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Varenicline combined with nicotine replacement therapy ups smoking quit rates



An estimated 42 million (18.1%) of the U.S. adult population continues to smoke cigarettes. Effective treatments exist for patients who are willing to avail themselves of such assistance. Varenicline is one of the most effective medications that we have to combat tobacco dependence. However, it doesn’t work for everybody, and questions have remained about how safe and effective it is to combine varenicline with other smoking cessation therapies such as nicotine replacement therapy.

Varenicline binds to a specific nicotine receptor, thereby partially agonizing and blocking it. The result is decreased cravings for tobacco and increased smoking quit rates. Data from early studies conducted by our group suggested that nicotine replacement therapy (NRT) combined with varenicline was safe, but questions remained about its efficacy.

One group of researchers conducted a multicenter clinical trial evaluating the efficacy of combining varenicline and the nicotine patch for increasing smoking cessation rates. Smokers were eligible if they smoked at least 10 cigarettes per day, reported F.N. Coenraad, from the Stellenbosch University, Cape Town, South Africa, and associates. Participants were randomized to active 15-mg nicotine patches or placebo patches started 2 weeks before the target quit date. All participants received varenicline for a total of 14 weeks with a 1-week ramp-up and a 1-week taper. Use of the varenicline in combination with the nicotine patch resulted in increased rates of continuous abstinence from smoking at 12 weeks (no smoking from weeks 9 to 12: 55.4% vs. 40.9%; odds ratio, 1.85; 95% confidence interval, 1.19-2.89; P = .007) and at 24 weeks (no smoking from weeks 9 to 24: 49% vs. 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) (JAMA 2014;312:155-61).

This is a fantastic study answering a lingering question in tobacco control. But what is the theoretical underpinning by which this combination works? Isn’t the NRT blocked by the varenicline? It is possible that the varenicline incompletely saturates the nicotine receptors, which are additionally saturated by the supplemented nicotine. The varenicline effect is mediated through the alpha-4 beta-2 nicotinic receptor, and it is also possible that nicotine binds to nicotine receptor types that varenicline does not bind to, which decreases withdrawal symptoms.

We aren’t exactly sure how this might be working, but a near doubling of the odds of quitting is not to be disregarded. We are also not sure whether the effect holds when one uses other types of NRT such as the nicotine inhaler, nicotine lozenge, nicotine nasal spray, and nicotine gum. In practice, I tend to lean toward a combination of varenicline with the nicotine inhaler since the inhaler can help with some of the behavioral aspects of smoking while the varenicline does its heavy lifting.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. Dr. Ebbert reports receiving research support from Pfizer, manufacturer of varenicline and the nicotine inhaler, and consulting fees from GlaxoSmithKline, manufacturer of the nicotine patch. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

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