT2-16.
  • F17.200 Nicotine dependence, unspecified, uncomplicated
  • F17.201 Nicotine dependence, unspecified, in remission
  • F17.203 Nicotine dependence unspecified, with withdrawal
Clinical Pearls
  • Nicotine and particularly smoking cessation should be encouraged for all patients who use.
  • Consider NRT for all hospitalized patients who smoke to decrease withdrawal symptoms.
  • Treatments, including but not limited to medications significantly increase the rate of long-term abstinence.
  • No single type of NRT/medication is best; thus, the choice should be based on patient preference and risk factors for side effects.
  • Nicotine dependence is a chronic disease and will often require repeated interventions and multiple cessation attempts.