Many smokers have successfully quit using a variety of smoking cessation pharmacotherapies. Yet there is little direct evidence on the relative efficacies of these different pharmacotherapies, and without such evidence clinicians and smokers lack a strong empirical basis for recommending or selecting from amongst them. The current paper reports data on the efficacies of five different smoking cessation pharmacotherapies. This research also evaluates the efficacy of the nicotine lozenge, providing additional information on a treatment that has been supported by only one placebo controlled study published to date. Finally, this research evaluates two different medication combinations, one of which (i.e., the nicotine patch + nicotine lozenge) has not been previously evaluated.
There is a great deal of evidence that smoking cessation medications increase the success of a quit smoking attempt.1–4
The 2008 Update to the Public Health Service (PHS) Treating Tobacco Use and Dependence Clinical Practice Guideline
found that five nicotine replacement therapies (NRT’s) and two non-nicotine replacement first-line pharmacotherapies (bupropion SR, varenicline) reliably increase abstinence rates relative to a placebo control.1
However, less is known about the relative
efficacies of these medications. This limitation is due, in part, to a lack of clinical trials that provide “head-to-head” comparisons of different pharmacotherapies within the same study. Cessation studies of individual medications differ in myriad respects which makes it difficult to gauge effectiveness across treatments, even when the individual studies contain a placebo control for the medication. Meta-analyses that attempt to account for interstudy differences may yield conclusions that conflict markedly with large-scale head-to-head trials.5
Without evidence based on head-to-head comparisons, clinicians and smokers lack a strong empirical basis for recommending or selecting from amongst the available smoking cessation medications. Finally, the small number of studies offering head-to-head comparisons yield some conflicting evidence.6, 7
Five pharmacotherapies were selected for comparison in this placebo controlled trial: Nicotine Lozenge, Nicotine Patch, Bupropion, Nicotine Patch + Nicotine Lozenge, and Bupropion + Nicotine Lozenge.1
These therapies were selected for several reasons. The nicotine lozenge was selected because there was limited evidence regarding its efficacy. The 2008 PHS Guideline Update identified only one randomized placebo-controlled trial evaluating the lozenge, and thus gave the lozenge a “B” level strength-of-evidence rating. The single placebo-controlled trial on the lozenge suggests that it is both acceptable to smokers and highly efficacious.8
The nicotine patch was included in this study because it is the most commonly used pharmacotherapy for smoking cessation.6, 9, 10
Given that so many smokers use the nicotine patch, it is important to determine the efficacy of other agents relative to the patch. Finally, it is important to examine the efficacy of the patch because recent data suggest that patch efficacy may have declined over the past 5–10 years.11–13
Bupropion SR was selected because there is modest evidence that it may be more efficacious than the nicotine patch, 11, 14
suggesting that we might observe differential efficacy in the current trial. Also, bupropion has never been directly compared with the nicotine lozenge. Finally, smokers could be encouraged to seek out this prescribed agent, and insurers and health care systems could be encouraged to make this treatment more widely available, if it could be demonstrated that bupropion is more efficacious than over-the-counter (OTC) medication (e.g., the nicotine patch or lozenge).
In addition to the three monotherapies, we tested two combination therapies. Research has generally supported the efficacy of NRT combinations. The 2008 PHS Guideline identified long-term (> 14 weeks) nicotine patch paired with either nicotine gum or nicotine nasal spray as efficacious relative to placebo and relative to the nicotine patch alone.1
A recent Cochrane meta-analysis also found that nicotine patch plus “fast acting” NRT was more effective than monotherapy.2
Combination NRT could be superior to monotherapy for several reasons. For instance, the uses of two NRT’s might produce more adequate nicotine replacement (i.e., higher blood nicotine levels 15
) than a single NRT, although high-dose nicotine patches have not been shown to produce higher abstinence rates than standard-dose patches on a consistent basis.1, 2
Or, it is possible that each type of agent works through a different mechanism, so that having two types produces additive effects. The patch, for instance, produces a steady-state supply of nicotine to prevent severe nicotine withdrawal, and ad libitum
NRT’s (gum, lozenge) provide a means for coping with situational challenges and transient urges to smoke.15, 16
The combination of bupropion plus the nicotine lozenge was also examined because of promising initial results with the nicotine lozenge as a monotherapy.17
Also, the combination of the nicotine patch + bupropion was found to be highly efficacious in the 2008 PHS Guideline meta-analysis (OR = 2.5).1
It is possible that an NRT that permits ad libitum
dosing might produce even better outcomes.
The current research evaluated the five pharmacotherapy interventions on a range of outcome indices, including 6 month 7-day point-prevalence quit rate, a traditional standard for assessing efficacy of smoking cessation interventions.1
This research also determined whether the medications were efficacious in helping a smoker achieve early success (i.e., being able to quit for a week following the quit date) or any success at all (i.e., being able to establish abstinence for at least 1 day during the first week of a quit attempt). In addition, outcomes assessed whether different medications increased the time to first lapse (the first cigarette smoked after quitting) or the time to relapse (smoking on 7 consecutive days following the quit day) or prevented a lapse from becoming a relapse. These different outcomes may help researchers understand the mechanisms of action of different medications and may be helpful in cessation counseling. For instance, if a medication reduces the transition of a lapse to a relapse (e.g., 18
), smokers could be urged to continue medication use despite lapsing.
In sum, this research attempted to gauge the relative efficacies of widely available smoking cessation medications. The results were intended to permit more informed decisions about the selection and use of smoking cessation pharmacotherapies as a means of enhancing treatment effectiveness. .