When was nicotine replacement therapy invented

Women were slightly overrepresented. Differences between the 2- and the 4-mg lozenge groups were consistent with their selection for low vs high nicotine dependence. Within dependence groups, active-treatment and placebo groups were well matched, with no significant differences between them. Most participants Almost two thirds of participants were taking concomitant medication, most often for gastrointestinal tract or central nervous system conditions.

Table 2 summarizes abstinence rates and results of comparisons at 6, 12, 24, and 52 weeks. For the primary efficacy measure at 6 weeks, the odds of being abstinent were 2. Smokers receiving the active lozenge at either dose continued to demonstrate significantly higher abstinence rates at 12, 24, and 52 weeks. Even after 1 year, the odds of being abstinent were more than doubled by treatment with active lozenge.

We also analyzed the abstinence data by using survival analysis and contrasted active treatment and placebo within each dependence group by using the log-rank test.

Figure 2 shows the resulting Kaplan-Meier survival curves. Figure 2 shows that, whereas high-dependency smokers treated with placebo had poor outcomes relative to those of low-dependency smokers treated with placebo, treatment with active 4-mg lozenges allowed high-dependency smokers to achieve outcomes comparable to those of the low-dependency smokers receiving 2-mg active lozenges, thus eliminating the excess risk due to high dependence. As shown in Table 3 , treatment with the active lozenge significantly reduced baseline-adjusted craving in groups receiving the 2- and the 4-mg lozenges in weeks 1 and 2.

In a parallel analysis of withdrawal symptoms, the active 4-mg lozenge yielded significantly lower withdrawal symptom scores in weeks 1 and 2; for the 2-mg lozenge, using nonparametric analysis, the reduction in symptoms was significant in week 1, but not in week 2.

Similar outcomes were observed when we restricted the analysis to those who were abstinent at week 2. All groups gained weight after smoking cessation. By 6 months, the differences between active and placebo treatment were no longer significant.

In the group assigned to the 2-mg lozenge, treatment assignment had no reliable effect on weight gain. Table 5 shows that The pattern for AEs with some putative relation to study drug was similar to that seen for all events, although the incidence was lower.

Seventeen percent of participants experienced an AE classified as severe. A total of 7. Nonfatal, serious AEs were rare 1. Three deaths occurred during the study; all were among high-dependency smokers assigned to the placebo lozenge. Gastrointestinal and respiratory tract complaints were most frequent.

Only heartburn, hiccup, and nausea occurred significantly more often in the active-treatment than in the placebo groups at both doses. Among respiratory tract events, upper respiratory tract infections 9. Table 6 shows the reported lozenge use at weeks 2, 6, 12, and 24 of the study, as reported by those who were still in the study and providing reports via IVR reporting. At week 2, almost all participants in all groups were using lozenges.

By week 12, use of lozenges had diminished and varied by group and treatment, with the greatest use among high-dependence smokers receiving the active 4-mg lozenge. The number of lozenges used per day also dropped over time for active and placebo groups, as shown in Table 6.

It was hypothesized that the use of more lozenges might improve treatment effects. To test this, groups with high- and low-level lozenge use were formed by splitting participants at the median number of lozenges used per day during the first 2 weeks. As Table 7 shows, the lozenge had significantly greater effect among those who used more lozenges. Using more than the median number of lozenges more than doubled the effect of lozenge treatment on abstinence.

Finally, we assessed whether participants who used more lozenges were more likely to experience AEs. The character and pattern of AEs were similar among high- and low-level lozenge users, but high-level lozenge users were slightly more likely to report AEs Table 5.

Although this trial allocated smokers to nicotine dose on the basis of TTFC, an indicator of nicotine dependence, current indications for nicotine gum allocate dose on the basis of smoking rate divided at 25 cigarettes per day in the United States and 20 in other jurisdictions. Allocating smokers to dose by TTFC results in more smokers receiving the 4-mg dose.

To test the safety of this changed dose allocation, we examined AEs among light smokers who were assigned to the 4-mg lozenge. Their AE reports were similar to those of heavy smokers receiving the 4-mg lozenge. To assess the efficacy implications, we examined treatment efficacy among heavy smokers assigned to the 2-mg lozenge and among light smokers assigned to the 4-mg lozenge. The lozenge showed significant efficacy in both groups.

This study demonstrated the efficacy and safety of 2- and 4-mg nicotine lozenges for smoking cessation. The odds of being abstinent after 6 weeks of treatment were 2. Increased abstinence was maintained even after 1 year since quitting and at least 6 months without lozenges. These data demonstrate the efficacy of the nicotine lozenges and thus add to the database demonstrating NRT efficacy. The absolute success rates and the odds ratios achieved by use of the nicotine lozenge were in the upper range of those observed in previous studies of other forms of NRT, 5 suggesting that this NRT may be particularly effective.

The present success rates were achieved among smokers who had failed to quit smoking while receiving previous pharmacological treatment Table 1. The nicotine lozenge achieved good efficacy even among low-dependency smokers, which was not the case for the sublingual tablet. Many smokers in the trial used the number of lozenges recommended by the product label. The average number of lozenges used peaked at an average of 7 to 9 per day in the first few weeks and dropped over time.

In this study, lozenge use data were only obtained from the subset who provided IVR reports, which may limit generalizability. Within this sample, those who used more lozenges achieved significantly higher success rates and derived more benefit from the active lozenge treatment. This finding is consistent with those on compliance with NRT and with the expected dose-response function. It also suggests that smokers should be encouraged to use at least 7 to 8 lozenges per day.

Use of more lozenges slightly increased AEs, but the increase was not substantial and the events were not serious, and thus this increase does not present a safety concern. Physicians and other health care professionals should encourage patients to avoid underdosing, encourage use of sufficient medication, and dispel patients' unwarranted concerns about the safety of nicotine medications.

One could argue that the high absolute quit rates in this study may also have been enhanced by contacts with the research sites. However, this cannot account for the robust differences between the active-treatment and placebo groups, since all participants received similar treatment at the sites. In any case, smokers in this study were given very little face-to-face behavioral support. The primary vehicle of behavioral advice and support was a written user's guide that provided structure and techniques for quitting smoking.

The face-to-face contacts smokers had with research personnel who were not behavioral specialists were focused on directing their attention to the user's guide and reinforcing it, rather than delivering formal behavioral therapy or introducing additional techniques.

Thus, the results suggest that the nicotine lozenge is suitable for use without adjunctive behavioral treatment. Although the addition of behavioral treatment can boost quit rates, NRT efficacy is independent of the degree of support provided. The use of a simple patient-reported measure of nicotine dependence—TTFC—to allocate smokers to NRT dose may also have helped optimize the treatment. Research has suggested that treating highly dependent smokers with 2 mg of oral nicotine is ineffective, 17 , 18 and one study found that giving low-dependency smokers the 4-mg gum may actually lower their quit rates.

Smokers who smoked heavily but appeared less dependent based on TTFC and were thus assigned to receive the 2-mg lozenge also showed good quit rates and differences between the active-treatment and placebo groups, again implying appropriate dose allocation.

The study did not compare dose allocation based on TTFC with dose allocation based on smoking rate, and thus cannot establish the relative strengths of one regimen over another.

Nevertheless, in the context of other studies of oral NRT dosing, 17 , 20 the data suggest that allocating smokers to the nicotine lozenge dose on the basis of TTFC is an appropriate regimen and may provide better dosing for some smokers.

Assigning smokers to lozenge dose on the basis of TTFC, rather than smoking rate, is likely to result in more smokers being assigned to the 4-mg dose. The nicotine patch was first invented by doctors in at UCLA when they discovered that a transdermal nicotine patch could help people quit smoking. It was the first widely used transdermal medication and has helped millions of smokers give up cigarettes over the last 34 years.

The nicotine patch has been proven to double a quitter's chances of success vs a placebo. Unlike nicotine gum or lozenges that you take throughout the day, the nicotine patch is applied daily. With the patch, you put it on when you wake up and then let it do its job. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. Adverse events associated with nicotine replacement therapy for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving , individuals.

Tob Induc Dis. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf. Safety issues in pharmacotherapy for smoking in patients with cardiovascular disease. Prog Cardiovasc Dis. Safety and effectiveness of transdermal nicotine patch in smokers admitted with acute coronary syndromes.

Am J Cardiol. The impact of pharmaceutical company funding on results of randomized trials of nicotine replacement therapy for smoking cessation: a meta-analysis.

Shape of the relapse curve and long-term abstinence among untreated smokers. Nicotine replacement therapy for long-term smoking cessation: a meta-analysis. Tob Control. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference.

This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv aafp. If you do not wish to leave this website, do not click on the links above. Behavioral support program increases chances of success. Use as directed. The content of this website is intended for US audiences only.

All rights reserved. Get Coupons. Buy Now. Menu Icon.