In a pooled analysis of two randomized studies (total N = 2,052) in which varenicline was directly tested against bupropion SR and a placebo, results showed continuous abstinence rates of 44% with varenicline, 29.7% with bupropion SR, and 17.7% with placebo at weeks 9 through 12. Abstinence rates were followed through week 52 at study end, with varenicline at 22.4%, bupropion SR at 15.4%, and placebo at 9.3%. Factors found in previous studies to predict better quit rates-such as being older, being male, having a lower level of nicotine dependence, smoking fewer baseline cigarettes, and having the first cigarette of the day at a later time-were not found to be predictive of higher quit rates in this pooled analysis.
In June 2011, the FDA updated the prescribing information label for varenicline to warn that the drug may increase the risk of cardiovascular adverse events in patients who have cardiovascular disease. The change is based on findings from a clinical trial of 700 smokers who had cardiovascular disease.
Table 5. Varenicline
bid = twice a day; Rx = prescription.
|Rx||Chantix||0.5 mg/d, days 1-3; 0.5 mg bid, days 4-7; then 1.0 mg bid through week 12||Nausea, insomnia||Risk of toxicity higher in patients with impaired renal function.|
|Not tested in children and pregnant women.|
Bupropion Hydrochloride (HCl)
Also used as an antidepressant, bupropion HCl (Zyban) is a non-nicotine aid to smoking cessation. It is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine and does not inhibit monoamine oxidase. The exact mechanism by which bupropion HCl enhances the ability of patients to abstain from smoking is unknown; however, it is presumed that this action is mediated by noradrenergic or dopaminergic mechanisms. One study [Level of evidence: I] failed to find any additional value of bupropion HCl in reducing relapse in individuals using the nicotine patch compared with a placebo either as part of a relapse prevention program (after the end of successful patch therapy) or as a second-level treatment for individuals who were still smoking after nicotine-patch therapy.
There are concerns that varenicline and bupropion HCl may be associated with an increased risk of depression and other neuropsychiatric events, including suicidal behaviors.[7,8] This concern is based on postmarketing reports and post hoc analyses.[7,8] Attempted and completed suicides have also been reported in patients taking these medications. These neuropsychiatric events have been reported in patients with or without preexisting psychiatric illness.
In July 2009, the FDA required the manufacturers of both varenicline and bupropion HCl to add a boxed warning to the product labeling, based on the continued review of postmarketing adverse event reports. The warning describes the risk of the following neuropsychiatric events from postmarketing reports:[7,9]
- Changes in mood (including depression and mania).
- Homicidal ideation.
- Suicidal ideation, suicide attempts, and completed suicides.