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Treatment with a nicotine patch and lozenge outperformed four other smoking-cessation therapies in a large clinical trial.

March 01, 2011
Sharon Reynolds, NIDA Notes Staff Writer

In a randomized clinical trial of five smoking-cessation treatments, a combination of the nicotine patch and nicotine lozenge produced the greatest benefit, relative to placebo treatment, in helping people quit smoking and remain abstinent for at least 6 months. Current public health guidelines, based on earlier clinical trials testing individual smoking-cessation aids, recognize that several medications increase smokers' success in kicking the addiction. However, the lack of direct comparisons between smoking-cessation aids has made it difficult for doctors and smokers to choose one treatment over another.

This bar chart displays how many therapies reduce smoking, with type of therapy on the x-axis, the percent of pa Many Therapies Reduce Smoking Abstinence rates for all treatments peaked at the 8-week assessment. Abstinence was confirmed by breath carbon monoxide levels measured during visits to the clinic.

At the start of the study, for example, there had been only one placebo-controlled trial of the lozenge's effectiveness, and the combinations of lozenge plus either nicotine patch or bupropion had never been tested in a clinical trial. The patch, used alone, is currently the most common smoking-cessation aid.

Five Treatments Tested

Researchers at the University of Wisconsin's Transdisciplinary Tobacco Use Research Center designed a comparative effectiveness trial "to permit more-informed decisions about the selection and use of smoking-cessation pharmacotherapies," explains study leader Dr. Megan E. Piper.

In the trial, the researchers tested five treatments side by side to see how each performed relative to a combined placebo group that included a matching placebo for each of the five treatments tested. The participants were 1,504 adults who had smoked more than nine cigarettes a day, on average, for at least the past 6 months. They all wanted to quit and had already tried to do so an average of five to six times. The smokers were, on average, moderately dependent on nicotine, according to the Fagerström Test, which is commonly used to measure nicotine dependence. Each participant was randomly assigned to receive either one of five smoking-cessation regimens—the nicotine lozenge, the nicotine patch, bupropion, the nicotine patch plus the nicotine lozenge, and bupropion plus the nicotine lozenge—or a placebo treatment designed to mimic one of the five regimens. Neither the participants nor the study staff were told who was receiving the active treatments. Varenicline (Chantix), a more recently introduced smoking cessation aid, was not included in the study.

The patients began using bupropion and the bupropion placebo 1 week before their chosen quit date and the other therapies and their respective placebos on the quit date. All the treatment regimens continued for 8 weeks after the quit date except for use of the nicotine lozenge and lozenge placebo, which continued for 12 weeks. All participants received two smoking-cessation counseling sessions before the quit date, one session on the quit date, and three additional sessions during the following 4 weeks.

Most of the patients in every group avoided smoking for at least 1 day during the week following their quit dates, but those receiving the active medications did so at higher rates than those on placebos. The patients assigned to three of the active regimens—the patch plus lozenge, bupropion plus lozenge, and the patch alone—were most likely to be abstinent on day 7 and at the end of the 8-week treatment period (see graph).

At the 6-month followup interviews, however, only the group using the patch plus lozenge had a significantly higher prevalence of abstinence than the placebo recipients, 40 percent versus 22 percent. The patch plus lozenge combination also stood out as being one of two regimens— with bupriopion plus lozenge—that significantly increased, relative to placebo, the number of days from the quit date to relapse, which was defined as smoking on 7 consecutive days. All the active medication regimens except the lozenge alone lengthened the interval between lapsing, defined as taking a first puff on a cigarette after a period of abstinence, and relapsing. This latter finding suggests that continuing medication after a lapse may reduce the chance of a relapse.

Dr. Piper and colleagues note that if they had used the criteria employed by studies that compare a single treatment with placebo, all of the active treatments would have been deemed to outperform the placebos at all time points, with the exception of the lozenge at 1 week after the quit date. However, only the combination of nicotine patch plus lozenge provided a significant advantage under the stringent statistical criteria that are appropriate in studies making multiple comparisons. This suggests that the combination of nicotine patch plus lozenge affords smokers the highest chance of quitting.

Effectiveness Acros the Board

The superiority of the patch plus lozenge combination seen in this trial has several potential explanations, says Dr. Piper. One is that this combination therapy provides two different ways to tackle withdrawal—a steady dose of nicotine from the patch plus the as-needed lozenge to help with transient, strong cravings or challenges induced by an environmental cue. "Alternatively, the effect may be due primarily to the higher nicotine dose from the two mechanisms of administration," she explains.

Dr. Piper says that although the patch plus lozenge showed the best results relative to placebo, the quit rates in all groups—including those receiving a placebo—were unusually high for a smoking-cessation trial. She speculates that this might be attributed to the counseling, which may have been particularly effective, or to the high motivation of the participants, given that they had agreed to be part of a 3-year clinical study of the physical and psychological consequences of smoking cessation.

Dr. Ivan Montoya of NIDA's Division of Pharmacotherapies and Medical Consequences of Drug Abuse says, "This is an important study for clinicians because there is evidence about the best of those five treatments. Based on these results, if I have a patient who wants to quit smoking, of the five treatment choices, I would try my patient first on the patch plus lozenge."

"This study provides a better understanding of what these treatments can do," adds Dr. Piper. "To clinicians who think that they don't have anything to help treat smoking, here's some evidence that there's a lot out there that they can use."


Piper, M.E., et al. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Archives of General Psychiatry 66(11): 1254–1262, 2009. [Full Text (PDF, 385KB)]