A naturalistic cohort study on effectiveness,safety and usage pattern of an over-the-counter nicotine patch. Cohort study on smoking cessation

Introduction Nicotine replacement therapies (NRT) are effective for smoking cessation. After having received over-the-counter (OTC) status in Germany, concerns grew about effectiveness, increased risks, especially of adverse cardiovascular reactions, and inappropriate use of NRT. Thus, a pharmacy-based cohort study was launched.Objectives To assess effectiveness, safety and appropriateness of use of an OTC nicotine patch (Nicotinell, Novartis Ltd.). Every customer who bought an OTC Nicotinell patch was eligible. All data were collected by self-administered questionnaires at weeks 2, 4, 8, 12 and 24 after inclusion. Six hundred and thirty-three customers were admitted, median duration of smoking was 19 years. Of the participants, 6% smoked up to 10 cigarettes per day, 43.6% between 11 and 20, 34.3% between 21 and 30, and 16.1% more than 30 cigarettes. Twenty-four weeks later, 351 participants replied: 28% (177 of 633) had quit smoking completely. Considering replies only the proportion of complete responders raised to 50.4%. There were no serious adverse events reported; 62.9% complied with the directions for use and did not use the patch for more than 3 months. About 45% smoked simultaneously with NRT. Pharmacy-based cohort studies are feasible. This study indicates that the nicotine patch is effective and safe in an OTC setting. There is still room to improve compliance with the directions for use.     

The effect of bupropion on nicotine craving and withdrawal

Rationale and objectives: Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. Methods: During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. Results: Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. Conclusions: Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms. Received: 24 February 1999 / Final version: 15 August 1999     

Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal

Abstract Rationale. Research on the effects of nicotine abstinence and nicotine replacement has not provided consistent information about the impact of replacement therapies on tobacco withdrawal and craving. Objective. This study investigated craving and withdrawal symptoms over a 72-h period of abstinence from cigarettes. Methods. Twenty-four healthy volunteers, not intending to quit smoking, were housed in an experimental unit during three 72-h conditions, consisting of either free smoking, enforced smoking cessation with nicotine replacement therapy (NRT) patches, or enforced smoking cessation with placebo patches. The conditions were adhered to using a randomized crossover design, each separated by at least 10 days of washout. Patches, administered in a double-blind fashion, were given as nicotine (21 mg/24 h) and placebo every 24 h. Self-reported cigarette craving and withdrawal were assessed using multi-item scales at fixed intervals over each condition period. Urinary and plasma cortisol levels were also assayed at fixed intervals over each period. Results. Craving intensity was significantly lower with free smoke than with placebo and with NRT patches than with placebo. No difference in craving levels was found between those who smoked or those who had NRT patches. Withdrawal symptoms were significantly lower with free smoke than with either placebo or NRT patches, but there was no difference in levels of withdrawal between those on NRT patches and those on placebo. During the placebo and NRT patch periods, craving intensity displayed a circadian rhythm, with craving levels lowest in the morning and peaking in the evening. Nicotine delivered via the patch had no impact on these circadian variations in craving. There was no evidence of systematic temporal variations in craving levels during the free smoking period. Conclusions. The data suggested that craving and withdrawal symptoms may be sustained by different physiological pathways, and that only selected components of cigarette craving are influenced by NRT. Electronic Publication     

Rapid absorption of nicotine from new nicotine gum formulations

Rationale

A clinically limiting feature of currently-available nicotine gum is its slow rate of nicotine delivery and consequently slow onset of therapeutic effects. Previous research suggested that a nicotine hydrogen tartrate gum (NHTG1) that delivered nicotine more rapidly provided more effective craving relief. A subsequent gum formulation (NTHG2) was developed to further increase speed of delivery.

Objective

Compare the plasma nicotine absorption and clinical tolerability of NHTG2 to NHTG1 and Nicorette® FreshMint™.

Methods

A single-dose, randomized, crossover study evaluated the early kinetics of nicotine absorption and tolerability of 4 mg NHTG2 compared to NHTG1 and Nicorette.

Results

NHTG2 gum reached higher C_max (p = 0.059 versus Nicorette; p = 0.006 versus NHTG1) and delivered significantly more nicotine than Nicorette or NHTG1 within the first 10-30 min of chewing (AUCs_{0-10, 0-30}) and overall (AUC_0-180). NHT gums and Nicorette were well tolerated, with little difference in their AE profiles.

Conclusions

Study results indicate that NHTG2 gum provided more rapid uptake of nicotine in blood without notable decreases in tolerability. To the extent that rate of delivery and onset of therapeutic effects are related, these gums would be expected to provide more rapid therapeutic effects.     

Effects of instructions on responses to the nicotine patch: a laboratory study

Rationale Smokers have weak positive expectancies for nicotine replacement therapies relative to smoking (Juliano and Brandon, Nicotine Tob Res, 6:569–574, 2004). Objectives This study investigated if a manipulation designed to alter expectancies for the nicotine patch was effective in increasing positive expectancies for the patch and influencing smoking cessation outcomes during a 2-day abstinence period. Materials and methods Smokers (n = 72) were randomly assigned to receive information that emphasized either patch benefits (n = 25) or standard patch information including side effects (n = 25). Participants wore placebo patches but were told that the patches contained nicotine. A control condition (n = 22) was informed that they received placebo patches while given standard patch information to independently test the effect of the nicotine-dose instructional set on abstinence outcomes. Results Benefits information significantly increased positive expectancies for the patch and promoted positive mood during the abstinence period relative to the side effects information. Nicotine-dose instructions resulted in fewer lapsed cigarettes and higher ratings of patch helpfulness than placebo instructions. In particular, women’s smoking behavior appeared to be more influenced by nicotine instructions than that of men. Conclusions The results of this preliminary study suggest that information provided to smokers about patch effects and nicotine content may influence behavioral and subjective outcomes of patch use.     

The influence of offering free transdermal nicotine patches on quit rates in a local health department's smoking cessation program

Nicotine replacement therapy (NRT) has added to the menu of options available to assist cigarette smokers in quit attempts, but cost remains a barrier to access. A quasi-experimental study was carried out to compare quit rates and continuous abstinence from smoking before (n=601) and after (n=311) free nicotine patches were offered to smokers who participated in the Washington County (Maryland) Health Department's "Stop Smoking for Life" group behavioral cessation program. After free NRT was offered, the quit rates upon completion of the program increased from 38% to 65% [difference 27%; 95% confidence limits (CL) 21%, 34%]. The difference in continuos abstinence from smoking between the two groups was no longer statistically significant after 6 months of follow-up, reflecting the more rapid rate of reversion to smoking that occurred during the 18-month follow-up period among the free NRT group who had quit [adjusted rate ratio (RR) 1.35; 95% CL 1.03, 1.78]. Enrollment during the first 18 months after free NRT was 37% greater than the program's first 18 months (P=.08). In conclusion, adding free nicotine patches to a smoking cessation program was associated with increased program enrollment and significantly increased short-term-but not long-term-quit rates. The rapid reversion to smoking in the group who received free nicotine patches could potentially be obviated if participants extend their use of nicotine patches after the free 6-week supply is exhausted.     

Providing accurate safety information may increase a smoker's willingness to use nicotine replacement therapy as part of a quit attempt

Aim

Previous studies have reported that smokers who are misinformed about the safety of Nicotine Replacement Therapy (NRT) are less likely to report using it. In this study, we examined whether providing information that counters these concerns might impact on intentions to use NRT.

Participants

900 smokers recruited from a market research database.

Design and setting

Participants completed an online survey that asked about their views about NRT. Smokers with safety and efficacy concerns were queried to determine whether accurate information might increase their interest in using NRT.

Findings

Misperceptions of NRT safety were common: 93% of smokers did not know that smoking while wearing the nicotine patch does not cause heart attacks; 76% that nicotine gum/lozenge are not as addictive as cigarettes; and 69% that NRT products are not as dangerous as cigarettes. Over half of the smokers with misperceptions reported that they would be more likely to use NRT to help them quit smoking if they were exposed to information correcting their concerns (53%, 58% and 66%, respectively, for each of the misperceptions).

Conclusions

These data suggest that while a sizeable proportion of smokers are still misinformed about the safety of NRT, misinformed smokers would increase consideration of NRT if these misperceptions are addressed by corrective information.     

Short-term efficacy of nicotine replacement therapy for smoking cessation in adolescents: A randomized controlled trial

The aim of this randomized, double-blind placebo-controlled clinical trial is to test the efficacy and safety of nicotine replacement therapy (NRT) in promoting end-of-treatment abstinence among adolescents and whether this relation is moderated by medication compliance. Participants (N = 257, age: 16.7 ± 1.13 years) attended an information meeting followed by a 6- or 9-week treatment. Self-reported smoking cessation, compliance, and side effects were measured by means of online questionnaires. Intent-to-treat analyses showed that independent of compliance, NRT is effective in promoting abstinence rates after 2 weeks (OR = 2.02, 95% CI = 1.11–3.69), but not end-of-treatment abstinence. However, end-of-treatment abstinence rates significantly increased in high-compliant (OR = 1.09, 95% CI = 1.01–1.17) and not in low-compliant participants. No serious adverse events were found. Future research is warranted to disentangle the process involving the decrease in abstinence rates and compliance rates from the third week after the quit date onwards.     

Double-blind placebo controlled trial of dextrose tablets and nicotine patch in smoking cessation

 In a placebo-controlled double-blind trial 308 smokers were individually randomly allocated to one of four groups: 1) 3 g dextrose tablets and 15 mg nicotine transdermal patch; 2) dextrose and placebo patch; 3) placebo tablets and nicotine patch; 4) placebo tablets and placebo patch. Patients were scheduled to attend weekly smokers clinic sessions starting 1 week before the quit date and continue for 4 weeks after that date. The primary outcome variable was biochemically verified abstinence at the final session, four weeks after the scheduled quit date. The proportion of smokers abstinent in the four groups was as follows: 49% – dextrose plus active patch; 44% – dextrose plus placebo patch; 36% – placebo tablet plus active patch; 30% – placebo tablet plus placebo patch. The difference between the dextrose and placebo tablets (13%) was statistically significant (P < 0.01, one-tailed); the difference between the active and placebo patches (6%) was not. There was no significant difference between the effect of the dextrose when accompanied by active versus placebo patches. There was no significant effect of dextrose on weight. The results suggest that dextrose supplementation to the diet may be a cheap and simple aid to giving up smoking. Further research is now needed to establish its long-term efficacy. Received: 7 July 1997/Final version: 26 September 1997     

Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: A randomized trial

Background

Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.

Methods

Smokers (N = 172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.

Results

The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).

Conclusions

For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.     

Manipulation of cigarette craving through rapid smoking: efficacy and effects on smoking behavior

Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior. Received: 2 April 1998/Final version: 7 August 1998     

Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation

Summary The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cotinine (r = 0.93), and the concentration of cotinine in a single sample in the afternoon was well correlated with the AUC_cotinine over 24 h (r = 0.94). The salivary cotinine concentration after 1 week in 60 abstainers was 183 ng · ml^–. After 3, 6 and 12 weeks the cotinine concentrations were 86%, 79% and 59% of the 1-week value. The degree of nicotine compensation attained by the patch after 1 week was 52% (SD 24%) in subjects who succeeded in stopping smoking for at least 3 weeks. A quarter of the subjects achieved a compensation of less than 35% of their usual nicotine intake. Nicotine substitution with this 16-h nicotine patch was stable and the risk of overcompensation was small in this group of smokers.     

Adolescents' self-reported reasons for using nicotine replacement therapy products: a population-based study

Background

Available research provides evidence that adolescents use nicotine replacement therapy (NRT) products. Yet, little is known about reasons and motives behind their use. The present study examined the reasons for NRT use among 14–18-year-old Finnish adolescents.

Method

A national Adolescent Health and Lifestyle Survey was conducted in Finland in 2009 (N = 4834, response rate 55%). Main measures were prevalence of NRT use, self-reported reasons for using NRT and smoking status.

Results

Overall, 10% had used NRT. Boys used NRT more often than girls (11.5% versus 8.7%, p < .001). The three most commonly reported reasons were ‘just try’ (56%), ‘to quit’ (33%) and ‘smoking not possible’ (24%). “Just try” was the most common reason given by non-smokers/experimental smokers whereas daily/occasional smokers used NRT mainly for quitting purposes and when smoking was impossible.

Conclusions

These findings suggest that when planning treatment plans for adolescent smokers, health care personnel should pay particular attention to adolescents' primary reasons and motives for using NRT before suggesting its use.     

Urges to smoke during the first month of abstinence: relationship to relapse and predictors

The urges to smoke reported by 215 former smokers were measured 1 day, 7 days, 14 days and 30 days after they quit to examine: (a) the time course of smoking urges, (b) the relationship of urges to relapse, and (c) predictors of urges to smoke. Urges to smoke were strongest 1 day after quitting, and decreased at each subsequent measurement point. Urges were a powerful predictor of relapse. At each of the four assessment points, abstinent subjects who reported stronger urges to smoke were more likely to relapse by the next measurement point. Urges to smoke at a given day (e.g., day 1) were consistently the best predictors of the persistence of urges at the next assessment (e.g., day 7). Greater negative emotion (e.g., anxiety, sadness, anger, and confusion) and psychosocial stress also predicted stronger urges to smoke. Nicotine gum significantly reduced urges during week 1 post-cessation. Clinical implications of the findings are discussed.     

Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers

Rationale Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette. Objectives The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette. Materials and methods Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus. Results Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels. Conclusion Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation.     

Nicotine dependence, psychological distress and personality traits as possible predictors of smoking cessation. Results of a double-blind study with nicotine patch

Aim

Nicotine replacement therapy (NRT) is an effective treatment for smokers who want to quit, however, the rates of successful quitting can be improved even more. In this context, nicotine dependence (assessed via the Fagerström Tolerance Questionnaire, FTQ), psychological distress (measured via the Symptom Rating Test, SRT), and personality traits (evaluated via the Adult Eysenck Personality Inventory, AEPI) were evaluated as possible predictors of smoking cessation.

Results

A total of 297 cigarette smokers were followed for one year as part of a NRT double-blind, parallel group, randomized trial. Baseline nicotine dependence (weeks 12 and 26: p < 0.05), AEPI neuroticism (weeks 12 and 52: p < 0.05), and AEPI psychoticism (weeks 12 and 52: p < 0.05) scores significantly influenced the outcome of smoking cessation during one-year of follow-up. An increase in psychological distress during follow-up was associated with a lower probability of quitting smoking (p = 0.000).

Conclusions

Nicotine dependence, neuroticism, psychoticism and, over time, psychological distress were the main factors influencing the long-term outcome (i.e., up to 12 months) of smoking cessation under NRT.     

Dependence on the nicotine gum in former smokers

We conducted an Internet survey in 2004–2007 in 526 daily users of the nicotine gum, to assess use of, and dependence on the nicotine gum in former smokers. We used modified versions of the Nicotine Dependence Syndrome Scale (NDSS-G), the Cigarette Dependence Scale (CDS-G) and the Fagerström Test (FTND-G). After 30 days, 155 participants (29%) indicated their gum use. Higher dependence on the gum predicted a lower chance of stopping using it at follow-up (odds ratio = 0.36 for each standard deviation unit on CDS-G, p = 0.001). More long-term (> 3 months) than short-term (< = 3 months) users of the gum agreed with: “I use the nicotine gum because I am addicted to it” (83% vs. 7%, p < .001), and fewer long-term users reported that they used the gum to avoid relapsing to smoking (42% vs. 92%, p < .001). Long-term users had higher ratings of dependence on the gum than short-term users, as assessed with NDSS-Gum, CDS-Gum and FTND-Gum (all p < .001). Most long-term users reported symptoms of dependence on the nicotine gum. Lower levels of dependence on the gum predicted cessation of gum use. However, long term use of the nicotine gum has no known serious adverse consequence, and may be beneficial if it prevents late relapse.     

The effect of varying the nicotine content of cigarettes on human smoking behaviour

9 subjects were given cigarettes to smoke containing 3 different amounts of nicotine. It was found that the larger the content of nicotine in the cigarettes offered the smaller was the number smoked during the 8-h period. A linear relationship between nicotine content and time to smoke a single cigaretts was found such that the more nicotine there was in a cigarette the longer a subject took to smoke it.     

Effects of D-cycloserine on cue-induced craving and cigarette smoking among concurrent cocaine- and nicotine-dependent volunteers

Rates of cigarette smoking are 3- to 4-fold greater among those with cocaine-dependence, and compared to non-users, cocaine users are at greater risk of incurring smoking-related negative health effects and death. The current study examined D-cycloserine's (0 or 50 mg once weekly) effects on 1) extinction of cue-induced craving for cigarettes, 2) cigarette smoking in conjunction with cognitive–behavioral therapy, and 3) safety and tolerability in cocaine-dependent smokers. This was a double-blind, placebo-controlled, between groups, outpatient study. Participants (N = 29) were concurrent cocaine- and nicotine-dependent volunteers seeking treatment for their cigarette smoking. Study visits were 3 times per week for 4 consecutive weeks. At each visit, participants received cognitive–behavioral therapy for smoking, were exposed to smoking cues. A subset of participants (N = 22) returned for 6-month follow-up visits. While craving decreased, no significant effects of D-cycloserine treatment were observed. Likewise, significant decreases in smoking were observed at study days 6 (p < 0.002) and 12 (p < 0.0001) relative to baseline, although no participants achieved complete abstinence. However, there was no effect of D-cycloserine on cigarette smoking during treatment or at 6-mos follow-up. The treatment was safe and tolerable, with nearly 90% of treatment sessions attended based on an intent-to-treat analysis. While no effects of D-cycloserine on craving or smoking were observed in the current study, the results do suggest that smoking treatment is well accepted and may be effective for cocaine-dependent individuals.