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FDA-approved pharmacotherapies include various forms of nicotine replacement therapy as well as bupropion and varenicline.

Nicotine Replacement Therapy (NRT)

A variety of formulations of nicotine NRTs are available over the counter—including the transdermal patch, spray, gum, and lozenges—and are equally effective for cessation. NRTs stimulate the brain receptors targeted by nicotine, helping relieve nicotine withdrawal symptoms and cravings that lead to relapse. Many people use NRT to help them get through the early stages of cessation, and those with more severe nicotine addiction can benefit from longer-term treatment.

Use of NRT improves smoking cessation outcomes, and adding behavioral therapies further increases quit rates. A combination of continual nicotine delivery through the transdermal patch and one other form of nicotine taken as needed (e.g., lozenge, gum, nasal spray, inhaler) has been found to be more effective at relieving withdrawal symptoms and cravings than a single type of NRT. Researchers estimate that NRT increases quit rates by 50–70%. Using the patch for up to 24 weeks has been shown to be safe.


Bupropion (immediate-release and extended-release) was originally approved as an antidepressant. It works by inhibiting the reuptake of the brain chemicals norepinephrine and dopamine as well as stimulating their release.

Bupropion has been found to increase quit rates compared with placebo in both short- and long-term follow-up studies and is indicated for smoking cessation. It is equally effective to NRT.


Varenicline helps reduce nicotine cravings by stimulating the alpha-4 beta-2 nicotinic receptor, but to a lesser degree than nicotine.

Varenicline boosts the odds of successfully quitting, compared with unassisted attempts. Varenicline increased the likelihood of quitting (compared with placebo), and some studies find that it is more effective than single forms of NRT and bupropion. In a primary care setting, 44% of patients on varenicline, either alone or combined with counseling, were abstinent at the 2-year follow-up. Patients who participated in group therapy and adhered to the medication were more likely to remain abstinent.

Medication Combinations

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

Other Antidepressants

In addition to bupropion, some other antidepressant medications have also been found effective for smoking cessation, independent of their antidepressant effects, and are considered second-line treatments.

A few small studies suggest that nortriptyline is equally effective as NRT. Although nortriptyline may have side effects in some patients, the small studies for its use in smoking cessation have not reported any.

Researchers have not observed any impact of selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine, and sertraline) on smoking, either alone or in combination with NRT.

Precision Medicine

Researchers have been examining ways to personalize treatment based on important individual biological differences, including genetic differences. The field of pharmacogenetics examines how genes influence therapeutic response to medications, providing critical information to help tailor pharmacotherapies to the individual for maximum benefit. For example, people metabolize nicotine at different rates because of variations in several genes. Individuals who metabolize nicotine quickly smoke more, show greater dependence, and have more difficulty quitting. Such genetic variation influences the therapeutic responses to NRT and other cessation medications.

A recent study compared rates of abstinence 1 week after treatment for slow, normal, and fast metabolizers of nicotine who were randomly assigned to either placebo, NRT, or varenicline. Results indicated that varenicline worked best for normal nicotine metabolizers, whereas NRT patches were most effective for slow metabolizers.