Tobacco use is the leading preventable cause of death in the United States — approximately 480,000 deaths annually, including cardiovascular disease, lung cancer, COPD, and numerous other smoking-related conditions. Cessation at any age substantially extends life and improves health: quitting before age 40 reduces excess mortality from smoking by about 90%.
Nicotine activates nicotinic acetylcholine receptors throughout the brain, with particularly strong effects on VTA dopamine neurons that drive reward learning. The combination of rapid delivery (smoking achieves brain nicotine levels within seconds of inhalation), strong reward, and frequent reinforcement (many cigarettes per day for many years) produces a particularly compulsive use pattern.
Three FDA-approved pharmacotherapy classes — among the most evidence-based domains in addiction medicine:
Nicotine replacement therapy (NRT): patches (steady-state nicotine), gum (acute craving relief), lozenges (acute craving relief), inhaler, nasal spray. Combination NRT (patch + short-acting form for breakthrough cravings) outperforms single-agent NRT. Available over-the-counter for most forms.
Bupropion (Zyban for cessation): NDRI with reduction in craving and withdrawal effects. Started 1-2 weeks before quit date, continued for 3-6 months. Useful when comorbid depression is present (one medication for both).
Varenicline (Chantix): partial nicotinic receptor agonist with the highest efficacy in head-to-head trials. Started 1-2 weeks before quit date. EAGLES trial confirmed varenicline does not increase neuropsychiatric adverse events compared to NRT or placebo — earlier concerns about depression/suicide were not borne out, but ongoing vigilance reasonable.
Combination therapy: combination NRT (patch + short-acting), or pharmacotherapy plus behavioral support, outperforms single approaches. Adding behavioral support (brief clinician advice, quitlines, structured cessation programs) approximately doubles quit rates compared to pharmacotherapy alone.
E-cigarettes for cessation: emerging evidence suggests e-cigarettes can support smoking cessation, with some studies showing comparable or superior efficacy to NRT in patients motivated to quit. Long-term safety of e-cigarette use itself is not yet established — concerning given recent EVALI experience and persistent youth uptake.
The clinician's role: ask every patient about tobacco use; advise quitting in clear personalized terms; assess readiness; assist with treatment offer (pharmacotherapy + support); arrange follow-up. The "Ask, Advise, Refer" model is brief and effective. Even brief clinician advice doubles quit rates compared to no intervention. Cessation produces the largest single improvement in health for nearly any patient who smokes.
When you encounter a patient who smokes, treatment changes life expectancy. Pharmacotherapy plus behavioral support is the standard of care. The interventions are effective; most patients who attempt cessation with proper support succeed within several attempts.