The oral medication varenicline (Chantix), the first smoking-cessation aid to be approved in nearly a decade, provides double-barreled action that may help many of the 44.5 million smokers in the United States to stop their addiction for good. Every year, almost 41% of smokers try to quit, and only about 1 in 10 is successful.

In addition to quelling nicotine withdrawal symptoms, varenicline blocks some of the pleasurable effects of nicotine that often compel quitters to resume smoking.

Varenicline received FDA approval in 2006 via the fast-track review process because of the potentially significant health benefits it offered as well as the high level of the clinical evidence.

Dopamine is at the heart of all addictions. The problem is magnified in smoking because the strong addictive component in nicotine is accompanied by a strong behavioral component. Nicotine smoking is a strong habit-forming behavior that is compounded by the physiologic components of addiction.

Five of the 6 available agents for smoking cessation are nicotine replacements in the form of gum, patch, nasal spray, oral inhaler, and lozenge. Nicotine replacement therapy delivers nicotine slower and more leveled out, without the arterial spikes that occur with inhalation and thus without the huge release of dopamine associated with smoking proper.

The other oral therapy available—sustained-release bupropion (Zyban)—works along dopaminergic and noradrenergic pathways to remove some of the reward from nicotine. Varenicline also attacks the reward system, but it does so even more aggressively than bupropion.

Varenicline is indicated for adults older than 18 years who are motivated to quit smoking. The starting dosage is 0.5 mg/day and is titrated in the first week to 1 mg twice daily, for 12 weeks. Those who cannot quit smoking after 12 weeks may continue taking it for an additional 12 weeks.

The most common side effect reported with varenicline in clinical trials was nausea. It is therefore recommended to take the medication after a meal, with water, which may help reduce this event. Most cases were low to moderate. The few cases of severe nausea reported were equally divided between the 3 groups (varenicline, bupropion, placebo).

Significant Evidence
The safety and efficacy of varenicline were confirmed in 3 large, randomized, controlled trials that included more than 3200 participants. The first 2 trials included 2052 healthy adults (aged 18-75 years) who smoked at least 10 cigarettes daily and had not been able to quit smoking for more than 3 months during the previous year. Participants were randomized to 12 weeks of treatment with varenicline, bupropion, or placebo (JAMA. 2006; 296:47-55; 56-63).

During the last 4 weeks of treatment, varenicline-treated patients were about 4 times more likely to be abstinent than placebo-treated patients and about twice more likely to be abstinent than bupropion-treated patients. Varenicline continued to outperform bupropion therapy and placebo even after treatment had ended (Table).

And even though almost 30% of patients treated with varenicline complained of nausea, those treated with bupropion were more likely to withdraw because of side effects than those receiving varenicline.

The third study compared 12 weeks of varenicline maintenance therapy with placebo in patients who were able to abstain from smoking for at least 7 days after 12 weeks of varenicline treatment (JAMA. 2006;296:64-71).

In that study, patients in the varenicline group were significantly more likely to continue abstaining from smoking at weeks 13 to 24 compared with those taking placebo as well as at weeks 13 to 52.

Counsel Patients
Because habit and addiction are intertwined in smoking, supplementing with patient counseling is necessary. Furthermore, smoking is associated with a high degree of relapse and a periodic check is therefore recommended. Traumatic events and other stressors can trigger a relapse. It is not sufficient to prescribe therapy without some type of monitoring for the first few months.

A website devoted to varenicline (www.get-quit.com) offers daily feedback for those trying to quit smoking.