Drugs to Stop Smoking Better Given Together?

By Crystal Phend, Senior Staff Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Doubling up on tobacco cessation drugs helped smokers quit at first, but didn’t significantly improve longer-term abstinence, a trial showed.
Quit rates at 12 weeks were a relative 36% to 49% better with the addition of sustained-release bupropion (Zyban) to varenicline (Chantix), Jon O. Ebbert, MD, MSc, of the Mayo Clinic in Rochester, Minn., and colleagues found.
One year after the 12-week treatment course, though, abstinence had fallen to where the relative 39% to 40% advantage of combination treatment lost significance, the researchers reported in the Jan. 8 issue of the Journal of the American Medical Association.
“Further research is required to determine the role of combination therapy in smoking cessation,” they concluded.
Bupropion and varenicline both tackle cravings and “rewards” from smoking but through somewhat different routes to nicotinic acetylcholine receptors, leading to hopes for additive or synergistic effects, such as with the combination of bupropion and the nicotine patch, the group noted.
Their study randomized 500 adult smokers desiring to quit to take open-label varenicline along with blinded placebo or sustained-release bupropion for 12 weeks.
For the primary outcome, abstinence rates at week 12 were significantly better with the combination in terms of prolonged cessation with no smoking from 2 weeks after the target quit date (53% versus 43.2%, odds ratio 1.49, P=0.03), although not by point-prevalence of no smoking in the prior 7 days (56.2% versus 48.6%, OR 1.36, P=0.09).
By 26 weeks, prolonged abstinence rates had fallen to 36.6% and 27.6% in the two groups, respectively (OR 1.52, P=0.03), and 7-day point-prevalence abstinence to 38.2% and 31.9% (OR 1.32, P=0.14).
At 52 weeks, neither measure showed a significant difference between groups, although the odds ratios remained roughly the same as before (OR 1.39 and 1.40).
Prolonged abstinence rates at that point were 30.9% with combination therapy and 24.5% with varenicline alone (P=0.11); 7-day point-prevalence abstinence rates were 36.6% and 29.2%, respectively (P=0.08).
However, individuals with high levels of baseline nicotine dependence did achieve a significant impact on both measures of abstinence at 52 weeks with the combination versus monotherapy in a sensitivity analysis.
Combination therapy was associated with more adverse events in terms of both anxiety (7.2% versus 3.1%, P=0.04) and depressive symptoms (3.6% versus 0.8%, P=0.03). No serious adverse events in either group were judged treatment related.
Weight gain was similar between groups through the end of follow-up (4.9 kg [11 lbs], and 6.1 kg [13 lbs], P=0.23).
The researchers cautioned that the study was limited by the 38% rate of dropout and limited generalizability “because patients with serious medical and psychiatric illnesses including those with active substance abuse were excluded.”