With US Food and Drug Administration (FDA) approval of varenicline in May 2006, a new class of drugs became available for tobacco dependence. This α4β2 nicotinic acetylcholine receptor partial agonist was designed as a smoking cessation drug. By releasing dopamine in the brain like nicotine, it prevents craving. However, it also blocks nicotine from binding, thereby preventing the reinforcing effect of continued smoking.
Two RCTs have assessed varenicline against both bupropion and placebo (TABLE 3). Jorenby and colleagues showed that varenicline-treated participants were significantly more likely to be continuously abstinent at 52 weeks than the placebo- or bupropion-treated groups (23% vs 10.3% placebo [OR= 2.66; 95% CI, 1.72–4.11; P<.001 and bupropion ci>P=.004]).24 Gonzales and associates also showed that varenicline-treated smokers were more likely to be continuously abstinent at 52 weeks than the placebo group (21.9% vs 8.4% [OR=3.09; 95% CI, 1.95–4.91; P<.001>25
However, when compared with varenicline, bupropion’s effects were no longer statically significant at 52 weeks (21.9% vs 16.1% [OR=1.46; 95% CI, 0.99– 2.17; P=.057]).
The patient initiating varenicline begins by taking 0.5 mg nightly for 3 nights, then increases to 0.5 mg twice a day for 4 days. The second week, the patient begins the 1-mg twice-daily dosage that is continued through treatment.
Vaccines hold promise
Several promising ideas for the treatment of tobacco dependence are in development, including several vaccines.26 When the immune system produces antibodies to nicotine in response to the vaccine, and when these antibodies bind to the nicotine, the resultant compound is too large to cross the blood–brain barrier. This prevents the reinforcing effect of nicotine. Initial studies of vaccines show that smokers decrease the amount they smoke and find abstinence easier to maintain. However, the vaccine requires frequent boosters to maintain effective antibody titers.
NicVAX from Nabi Biopharmaceuticals was placed on a fast track for approval by the FDA, which is still at least 1 year away. The other two nicotine vaccines are unlikely to be approved for several years.27
Researchers are also studying other compounds that block the euphoria associated with smoking.28 The initial studies of rimonabant (Acomplia), a cannabinoid blocker, have shown that it is no better than other treatments already available. With its indication in some European countries for weight loss, it offered promise as an important option for patients who are concerned about the weight gain associated with smoking cessation. However, the FDA did not approve rimonabant for tobacco cessation when it issued its initial approval letter for weight loss in 2006. Because of safety concerns, the manufacturer subsequently withdrew the new drug application for rimonabant in 2007.
CASE…resolved She kicks the habit
Ann begins taking varenicline the day she leaves the office, and reaches her quit date a week later.
At her 1-month follow-up, she reports that it was easy for her to stay off the cigarettes. With the varenicline, she lost the desire to smoke. The ObGyn reminds her to work on the triggers for her smoking, urging her not to light up when she makes her morning coffee or gets in the car. The physician also suggests that Ann put $4 each morning into a jar on her dresser, so she can see how much she saves now that she isn’t buying cigarettes.
At Ann’s next annual exam, she is marked in the computer as a reformed smoker. She is very proud of that label. When she is asked what she is doing with all that extra cash, she laughs: “My daughter spends it all! But not on cigarettes!”