Combo therapy for tobacco dependence


The Jan. 8 issue of JAMA marked the 50th anniversary of the first surgeon general’s report on smoking and health. We are all witness to the human catastrophe we call tobacco use. What will future generations think when they look back on us and see that we accepted something that killed so many? Or why we don’t have more medications to treat it – only two new drugs in the last two decades.

I have spent the last 15 years researching how to help people quit tobacco use. One may think that I would have a panel free of patients who continue to smoke – or who may know better than to show up for visits with me.

Far from true. I can think of one patient in particular whom I am watching slowly die from this addiction. Three years ago, his forced expiratory volume in 1 second was 1.04 L, and he continues to smoke a pack of cigarettes per day and is now on supplemental oxygen (although, he tells me, not at the same time).

Tobacco addiction engages a dizzying network of neurotransmitters. Given this complexity, one may wonder if we would gain traction by administering therapies attacking the problem from different angles. Previous research, for example, has shown that combining the nicotine patch with bupropion is better than the nicotine patch alone.

Varenicline is one of the most effective therapies for smoking cessation and acts on the acetylcholine nicotinic receptor. Bupropion, the other first-line nonnicotine drug for smoking cessation, inhibits the reuptake of norepinephrine and dopamine. Some researchers have hypothesized that these medications may act together synergistically.

In that 50th anniversary issue, we published data from our multicenter, randomized clinical trial with our colleagues at the University of Minnesota (JAMA 2014;311:155-63). In this study, we randomized 506 smokers to either combination therapy with bupropion sustained release (SR) and varenicline or varenicline alone given for 3 months.

We were particularly intrigued by the subgroup analysis, which showed that among heavier (20 or more cigarettes per day) and more dependent smokers, combination therapy was superior to monotherapy out to 12 months. Importantly, 12 months is 9 months after stopping the medications.

As a treating clinician who sees smokers in both my primary care and addiction practices, I find these data helpful and motivating.

Helpful because they lead me to conclude that varenicline will work for my lighter smokers, and varenicline combined with bupropion SR may increase the chances of success in heavier ones. As in all good clinical practice, patients should be alerted to the possibility of mood changes and symptoms.

Motivating because I now have data supporting me to step up my game in helping my patients quit before they become another statistic.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. He reported ties to Pfizer, GlaxoSmithKline, Orexigen, and JHP Pharmaceuticals.

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