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Does it help to add nicotine gum to bupropion?

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Bupropion (marketed as Zyban for smoking cessation and Wellbutrin for depression) is approved by the US Food and Drug Administration as safe and effective for smoking cessation. It is taken in tablet form. There are also a number of nicotine replacement therapies (nicotine gum, patch, lozenge, inhaler and nasal spray) that are also approved treatments. Some previous studies have suggested that combining medications may improve smoking cessation success rates, and this has become normal practice at the tobacco treatment clinic here at UMDNJ.

Our experience in clinical practice has been that highly addicted smokers have better outcomes if they combine bupropion with NRTs. However, the only way to properly evaluate this is via a randomized placebo-controlled clinical trial. Such as study was just published in the journal, Nicotine & Tobacco Research, by Piper and colleagues at University of Wisconsin. They randomized 608 smokers to receive either (a) bupropion SR tablets plus 4mg nicotine gum, (b) buropion SR tablets plus placebo gum, or (c) placebo tablets and placebo gum, for 8 weeks, along with 6 brief counseling sessions. No more treatment was provided after the 8th week, but the participants were followed up at 6 and 12 months after the initial target quit date.

One week after the quit date, significantly more people had quit smoking while using active bupropion plus 4mg gum (47%), as compared with active bupropion plus placebo gum (38%) or placebo tablets and placebo gum (22%). At the end of treatment (8 weeks), the double medication group still had more successes (38%), as compared with active bupropion (31%) or double placebo (17%). However, at longer term follow-up (i.e. after the participants had stopped taking the medicines) the differences were relatively small. For example, at one year the quit rate was 21% for the double active group, 19% for active bupropion and 14% for double placebo.

So what does all of this mean? Firstly, it suggests that the advantage of adding nicotine gum to bupropion is real and statistically significant, but is quite small, even early in treatment. Secondly, it looks as though much of the advantage of early combination pharmacotherapy disappears at long term follow-up (off all medications). The other thing to note in this study is that the participants only used 4 pieces of gum per day. This is perhaps part of the reason for the smallish effects – the participants were only using smallish amounts of gum. Some may interpret these results as failing to demonstrate that adding nicotine gum to bupropion improves quit rates. Personally, I see a 38% quit rate at end of treatment as being meaningfully better than 31%. The drop-off after the medications are withdrawn is no surprise, and simply challenges us to consider why we continue to treat this chronic condition (tobacco dependence) with acute medications treatments. If a relative of mine was an addicted smoker seeking advice on which medicines to use, I’d probably still encourage something like bupropion plus the 21mg nicotine patch plus 4mg nicotine gum. I’d also encourage them to keep taking the full dose of all these medicines until they had experienced 14 consecutive days with no cravings, withdrawal symptoms or near lapses, and would be surprised if that day came within the first 6 months. Although each individual piece of this treatment may only add a few percent to their chances, this could be a life-saving treatment and every extra chance is worth the effort.
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About the Author


MA, MAppSci, PhD

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

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