Drug Combo Boosts Early Quit Rates in Smokers

Megan Brooks

January 09, 2014

For smokers motivated to quit, the combination of varenicline (Chantix, Pfizer Inc) and bupropion may boost early, but not long-term, quit rates compared with varenicline alone, a new study shows.

"Additional analyses revealed that combination therapy was better than single-drug therapy long term for heavier and more dependent smokers," Jon Ebbert, MD, of the Mayo Clinic, Rochester, Minnesota, who worked on the study, told Medscape Medical News.

Dr. Ebbert thinks varenicline-bupropion combination therapy "should be considered for heavier and more dependent smokers."

The study was published in the January 8 issue of JAMA, a theme issue on smoking cessation.

In Pursuit of Novel Treatments

The study involved 506 generally healthy, well-educated adults who had smoked at least 10 cigarettes daily for at least 6 months and were motivated to quit. They were randomly allocated to 12 weeks of varenicline plus bupropion SR (n = 249) or varenicline plus placebo (n = 257), with follow-up through week 52. In total, 315 participants (62%) completed the study, 158 on combination therapy and 157 on monotherapy.

The primary outcome was abstinence rates at week 12, defined as prolonged abstinence (no smoking from 2 weeks after the target quit date) and 7-day point-prevalence abstinence (no smoking in the past 7 days). The outcomes were biochemically confirmed.

The researchers found that the combined treatment boosted quit rates at 12 and 26 weeks, but not at 52 weeks.

At week 12, 53.0% of the combination group achieved prolonged smoking abstinence, and 56.2% achieved 7-day point-prevalence smoking abstinence, compared with 43.2% and 48.6% of the patients on varenicline monotherapy, yielding odds ratios (ORs) of 1.49 (P = .03) and 1.36 (P = 0.09), respectively.

At week 26, 36.6% of the combination therapy group had quit, and 38.2% had not smoked in the past 7 days, compared with 27.6% and 31.9% on varenicline monotherapy (OR, 1.52; P = .03; and OR, 1.32; P = .14, respectively).

At the end of follow-up (52 weeks), 30.9% of the combination group had quit, and 36.6% achieved 7-day point-prevalence abstinence, compared with 24.5% and 29.2% on varenicline monotherapy (OR, 1.39; P = .11; and OR, 1.40; P = .08, respectively).

Heavier smokers (at least a pack a day) on combination therapy were more likely to achieve prolonged abstinence at weeks 12, 26, and 52, and 7-day point-prevalence abstinence at 26 and 52 weeks.

Participants on combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03) than the monotherapy group.

"In previous smoking cessation studies with varenicline and bupropion SR, no significant increases in anxiety were observed with either varenicline or bupropion SR compared with placebo," the investigators write. "Bupropion SR is known to be associated with anxiety when used in the treatment of tobacco dependence. Tobacco withdrawal has also been associated with both anxiety and depressive symptoms."

They recommend that all patients treated with pharmacotherapy for tobacco dependence be monitored for changes in anxiety and mood, "an approach consistent with standard clinical practice."

With this study, "we were interested in discovering novel clinical approaches to increase smoking abstinence rates among cigarette smokers wanting to quit," said Dr. Ebbert.

"Prior to this study, no combination therapy with varenicline has been shown to be effective for increasing smoking abstinence rates compared to varenicline as a single-drug therapy," he noted.

Unlikely Treatment Strategy

Commenting on the findings for Medscape Medical News, Daniel Seidman, PhD, who was not involved in the study, said that the varenicline-bupropion combination "might be applicable with heavier smokers but would have to be further studied."

Still, "it seems unlikely many clinicians would use this strategy," said Dr. Seidman, assistant clinical professor of medical psychology (in psychiatry) and director, Smoking Cessation Services, Behavioral Medicine Program, Columbia University Medical Center in New York City.

Dr. Seidman cautioned that the findings may not hold for the general population of smokers because the study population was "more well educated and excluded many of today's smokers who have serious medical and psychiatric illnesses and substance abuse."

The authors acknowledge these limitations in their article.

"The results under ideal conditions are no better than those reported for combination nicotine patch (plus nicotine gum or nicotine spray) in the AHRQ [Agency for Healthcare Research and Quality] clinical practice guidelines at 6 months. Combining 2 forms of nicotine replacement therapies is the combination medication approach which may be the safest and most effective for many of those still smoking, although it is not widely used," he said.

The study was supported by the National Institutes of Health. Varenicline was provided by Pfizer. Dr. Ebbert has served as an investigator on clinical trials funded by Pfizer and has received consultancy fees from GlaxoSmithKline, research support from Pfizer, and research support from Orexigen and JHP Pharmaceuticals. The original article includes a complete list of author disclosures. Dr. Seidman has disclosed no relevant financial relationships.

JAMA. 2014;311:155-163. Abstract

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