Combination NRT gets higher quit rates: new study

A new study published this month in the journal “Archives of General Psychiatry” aimed to compare the effectiveness of some of the main medicines for stopping smoking and their combinations. The study, by Dr Megan Piper and colleagues at University of Wisconsin, recruited just over 1500 smokers seeking help to quit, and randomly allocated them to use either, placebo nicotine replacement, the nicotine patch, nicotine lozenge, bupropion tablets, buproion plus nicotine lozenges ,or the patch plus nicotine lozenges.

This was one of the biggest and most ambitious placebo-controlled trials of smoking cessation medicines ever published. Each participant was provided with medication to last a normal course of treatment, as indicated on the product label, plus 6 brief face-to-face counseling sessions. The key questions were:
1. Do each of the individual medicines (patch, lozenge, bupropion) produce higher quit rates than placebo?
2. Do combination medicines produced higher quit rates then individual medicines?

This was a “double-blind” study, meaning that both the participants and the researchers didn’t know who had active medicine and who had placebo, until the study was completed. Most of the medicines were provided for 8 weeks, but the lozenge could be used for 12 weeks after the planned quit date (as is normal according the labeling).

The researchers looked at the proportions of smokers who were quit (no smoking in previous week) at 2 and 6 months after the target quit rate. The quit rates at the 2 month follow-up were as follows:

Placebo : 30%
Patch: 45%
Lozenge: 40%
Bupropion : 40%
Bupropion plus lozenge: 50%
Patch plus lozenge: 54%

At 6 month follow-up the quit rates were:
Placebo : 22%
Patch: 34%
Lozenge: 34%
Bupropion : 32%
Buoropion plus lozenge: 33%
Patch plus lozenge: 40%

Each of the individual medicines achieved higher quit rates than placebo, but the patch plus lozenge combination had higher quit rate again. So these results add to the growing evidence suggesting that combining the nicotine patch plus another NRT is significantly better than either medicine alone.

This study was embedded in a larger 3-year study of factors influencing health, and this may explain the unusually high quit rate in the placebo group. To get into this study all the participants had to be willing to attend numerous appointments over a 3 year period, implying that they were (a) very highly motivated to improve their health and (b) relatively confident in the stability of their life over the coming 3 years.

One other noteworthy aspect of these results was that they appear to confirm the recent trend of results finding bupropion to be equivalent to but no better than NRT for smoking cessation. In the early bupropion trials it looked like bupropion may get slightly higher quit rates than the patch, but more recent studies (including this one) have found bupropion to give very similar outcomes to NRT. Perhaps the most disappointing result in this study was that of bupropion plus lozenge (no better than lozenge alone at 6 months). However, I suspect that this was a fluke poor outcome, caused by a few more participants relapsing after coming off their meds. Although the trial overall is relatively large, each “arm” has only around 250 participants, and so the quit rate is substantially influenced by just a few more people quitting or relapsing.

So this study confirms that the nicotine patch remains a pretty good basic smoking cessation aid, but that adding on another NRT on top of the patch helps more smokers to quit. Other studies suggest that quit rates could be boosted even further by (a) allowing participants to use the patch for a few weeks prior to their target quit date and (b) encouraging those doing well at two months to continue using their NRT for up to 6 months (or as log as needed). This trial did not provide a direct comparison with varenicline (Chantix/Champix) but other studies suggest that varenicline produces quit rates in the same ball park as patch plus another NRT.

We have now been consistently seeing research studies showing that combination NRT is more effective than single NRT for over a decade, and yet the labeling on all of these NRT products continues to warn patients not to combine them. Maybe its time the labeling on these medicines was changed so as not to warn smokers away from using them in the most effective way?

Piper ME, Smith SS, Schlam TR, Fiore MC, Jorenby DE, Fraser D, Baker TB. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies.Arch Gen Psychiatry. 2009 Nov;66(11):1253-62.

This link should take you to the full report on the study:
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About the Author

MA, MAppSci, PhD

Dr. Jonathan Foulds is an expert in the field of tobacco addiction.