Effectiveness of a transdermal nicotine system in smoking cessation studies

To investigate the effectiveness and tolerability of a transdermal nicotine system (TNS) as an aid towards easing smoking cessation, two double-blind placebo-controlled randomized field studies were performed. The TNS was available in sizes of 10, 20 and 30 cm2, delivering 7, 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors (Practitioner Study). This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group. The second trial was performed in 112 young people, 56 in each treatment group, at the Universities of Basle and Zurich (University Study). The placebo and the nicotine groups were comparable in both studies. Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system. When abstinence, as verified by CO measurements, was achieved, the next smaller system was applied. In the Practitioner Study, the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks' treatment period took place every 3 weeks. Abstainers in both studies will be followed up until 12 months after treatment was begun. After 1, 2 and 3 months of treatment 41%, 36% and 36% of the participants in the nicotine group of the Practitioner Study were abstinent. The corresponding figures in the placebo group were 19.4%, 20.4% and 22.5%. The differences were statistically significant for all three months (p = 0.001; p = 0.018 and p = 0.043). Body weight did not increase in the TNS group, but did in the placebo group (+ 4.4 kg). The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution. Abstinence rates in the University Study were initially higher with 51.8% in the nicotine group and 28.6% in the placebo group after 3 weeks of treatment, but then declined to 42.9% after 6 weeks and 39.3% after 9 weeks in the nicotine group and to 25% and 19.6%, respectively, in the placebo group. The differences between the groups were statistically significant on all 3 occasions, with p = 0.012, p = 0.046 and p = 0.023.(ABSTRACT TRUNCATED AT 250 WORDS)     

Varenicline: progress in smoking cessation treatment

Varenicline is the first pharmacological aid for smoking cessation treatment to be approved in almost a decade. Varenicline is an alpha4beta2 nicotinic acetylcholine receptor partial agonist. It may assist those who wish to quit smoking by producing partial activation at nicotinic receptors to ease craving and withdrawal symptoms; and by simultaneously blocking the effects of nicotine from cigarettes smoked, thereby reducing the satisfaction of continued smoking. The effectiveness of varenicline as an aid for smoking cessation has been demonstrated in several clinical trials versus placebo and sustained release bupropion. In addition, varenicline is well tolerated and has an acceptable safety profile. As an aid for smoking cessation, varenicline offers progress in the treatment of tobacco dependence.     

Combination of behavioral smoking cessation with transdermal nicotine substitution

Effects of a transdermal nicotine substitution on psychological smoking cessation were investigated in a double-blind prospective study. 131 smokers were randomly assigned to three treatment conditions: All smokers underwent nine weeks of self-controlled smoking cessation. During six weeks one group was additionally treated with nicotine patches continuously releasing nicotine through the skin into the blood circuit. The second group received placebo patches; while the third group was treated with behavioral training alone. Treatment effects were measured by daily cigarette consumption. Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment than both placebo- and control-subjects: 69% in the nicotine condition, 51.2% and 44.4% under placebo and control conditions respectively. Effects are influenced by initial cigarette consumption, with the light smokers benefitting most from the nicotine patch. Self-assessments suggest an aversive effect of transdermal nicotine on cigarette taste. Our results, although not yet verified by long-term observations, demonstrate that transdermal nicotine substitution significantly enhances the effectiveness of behavioral smoking cessation methods.     

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.     

Varenicline: new treatment with efficacy in smoking cessation

Smoking is a significant public health problem, and existing treatments have demonstrated only moderate efficacy in assisting smokers to quit. Varenicline, recently approved by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products as an aid to smoking cessation treatment, has a novel mechanism of action, targeting the specific nicotinic acetylcholine receptor (nAChR) associated with nicotine-induced behaviors (alpha4beta2 nAChR). It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. The clinical efficacy and tolerability of varenicline has been demonstrated in phase III clinical trials involving more than 2,000 cigarette smokers. At the end of the treatment period in two 12-week, multicenter, randomized, double-blind, placebo-controlled studies, patients receiving varenicline (1 mg twice daily) experienced an increase in the odds of quitting smoking by nearly fourfold compared with those receiving placebo, and almost twofold compared with the odds for patients receiving 150 mg bupropion SR (sustained release) twice daily. In these two trials where patients were randomized to either varenicline or bupropion, the efficacy of varenicline was consistently superior at 12 weeks; this result sustained significance at 24 weeks in both studies and up to 52 weeks in one study. Nausea, a common adverse event reported in clinical trials, led to few treatment discontinuations. Its targeted mechanism of action, superior efficacy and excellent tolerability make varenicline a welcome and useful addition to the therapeutic options for smoking cessation.     

Effectiveness of varenicline for smoking cessation: a 1-year follow-up study

We examined the rate of smoking cessation associated with 6 weeks of group counseling therapy (GCT) given alone or in combination with 12 weeks of varenicline (VAR) in 112 smokers. Follow-ups were conducted at 12, 26, and 52 weeks post enrollment. Since participants chose the treatment, differences between the two groups were adjusted using propensity matching. Only 33.3% completed VAR treatment, yet at 1 year, the abstinence rate among participants who were not compliant was not different from subjects who were compliant. VAR resulted in a 23% improvement in the abstinence rates at 26 and 52 weeks (GCT + VAR rates were 62.5% and 56.3%, respectively; GCT-only rates were 39.6% and 33.3%, respectively). Increased carbon monoxide concentration, cigarette consumption, and Beck Depression Inventory score were associated with continued smoking. In conclusion, we found that the combination of counseling and VAR is effective at promoting abstinence at 1 year even when compliance with the medication is not 100%.     

A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch

Rationale

Monoamine oxidase B (MAO-B) activity is reduced in smokers. A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a candidate drug for smoking cessation.

Objective

This study aims to determine the efficacy and safety of EVT302, a selective reversible MAO-B inhibitor, alone and on top of nicotine patch (NP) in smoking cessation.

Methods

This was a randomised, double blind, placebo-controlled phase II, multicentre trial. Smokers (≥10 cigarettes/day) received either EVT302 (N?=?145) or placebo (N?=?145), or EVT302 (N?=?61) or placebo (N?=?61) on top of open label NP 21 mg/day for 8 weeks. The main comparison was between EVT302 and placebo without NP. The primary outcome measure was end-of-treatment 4-week continuous abstinence rate (CAR). Secondary outcome measures: point prevalence abstinence rate, saliva cotinine concentrations in the groups without NP, urge to smoke, nicotine withdrawal symptoms and assessment of subjective effects of cigarettes.

Results

The 4-week CAR was 15.2 % in the placebo, 17.2 % in the EVT302, 26.8 % in the NP?+?placebo and 32.8 % in the NP?+?EVT302 groups, respectively. There was no difference between EVT302 and placebo either alone (adjusted OR: 1.45, 95 % CI: 0.65–3.26) or when co-administered with NP. No statistically significant difference occurred for the secondary outcome measures.

Conclusions

The selective, reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit, in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation. Co-administration of NP does not provide a supplementary benefit.     

Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: A validation study

Transdermal nicotine is widely used for smoking cessation, but only ~ 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3′-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were ~ 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR = .54 [95% CI:.36-.82], p = .003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (β = − 3.38, t[355] = − 3.09, p < .05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.     

Transdermal nicotine in smoking cessation

Summary A systematic search of the literature was made to identify relevant reports of clinical trials of transdermal nicotine, followed by detailed statistical analysis of the results to calculate a pooled estimate of the rate of smoking cessation. Both a fixed effect and a random effects model were used to calculate pooled estimates.The pooled odds ratio (OR) for short-term smoking cessation in favour of the transdermal patches was OR=3.10. Using a random effects model, the risk difference (RD) in favour of the transdermal patches was RD=0.25. The corresponding values for long-term cessation were OR=2.26 and RD=0.11. Skin irritation was a common adverse effect with incidence rates ranging up to about 70%.Nicotine transdermal patches were effective in promoting smoking cessation both in the short-term, with assessments at 3 to 10 weeks, and in the long-term, with assessment at 24 to 52 weeks. Long-term abstinence rates in subjects treated with nicotine patches for a few weeks remained higher than in subjects treated with placebo patches. Adverse effects were usually minor and transient, although subjects with a sensitive skin may find the applications intolerable. Further studies are required to confirm the value of nicotine patches in promoting smoking cessation in the absence of professional medical support and in general medical practices in the community.     

The efficacy of computer-tailored smoking cessation material as a supplement to nicotine patch therapy

The study evaluated the efficacy of the Committed Quitters Program (CQP), a computer-tailored set of printed behavioral support materials offered free to purchasers of NicoDerm CQ patches, as a supplement to the nicotine patch and the standard brief User's Guide (UG) and audiotape. Callers to the CQP enrollment were randomized to either CQP (n=1854) or just the UG (n=1829). Abstinence and use of program materials were assessed by telephone interview at 6 and 12 weeks (the latter falling 2 weeks after patch use was to be discontinued). Considering all respondents, abstinence rates did not differ significantly between the UG and CQP groups. As expected, among those who reported they used their assigned materials (80.1% of the sample) smokers who received CQP demonstrated higher quit rates at both 6 weeks (38.8% v. 30.7%) and 12 weeks (18.2% v. 11.1%), compared to the UG group. Among those who used it, the Committed Quitters Program proved to be an effective behavioral treatment, improving quit rates over nicotine replacement therapy and a brief untailored written guide and audiotape.     

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     

Extended duration therapy with transdermal nicotine may attenuate weight gain following smoking cessation

Aim

People who quit smoking often gain 11–12 lb, on average, which can frequently lead to a relapse to smoking. This study evaluated whether extended vs. standard duration treatment with nicotine patch helps those able to quit smoking to reduce cessation-induced weight gain and explored nicotine patch adherence as a mediator of treatment effects.

Design and setting

We examined data from a completed randomized placebo-controlled clinical trial of extended (24 weeks) vs. standard (8 weeks plus 16 weeks of placebo) transdermal nicotine patch therapy. Changes in measured weight over 24 weeks were compared across the two treatment arms, controlling for gender, baseline smoking rate, and previous weight. Adherence to patch use was assessed using self-report of daily use over 24 weeks.

Participants

139 clinical trial participants who were confirmed to be abstinent at weeks 8 and 24.

Findings

Compared to participants who received 8 weeks of nicotine patch therapy, participants who received 24 weeks of treatment showed significantly less weight gain from pre-treatment to week 24 (β = −4.76, 95% CI: −7.68 to −1.84, p = .002) and significantly less weight gain from week 8 to week 24 (β = −2.31, 95% CI: −4.39 to −0.23, p = .03). Extended treatment increased patch adherence which, in turn, reduced weight gain; patch adherence accounted for 20% of the effect of treatment arm on weight gain.

Conclusion

Compared to 8 weeks of transdermal nicotine therapy, 24 weeks of patch treatment may help to reduce the weight gain that is typical among smokers who are able to achieve abstinence from tobacco use. Extended treatment increased nicotine patch adherence which, in turn, reduced weight gain.     

Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity

Rationale  

Smoking rates are up to five times higher in people with schizophrenia than in the general population, placing these individuals at high risk for smoking-related health problems. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, is a promising aid for smoking cessation in this population. To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia.     

Efficiency of multimodal smoking cessation therapy combining transdermal nicotine substitution with behavioral therapy

Effects of smoking cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in three studies. A total of 535 smokers underwent 9 weeks of behavioral self-control treatment. For 7 weeks, groups with transdermal nicotine substitution received in addition nicotine patches that continuously released nicotine through the skin into the circulatory system. The effects of treatment were measured by daily cigarette consumption. Subjects additionally treated with transdermal nicotine substitution reached significantly higher abstinence rates by the end of treatment and during the follow-up period than control subjects. The results thus indicate enhanced therapeutic effectiveness of transdermal nicotine substitution.     

Varenicline: new drug. Smoking cessation: no better than nicotine

(1) Drugs play a limited role in smoking cessation. Nicotine is the drug with the best risk-benefit balance and is available in several formulations and dose strengths. However, only about 16% of patients remain abstinent after one year, compared to about 10% of patients on placebo. Bupropion, an amphetamine derivative, is best avoided. (2) Varenicline, a partial acetylcholine receptor agonist, has been approved as an aid in smoking cessation. There are no published trials of varenicline versus nicotine. (3) Four placebo-controlled trials show that after 12 weeks of treatment with varenicline about 22% of patients remain abstinent at one year, compared to 8% on placebo. In the two trials also including a group treated with bupropion, the one-year abstinence rate was significantly higher with varenicline than bupropion in one trial and also in a combined analysis of the two trials. (4) The known adverse effects of varenicline seem to be limited in scope. In the short term they mainly consist of gastrointestinal problems (especially nausea and constipation) and neuropsychological disorders (insomnia, dream disturbances, and headache). Long-term cardiac toxicity cannot currently be ruled out. Simultaneous use of nicotine and varenicline aggravates the adverse effects of nicotine. (5) In practice, varenicline does not appear to have a better risk-benefit balance than nicotine. Nicotine therefore remains the first-choice drug when a patient needs pharmacological support to stop smoking.     

Meta-analysis of studies investigating one-year effectiveness of transdermal nicotine patches for smoking cessation.

PURPOSE: The one-year effectiveness of transdermal nicotine patches versus placebo patches for smoking cessation based on continuous or sustained abstinence was studied. METHODS: A literature search of MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials up to April 2006 was conducted. Articles containing relevant keywords were reviewed by two evaluators independently. To be considered for inclusion in the meta-analysis, studies had to be randomized clinical trials with a transdermal nicotine patch group and a placebo patch group, had to include at least one year of follow-up, had to have abstinence biochemically verified, and had to include the odds ratio (OR) as an outcome measure. RESULTS: Sixteen trials met the selection criteria. The total number of subjects was 9457 (6084 in the nicotine patch group and 3373 in the placebo patch group). The pooled OR for smoking abstinence at one year for the nicotine patch group versus the placebo patch group was 1.79 (95% confidence interval [CI], 1.55-2.08). The pooled OR for one-year continuous or sustained abstinence for the nicotine patch compared with placebo, excluding four studies reporting only point-prevalence abstinence, was 1.75 (95% CI, 1.49-2.05). CONCLUSION: A meta-analysis of trials of transdermal nicotine patch therapy versus placebo for smoking cessation yielded ORs for smoking abstinence of about 1.8 at one year after the start of therapy. ORs were similar whether the endpoint was point-prevalence abstinence, continuous or sustained abstinence, or both.     

Development of a novel prolonged-release nicotine transdermal patch.

A transdermal patch for delivering nicotine for periods of 12-48h was designed. An inclusion complex formed between the nicotine and beta-cyclodextrine (beta-CD) was used in drug depot. The usefulness of a specially cross-linked polyvinyl alcohol (cross-PVA) membrane was investigated as a rate controlling membrane. The influence of carbopol polymers, type C-934P and C-940 and propylene glycol on transdermal permeation of nicotine through the rat skin was investigated. The results indicated a maximum flux of 42 microgcm(-2)h(-1) after 48 h from the patches made from C-934P when the propylene glycol concentration was 15% and the nicotine-beta-CD mole ratio in the inclusion complex was 3:1. These nicotine transdermal patches can be fabricated to obtain a controlled release, zero order systems.     

Experience with a large-scale smoking cessation clinic

The experience of a large-scale smoking cessation clinic which was set up in conjunction with a mass media campaign, is described. The therapies employed were selected as suitable for use with large numbers of clients, could be self-applied and were suitable for short term programmes. Approximately one in four of those who attended at least one session reported they had ceased smoking. Hypnosis-assisted treatment was the least successful treatment. Overall compliance with the programme was low. The implication of these findings for future programmes is discussed.     

Varenicline for smoking cessation intervention in chronic obstructive pulmonary disease

INTRODUCTION: In smoking-related chronic obstructive pulmonary disease (COPD), smoking cessation was previously demonstrated to reduce lung function decline and disease morbidity if it resulted in a sustained tobacco abstinence. Varenicline is a newer pharmacologic therapeutic agent able to reduce withdrawal symptoms in smokers, and this makes it particularly valuable in inducing abstinence in patients with significant addiction. AREAS COVERED: This paper discusses the results of a randomized, placebo-controlled study evaluating the effects of a smoking cessation intervention including varenicline in patients with COPD. EXPERT OPINION: Varenicline can be an appropriate aid to maintaining smoking abstinence in patients with COPD and heavier nicotine addiction, and the documentation of the long-term effects of a smoking cessation intervention that includes this pharmacologic therapeutic agent is necessary.     

Varenicline for smoking cessation intervention in chronic obstructive pulmonary disease

Introduction: In smoking-related chronic obstructive pulmonary disease (COPD), smoking cessation was previously demonstrated to reduce lung function decline and disease morbidity if it resulted in a sustained tobacco abstinence. Varenicline is a newer pharmacologic therapeutic agent able to reduce withdrawal symptoms in smokers, and this makes it particularly valuable in inducing abstinence in patients with significant addiction.

Areas covered: This paper discusses the results of a randomized, placebo-controlled study evaluating the effects of a smoking cessation intervention including varenicline in patients with COPD.

Expert opinion: Varenicline can be an appropriate aid to maintaining smoking abstinence in patients with COPD and heavier nicotine addiction, and the documentation of the long-term effects of a smoking cessation intervention that includes this pharmacologic therapeutic agent is necessary.