Table 4. Nicotine Patches continued...
Other Pharmacological Treatments
Other pharmacological treatments include agents targeting nicotine receptors (e.g., varenicline) and agents targeting neurotransmitters (e.g., bupropion HCl) involved in the pathogenesis of nicotine withdrawal and craving. Fluoxetine HCl (Prozac) has also been studied as a treatment for smoking cessation. All three of these treatments carry boxed warnings.
Varenicline is a nicotinic acetylcholine receptor partial agonist and the first U.S. Food and Drug Administration (FDA)-approved prescription pharmacologic agent targeted to these nicotinic receptors.[Level of evidence: I] Although specific mechanisms of action are unknown, it is thought that the agonist properties result in reduced craving and withdrawal by stimulating the release of dopamine and that the antagonist properties prevent inhaled nicotine from binding at the nicotinic receptor sites.
At least 12 published randomized, controlled trials have evaluated varenicline versus placebo (or other approved agents for smoking cessation) for its ability to affect abstinence rates related to smoking or the use of smokeless tobacco.[2,4,5,6,7,8,9,10,11,12,13,14] All studies were relatively large (129-607 patients per arm) and involved multiple sites and countries. In all studies, varenicline was statistically better in achieving abstinence rates as assessed by self-report and carbon monoxide measures than was placebo, and was often better than the other approved smoking cessation comparator arm. Abstinence rates at 12 weeks can be expected to range from 44% to 49% for varenicline versus 11% to 17% for placebo; longer-term rates (52 weeks) range from 14% to 22% for varenicline versus 4% to 8% for placebo.
Most studies evaluated varenicline 1 mg twice a day, using a 1-week titration of 0.5 mg daily for 3 days, 0.5 mg twice a day for 4 days, and then 1 mg twice a day for 11 weeks. However, a few studies evaluated different doses, such as 0.3 mg or 0.5 mg daily or 0.5 mg twice a day, and one study evaluated a flexible dosing schedule during weeks 2 to 12 after all participants were titrated up to 1 mg twice a day in an open-label fashion. From these data, varenicline 0.5 mg twice a day appears to be the minimum dose required to achieve statistically significantly better abstinence rates over placebo.[9,10]