Effect of nicotine nasal spray on smoking cessation. A randomized, placebo-controlled, double-blind study

BACKGROUND: Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all smokers can use the nicotine gum or nicotine patch owing to side effects. In addition, the absorption of nicotine from these formulas is slow compared with smoking. A nicotine nasal spray delivers nicotine more rapidly. The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation. METHODS: Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren's Hospital, G?teborg, Sweden. Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks. At their first group session, subjects were randomized to a group receiving nicotine spray (n = 125), 0.5 mg of nicotine per single spray, or to a placebo group (n = 123). The procedure was double blind. Success rates were measured up to 12 months. The nonsmoking status was verified by expired carbon monoxide less than 10 ppm. RESULTS: Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group (27% vs 15%; odds ratio, 2.16; 95% confidence interval, 1.15 to 4.12). Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year. Mild or moderate side effects were rather frequent for both sprays, but they were significantly more for the nicotine spray. Subjects with high scores (> 7) on Fagerstr?m's tolerance questionnaire had a significantly lower success rate with placebo than with the nicotine spray. For subjects with low scores, there was no difference. CONCLUSION: Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation.     

Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation

BACKGROUND: This study uses wrist actigrapy to assess the effects of 24-hr transdermal nicotine replacement on the sleep and daytime activity of smokers during smoking cessation. METHODS: Seventy-one subjects grouped as light (n = 23), moderate (n = 24), or heavy (n = 24) smokers were randomly assigned to placebo or 11, 22, or 44 mg/day doses of transdermal nicotine for 1 week of intensive inpatient treatment of nicotine dependence. Outpatient patch therapy continued for 7 weeks following the inpatient stay. Those initially on placebo were randomly assigned to 11 or 22 mg/day, and those initially on 44 mg/day were reduced to 22 mg/day at Week 4. RESULTS: There was a significant decrease in daytime wrist activity during patch therapy and the 1st week off patch therapy. These changes in daytime wrist activity were positively correlated with percentage of nicotine and cotinine replacement. No changes from baseline in sleep (sleep efficiency or wrist activity) were detected, nor were there differences in sleep among the four patch doses. CONCLUSIONS: Using wrist actigraphy, this study failed to show any disturbing effects of 24-hr high-dose nicotine replacement on sleep. Lower levels of nicotine replacement were associated with a decrease from baseline in daytime wrist activity.     

Effects of behavioral and pharmacological treatment on smokeless tobacco users.

The purpose of this study was to examine the effects of 2 mg of nicotine polacrilex versus placebo gum and of group behavioral treatment versus minimal contact on cessation of smokeless tobacco use. Participants (N?=?210) were randomly assigned 1 of the 4 treatment conditions. Withdrawal symptoms were assessed throughout the treatment. Follow-up assessments were made at 1, 6, and 12 months posttreatment. Survival curve analysis showed that any of the 3 treatment groups involving group behavioral therapy or placebo gum were equally effective and superior to the minimal contact plus 2 mg of nicotine gum treatment in terms of abstinence. On the other hand, withdrawal symptoms were significantly reduced by nicotine gum, compared with placebo during the initial phases of cessation. The ineffectiveness of nicotine gum on treatment outcome may be attributed to its similarity with smokeless tobacco. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Addressing heavy drinking in smoking cessation treatment: A randomized clinical trial.

Heavy alcohol use frequently co-occurs with cigarette smoking and may impede smoking cessation. This clinical trial examined whether smoking cessation treatment that incorporates brief alcohol intervention can improve smoking cessation outcomes (7-day verified point prevalence abstinence) and reduce drinks consumed per week. Heavy drinkers seeking smoking cessation treatment were assigned by urn randomization to receive, along with 8 weeks of nicotine replacement therapy, either a 4-session standard smoking cessation treatment (ST, n = 119) or standard treatment of equal intensity that incorporated brief alcohol intervention (ST-BI, n = 117). Across follow-ups over 26 weeks, participants in ST-BI reported approximately 20% fewer drinks per week (p     

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up

OBJECTIVE: To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year. DESIGN: Placebo controlled, double blind trial. SETTING: Reykjavik health centre. SUBJECTS: 237 smokers aged 22-66 years living in or around Reykjavik. INTERVENTIONS: Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment. MAIN OUTCOME MEASURE: Sustained abstinence from smoking. RESULTS: Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected]. CONCLUSIONS: Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.     

Hostility and smoking cessation treatment outcome in heavy social drinkers.

Hostility is a multifaceted construct encompassing affective, behavioral, and cognitive aspects. There is preliminary evidence linking hostility to poorer outcomes in smoking cessation treatment; however, it is unclear which components of hostility are most important in cessation. In this study, the authors examined multiple aspects of trait hostility in 92 heavy social drinkers who were seeking smoking cessation treatment. Consistent with their hypothesis, the authors found that the cognitive component of hostility was most relevant to smoking cessation outcome. Specifically, those who expressed bitterness about their lives and tended to believe that they had poor luck and had gotten a raw deal out of life had poor smoking cessation outcomes. Cognitive measures of hostility also predicted greater nicotine withdrawal symptoms 1 week after quitting smoking. Other components of hostility including anger and both physical and verbal aggression did not significantly predict smoking outcome or nicotine withdrawal. Further examination of how a hostile worldview contributes to smoking cessation failure is warranted, as this facet of hostility may prove a valuable target for smoking cessation interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facial EMG as an index of affective response to nicotine.

Negative affect reduction has been postulated to be a key feature of cigarette smoking. In the present study, facial electromyography (EMG), heart rate (HR), and skin conductance response (SCR) were used to evaluate the affective significance of acute nicotine administration and overnight withdrawal. Smokers (N = 115) attended four 90-min laboratory assessment sessions scheduled approximately 3 days apart. The sessions provided a complete crossing of 2 prelaboratory deprivation conditions (12-hr deprived vs. nondeprived) with 2 drug conditions (nicotine vs. placebo nasal spray). During each session, smokers viewed affective slides while facial EMG, HR, and SCR were recorded. Results indicated that for women, nicotine nasal spray resulted in lower corrugator EMG activity during both smoking-deprived and nondeprived sessions, compared with placebo. However, nondeprived women also showed an increase in zygomaticus EMG when given nicotine compared with placebo spray, whereas smoking-deprived women demonstrated a decrease in the zygomaticus response to nicotine compared with placebo. With men, nicotine also appeared to lower corrugator during deprivation, but not nondeprivation, compared with placebo spray, though the contrast only approached significance. With zygomaticus EMG, nicotine spray decreased men's zygomaticus responding during nondeprivation but not during deprivation, compared with placebo spray. The HR results reflected the stimulatory properties of the drug rather than nicotine's affective properties, whereas SCR was unresponsive to our experimental manipulations. The corrugator EMG results support negative reinforcement models of smoking that postulate that acute nicotine use reduces withdrawal-driven negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Silver acetate interactions with nicotine and non-nicotine smoke components.

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strike while the iron is hot: Can stepped-care treatments resurrect relapsing smokers?

The efficacies of 2 group counseling step-up treatments for smoking cessation, cognitive-behavioral/skill training therapy (CBT) and motivational interviewing/supportive (MIS) therapy, were compared with brief intervention (BI) treatment in a sample of 677 smokers. Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse (no smoking vs. any smoking during the first postquit week, respectively). All participants received 8 weeks of nicotine patch therapy. BI consisted of 3 brief individual cessation counseling sessions; CBT and MIS participants received BI treatment and 6 group counseling sessions. Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI. Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT. Other hypotheses were not supported. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of antidepressant pharmacotherapy on behavioral treatment adherence and smoking cessation outcome in a combined treatment involving fluoxetine.

The authors examined whether serum fluoxetine levels influence behavioral treatment adherence and smoking cessation outcome. Nondepressed smokers (N?=?989) from 16 centers were randomized on a double-blind basis to receive either fluoxetine (30 or 60 mg) or placebo plus 9 sessions of behavioral smoking cessation treatment. Fluoxetine and norfluoxetine blood levels were assayed 1 week after the quit date. Logistic regression was used to predict treatment completion and cessation outcome, controlling for gender, age, treatment site, and degree of nicotine dependence. Higher steady-state fluoxetine blood levels (fluoxetine?+?norfluoxetine) predicted less likelihood of dropping out, χ2(1, N?=?820)?=?3.9, p?N?=?513)?=?18.1, p?     

Three year continuous abstinence in a smoking cessation study using the nicotine transdermal patch

A total of 305 subjects from Sydney were randomly allocated to receive either an active (24 hour transdermal nicotine patch over a 10 week course) or placebo nicotine patch. All subjects participated in a multicomponent cognitive-behavioural smoking cessation programme over five weeks in two-hour group sessions. The continuous abstinence rates at three years (validated by expired carbon monoxide) were 13.8% for the active group and 5.2% for placebo group (p = 0.011). The active nicotine patch with behavioural therapy achieved more than double the abstinence rates early in treatment compared with placebo and this difference was maintained throughout the three year follow up.     

The effect of anticipatory strategies on the first day of smoking cessation.

The authors tested a model hypothesizing the predictors and the effects of anticipatory strategy use on the 1st day of smoking cessation using data from 63 participants in an ecological momentary assessment study of smoking cessation. Remaining abstinent on the 1st day of cessation was not associated with mean level of urges to smoke during tempting situations but was associated with anticipatory strategy use, which accounted for 18% of the variance. Getting rid of cigarettes contributed the most to this effect (β?=?-.397). Getting rid of cigarettes was itself predicted by 2 variables, lower nicotine dependence (β?=?-.264) and attending a formal smoking cessation class (β?=?.305), which accounted for 15% of its variance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contingency management for smoking cessation in adolescent smokers.

This pilot study evaluated the use of contingency management (CM) procedures in combination with cognitive-behavioral therapy (CBT) for smoking cessation in adolescents. Twenty-eight treatment-seeking adolescent smokers participated in a 1-month, school-based smoking cessation program and were randomly assigned to receive either CM with weekly CBT or CBT alone. In the CM+CBT group, biochemical verification of abstinence was obtained twice daily during the first 2 weeks, followed by daily appointments during the 3rd week and once every other day during the 4th week. Participants were monetarily reinforced for abstinence on an escalating magnitude schedule with a reset contingency. At the end of 1 week and 1 month of treatment, abstinence verified using quantitative urine cotinine levels was higher in participants in the CM+CBT group (1 week: 76.7%; 1 month: 53.0%) when compared with the CBT-alone group (1 week: 7.2%; 4 weeks: 0%). These preliminary results provide a strong initial signal supporting the utility of CM techniques for smoking cessation in adolescents and demonstrate the feasibility of implementing such a program in a school setting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotine replacement: Effects on postcessation weight gain.

Examined nicotine replacement effects on postcessation weight gain in smoking cessation clinic volunteers using objective indices of cigarette smoking, gum use, and body weight. After they achieved abstinence, subjects were randomly assigned to either active nicotine or placebo gum conditions for 10 weeks, during which smoking status was carefully monitored. Analyses revealed strong evidence for a gum effect on weight gain, with active gum users gaining a mean total of 3.8 lbs compared with 7.8 lbs for placebo gum users at the end of the 10-week trial. Evidence for a dose–response relation was found, suggesting that more gum use (≥6.5 pieces/day) resulted in greater weight suppression. Placebo gum subjects reported greater postcessation increases in eating and hunger compared with active gum subjects. The implications of the weight suppression effect of nicotine gum for smoking cessation treatments are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of transdermal nicotine on digital perfusion in reformed habitual smokers

The effects of transdermal nicotine-assisted smoking cessation on digital perfusion and health-related quality of life were assessed in 10 chronic smokers. Components of digital blood flow were evaluated by digital temperature and laser Doppler fluxmetry before, during, and after a standardized cold challenge. Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion profile was obtained by laser Doppler perfusion imaging. A battery of validated measures were used to evaluate health-related quality of life. The microvascular response of smokers was evaluated before smoking cessation and at 2 and 7 days after smoking cessation and was compared with the response of nonsmoking controls. Results demonstrated that a (1) cutaneous microvascular perfusion was lower in smokers than nonsmokers, (2) the acute administration of transdermal nicotine did not decrease cutaneous perfusion, (3) smoking cessation and transdermal nicotine normalized digital microvascular perfusion by 7 days, and (4) transdermal nicotine and smoking cessation did not negatively impact health-related quality of life.     

An open trial of transdermal nicotine replacement therapy for smoking cessation among alcohol- and drug-dependent inpatients

An open trial of transdermal nicotine replacement for smoking cessation was conducted. Over a 7-month period, all patients admitted to the inpatient alcohol and drug treatment unit of the Seattle Veterans Affairs Medical Center, (n = 207) were offered the opportunity to participate in an open trial of transdermal nicotine replacement for smoking cessation. Forty-nine (23.7%) elected to attempt cessation with transdermal nicotine during their inpatient treatment episodes. These subjects received no psychosocial treatments directed specifically at smoking cessation. They smoked a mean of 28.5 (SD = 16.4) cigarettes per day and obtained a mean score of 8.3 (SD = 1.9) on the Fagerstrom Test for Nicotine Dependence. Subjects remained on transdermal nicotine an average of 18.8 (SD = 8.2) days with desire to resume smoking the major reason for discontinuation. Seven subjects (14.3%) self-reported tobacco abstinence at 21 days, and 5 (10.2%) self-reported abstinence as outpatients at 6 weeks. These results show that a substantial proportion of alcohol- and drug-dependent patients entering inpatient treatment are willing to attempt alcohol and illicit drug cessation and tobacco cessation simultaneously and that transdermal nicotine holds promise as a treatment modality in this population.     

Identifying individuals with high fat levels and low P:S ratios, in their diets, for intensive dietary intervention

OBJECTIVE: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. METHODS: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. RESULTS: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. CONCLUSION: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment-particularly for high dose regimens (> 22 mg per 24 hours).     

The nicotine inhaler in smoking cessation

BACKGROUND: Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation. OBJECTIVES: To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS: Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.     

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measures of affect and nicotine dependence predict differential response to smoking cessation treatments.

126 smokers were randomly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies (skills training or support) and 1 of 2 nicotine exposure strategies (nicotine gum or rapid smoking). Counseling and nicotine strategies were completely crossed: All 4 combinations resulted in equivalent 1-yr abstinence rates. Skills training produced higher initial cessation and more coping responses posttreatment than did support. Rapid smoking, but not nicotine gum, produced tachycardia to the taste of cigarettes posttreatment, consistent with cigarette aversion. The treatments were differentially effective among subpopulations of smokers: Ss high in pretreatment negative affect responded best to support counseling; those low in pretreatment negative affect responded best to skills training. Self-reports of pretreatment craving predicted response to the nicotine-exposure treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)