Testing Rx Combo to Help Smokers Be Smoke Free

Varenicline and bupropion combination therapy for smoking cessation had short term results

(RxWiki News) Smoking causes one in five deaths in the US. Varenicline and bupropion are approved to help smokers quit, but are only partly effective. Using both medications together might work better.

Researchers conducted a clinical study to determine if the combination of bupropion and varenicline worked better than varenicline alone to help smokers quit smoking.

At the 12- and 26-week points in the study, more people who took the combined treatment of bupropion and varenicline had not smoked since their quit date than those who took varenicline alone. There was no difference between the two groups at 52 weeks.

These researchers concluded that more research is needed on combination therapy for smoking cessation.

"Find a smoking cessation program that works for you."

This research was conducted by a team led by Jon O. Ebbert, MD, MSc, from the Nicotine Dependence Center at Mayo Clinic in Rochester, Minnesota.

In this study, 506 adult smokers were randomly assigned to either take varenicline (brand name Chantix) or the combination of varenicline and bupropion (brand name Zyban).  The research was conducted between October 2009 and April 2013 at three clinical research locations.

The people in the study did not know which group they were assigned to. The participants assigned to take varenicline only took 0.5 mg daily for three days, then 0.5 mg twice a day from days four to seven followed by 1 mg daily for 11 weeks. They also took a fake pill (placebo) so that they would not know if they were in the group also taking bupropion.

The participants in the group that took both medications took varenicline on the same dosing schedule as the first group and 150 mg of bupropion daily for days one to three, then 150 mg twice daily until the 12-week time point.

The main goal of the study was to determine smoking abstinence at 12 weeks, measured by those who had not smoked in the last seven days and who had not smoked since two weeks from their quit date. The researchers also determined who was still not smoking at 26 and 52 weeks.

Abstinence from smoking was reported by the study participants and confirmed by the amount of carbon monoxide in their exhaled breath. People in this study completed a daily dairy that recorded smoking urges and withdrawal symptoms using the Minnesota Nicotine Withdrawal Scale (MNWS). The MNWS asked questions about irritability, anxiety, mood, sleeping habits, cravings and restlessness. Weight of participants was also monitored.

Different terms were used to describe when people quit smoking. The target quit date was the seventh day of treatment. The term "7-day point prevalence" was used to describe people who had not smoked in the last seven days. Prolonged abstinence was used when there was no smoking starting from 14 days after the target quit date.

When smoking abstinence was compared between the two experimental groups, the researchers found significant differences at some time points, but not at others.

At the 12-week time point, prolonged smoking abstinence was seen in 53.0 percent of the participants taking the combination of varenicline and bupropion, compared with 43.2 percent of those taking varenicline only.

By 26 weeks, 36.6 percent of the combination treatment group had prolonged abstinence, compared with 27.6 percent in the group taking only varenicline.

At 52 weeks, prolonged abstinence was seen in 30.9 percent of the people taking the combination treatment and 24.5 percent of those taking varenicline only. This difference was not statistically significant.

The percentage of people who had not smoked in the past seven days was not different between the two treatment groups at 12, 26 or 52 weeks.

At 12 weeks, those participants taking the combination of medications had a 1.1-kg weight gain, compared to a 2.5-kg weight gain in the varenicline group alone.

By 26 weeks, the two groups did not have different weight gains, with 3.4 kg gained by the combination therapy group and 3.8 kg gained by the varenicline alone group.

At 52 weeks, the combination group had gained an average of 4.9 kg and the varenicline group alone had gained 6.1 kg. This difference was not significant because of great variation in the weight of the different study participants at 52 weeks.

This study found no significant differences between the two groups in nicotine withdrawal symptoms or cravings after 16 days past the target quit date.

Adverse events were reported by study participants. The most common event was anxiety in people in the combined therapy group. In that group, anxiety was reported in 7.2 percent of the participants, compared with 3.1 percent in the group taking varenicline alone.

Symptoms of depression were also reported in some participants and this was more common in the combined therapy group. Depression symptoms were reported in 3.6 percent of participants taking combined therapy, compared with 0.8 percent of the people taking varenicline alone.

The rates of insomnia were similar between the two treatment groups, with 40.2 percent of the participants taking the combination drug reporting this side effect and  35.4 percent of the varenicline group alone.  Nausea was reported at similar rates, with 21-22 percent of each treatment group reporting nausea.  Headaches were reported by about 8 percent of people in each group and dizziness was reported by 4 percent of the participants in each group.

Outside of this study, serious side effects seen in patients taking varenicline or bupropion prompted the FDA to add a warning to the drugs.  Patients taking either of these medications are advised to contact their physician immediately if they experience  changes in behavior, thinking, or mood, or if they develop suicidal thoughts or actions.

Dr. Ebbert’s team concluded that more research is needed on combination therapy for smoking cessation.

These authors reported some limitations of their study. Since people who were substance abusers and those with serious psychiatric or medical illnesses were not included in the study, the results cannot be interpreted to include the entire population of smokers. Additionally, 38 percent of the participants dropped out of the study and their potential effect on the results cannot be known.

The research was published in the January issue of the JAMA.

Dr. Ebbert disclosed serving as an investigator for research funded by Pfizer, receiving consultant fees from GlaxoSmithKline and receiving research support from Orexigen and JHP Pharmaceuticals outside of the work cited here.

This research was funded by a grant from the National Institutes of Health. Varenicline was provided by Pfizer.

Review Date: 
January 6, 2014