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Pharmacotherapy, including nicotine replacement therapy (NRT) and prescription drugs, is effective in treating tobacco dependence, increasing quit rates, and increasing long-term smoking abstinence rates in clinical trials.

More than 100 studies have concluded that NRT, bupropion, varenicline, and cytisine are efficacious and safe tobacco dependence treatments. Research shows that smokers in the US, the UK, Canada, and Australia using varenicline, bupropion, or nicotine patches are more likely to succeed in their quit attempts. In the context of behavioral support, bupropion is a useful cessation aid for moderately heavy or heavy smokers, and is at least as effective as single form NRT. Varenicline is more effective than bupropion or single form NRT, and at least as effective as combination NRT. Cytisine is effective for moderately heavy or heavy smokers. The most effective combination of interventions is face-to-face behavioral support together with NRT or varenicline.
While there is insufficient evidence to demonstrate that one form of NRT is more effective than another, data suggest that a higher dose of NRT may be more effective than a lower dose.

However, the evidence of the impact of pharmacotherapy on population smoking cessation trends is mixed. Small population based studies, like a 2012 study in Massachusetts have failed to find a positive effect of NRT use in promoting cessation. Additionally, millions of successful quit attempts were undertaken in the years before NRT was released onto the market and even today, more smokers quit without assistance from pharmacotherapy than with chemical assistance. Based on studies published 2005 and 2012, 54% to 69% of Australian ex-smokers quit unassisted and 41% to 58% of current smokers had attempted to quit unassisted.

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