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.     

Low-dose nicotine nasal spray use and effects during initial smoking cessation.

The purposes of this study were to determine if smokers wanting to quit smoking would use a low-dose nicotine nasal spray (i.e., acceptability) and what effect this spray use would have on withdrawal during the 1st week of cessation. Smokers (n?=? 52) were assigned double-blind to either placebo or nicotine spray (1.5 μg/kg. or approx. 0.1 mg, per spray) for ad lib use during the first week of cessation. All received group behavioral counseling. There was no difference in continuous 1-week abstinence (daily COa?     

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 nicotine patch in smoking cessation. A randomized trial with telephone counseling

BACKGROUND: This study was conducted to determine the efficacy of the nicotine patch in smoking cessation when combined with self-help materials, three brief visits, and telephone counseling. METHODS: One hundred fifty-nine healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking were enrolled in a double-blind trial with 6-week treatment and 6-month follow-up periods. After review of self-help materials, subjects were randomly assigned to regimens of nicotine or placebo patches. Subjects wore two patches per day for 4 weeks (25 mg of nicotine per 24 hours), then one patch per day for 2 weeks. Return visits were at the ends of weeks 4 and 6. Telephone counseling was given during weeks 1, 2, 3, and 5. Abstinence at 6 weeks was defined as zero cigarettes smoked for the previous 28 days, verified by exhaled carbon monoxide less than 8 ppm at 4 weeks and 6 weeks. Abstinence at 3 and 6 months was defined as self-report of zero cigarettes since the previous contact, verified by carbon monoxide value at 6 months. RESULTS: Abstinence rates at 6 weeks, 3 months, and 6 months were 29.5%, 21.8%, and 20.5% in the active group, and 8.8%, 3.8%, and 2.5% in the placebo group (P < or = .001 for each comparison), respectively. Skin irritation was the main side effect, causing 1.3% to drop out. CONCLUSION: The nicotine patch is efficacious in smoking cessation over a 6-month period, when combined with only self-help materials, three brief visits, and telephone counseling.     

The effect of five smoking cessation pharmacotherapies on smoking cessation milestones.

Objective: Most smoking cessation studies have used long-term abstinence as their primary outcome measure. Recent research has suggested that long-term abstinence may be an insensitive index of important smoking cessation mechanisms. The goal of the current study was to examine the effects of 5 smoking cessation pharmacotherapies using Shiffman et al.'s (2006) approach of examining the effect of smoking cessation medications on 3 process markers of cessation or smoking cessation milestones: initial abstinence, lapse, and the lapse–relapse transition. Method: The current study (N = 1,504; 58.2% female and 41.8% male; 83.9% Caucasian, 13.6% African American, 2.5% other races) examined the effect of 5 smoking cessation pharmacotherapy treatments versus placebo (bupropion, nicotine lozenge, nicotine patch, bupropion + lozenge, patch + lozenge) on Shiffman et al.'s smoking cessation milestones over 8 weeks following a quit attempt. Results: Results show that all 5 medication conditions decreased rates of failure to achieve initial abstinence and most (with the exception of the nicotine lozenge) decreased lapse risk; however, only the nicotine patch and bupropion + lozenge conditions affected the lapse–relapse transition. Conclusions: These findings demonstrate that medications are effective at aiding initial abstinence and decreasing lapse risk but that they generally do not decrease relapse risk following a lapse. The analysis of cessation milestones sheds light on important impediments to long-term smoking abstinence, suggests potential mechanisms of action of smoking cessation pharmacotherapies, and identifies targets for future treatment development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination

As part of a programme for the implementation of a Smoking Control Policy in our hospital, an open study, without randomization, of 65 hospital workers, who wanted to give up smoking, was carried out. The characteristics of smoking in each subject were recorded. The Fagerstrom Questionnaire was used to measure the degree of dependence on nicotine. The treatment consisted of the daily use of 16 h nicotine patches for 12 weeks. During the first 4 weeks, the patches contained 15 mg of nicotine, for the second 4 weeks, 10 mg, and for the last 4 weeks 5 mg (per patch and day). Five visits were scheduled during the 26 week study period: at the start of the study and after 4, 8, 12 and 26 weeks. The abstinence was checked by measuring carbon monoxide in end-expiratory air. The success rate was 31% after 12 weeks, and decreased to 29% after 26 weeks. In conclusion, the nicotine patches appeared safe and effective in this study.     

Nicotine patch and self-help video for cigarette smoking cessation.

A total of 424 smokers were randomized in a 2?×?2 factorial experiment. A pharmacologic factor contained 2 levels: transdermal nicotine patch (TNP; 21 mg) and placebo. A self-help behavioral treatment factor contained 2 levels: video-enhanced self-help treatment manual and self-help treatment manual only. At 2 months, TNP produced a higher level of abstinence (36%) than placebo (20%), p?     

Concurrent brief versus intensive smoking intervention during alcohol dependence treatment.

Alcohol dependent smokers (N=118) enrolled in an intensive outpatient substance abuse treatment program were randomized to a concurrent brief or intensive smoking cessation intervention. Brief treatment consisted of a 15-min counseling session with 5 min of follow-up. Intensive intervention consisted of three 1-hr counseling sessions plus 8 weeks of nicotine patch therapy. The cigarette abstinence rate, verified by breath carbon monoxide, was significantly higher for the intensive treatment group (27.5%) versus the rate for the brief treatment group (6.6%) at 1 month after the quit date but not at 6 months, when abstinence rates fell to 9.1% for the intensive treatment group and 2.1% for the brief treatment group. Smoking treatment assignment did not significantly impact alcohol outcomes. Although intensive smoking treatment was associated with higher rates of short-term tobacco abstinence, other, perhaps more intensive, smoking interventions are needed to produce lasting smoking cessation in alcohol dependent smokers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments

OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN: Two independent randomized placebo-controlled double-blind trials. SETTING: Smoking cessation clinic. SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS: Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.     

A systematic review of evidence for the appropriateness of neonatal screening programmes for inborn errors of metabolism

The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.     

Quitting chew: Results from a randomized trial using nicotine patches.

The authors examined the efficacy of transdermal nicotine replacement for cessation in 410 adult nonsmoking chewing tobacco users. Participants were randomly assigned to 6 weeks of 15-mg nicotine patch plus behavioral treatment or placebo patch plus behavioral treatment. All participants received the same behavioral treatment of 2 pharmacy visits, 2 support calls, and self-help materials. At 6 months after treatment, biochemically confirmed point-prevalence rates (no chewing in the last 7 days) in the active (38%) and placebo (34%) groups were high and not significantly different. The difference in relapse (no chewing for 7 consecutive days) between the active patch group (33%) and placebo group (48%) was significant at 6 months (p?=?.003). Nicotine dependence and age predicted nonrelapse at 6 months. The results suggest that nicotine replacement may improve chewers' chances of abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effectiveness of the 4-mg dose of nicotine polacrilex for the initial treatment of high-dependent smokers

PURPOSE: To determine the effectiveness of the 4-mg and 2-mg dosages of nicotine polacrilex vs placebo through the first 6 weeks of treatment (during which 75% of relapse occurs when there is no treatment) in assisting high-dependent smokers to stop smoking when instructed to use a fixed number (12 pieces) of medication daily. SUBJECTS AND METHODS: Ninety high-dependent (Fagerstr?m Tolerance Questionnaire score > or = 7 plus baseline carbon monoxide level > 15 ppm) healthy male and female smokers, highly motivated to quit smoking, were enrolled in a 6-week, randomized, double-blind, placebo-controlled trial in which they were instructed to use 12 pieces per day of their assigned dosage formulation: 4 mg, 2 mg, or 0.5 mg (placebo) of nicotine polacrilex. The behavioral intervention did not depend on providing any special psychological training, skills, or services but rather employed a standard medical practice model that could easily be implemented by any primary care physician. RESULTS: Sustained abstinence from weeks 2 through 6, determined at each visit by absolutely no cigarette use plus a carbon monoxide level of 8 ppm or lower was 59% (4-mg group), 30% (2-mg group), and 39% (placebo group) (P < .02). For the 55 of the 90 smokers who met the originally planned definition of high dependence (Fagerstr?m Tolerance Questionnaire score > or = 7 plus baseline smoking serum cotinine level > 250 ng/mL plus baseline carbon monoxide level > 15 ppm), results were 63% (4-mg group), 25% (2-mg group), and 25% (placebo group) (P < .02). In addition, the 4-mg dose produced statistically significantly higher abstinence rates in compliant subjects (P < .02) and also in subjects with high baseline serum continine levels who were compliant (P < .01) than did either the 2-mg dose or placebo. CONCLUSIONS: It appears that the 4-mg dose of nicotine polacrilex is the drug and dose of choice for the initial phase of tobacco dependence treatment in high-dependent smokers; the 2-mg dose of nicotine polacrilex is not better than placebo during the first 6 weeks of treatment for high-dependent cigarette smokers, and thus should not be used for these patients during the initial treatment phase.     

Analyzing milestones in smoking cessation: Illustration in a nicotine patch trial in adult smokers.

Tests of addiction treatments seldom reveal where treatment exercises its effect (i.e., promoting initial abstinence, preventing lapses, and/or impeding progression from lapse to relapse). The authors illustrate analyses distinguishing effects on these milestones in a randomized trial of high-dose nicotine patch (35 mg; n = 188) versus placebo (n = 136) in adult smokers, who used electronic diaries to monitor smoking in real time during 5 weeks of treatment. High-dose patch promoted initial abstinence (hazard ratio [HR] = 1.3) and decreased the risk of lapsing among those who achieved abstinence (HR = 1.6). The biggest effect of treatment was to prevent progression to relapse among those who had lapsed (HR = 7.1). Analysis of effects by milestones may enhance understanding of cessation treatments and their mechanisms of action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Nicotine–mecamylamine treatment for smoking cessation: The role of pre-cessation therapy.

The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n?=?20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5–5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CDK4, a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells

Rats infused subcutaneously with 9 mg/kg/day nicotine tartrate for 7 days exhibit behavioral abstinence signs following either termination of nicotine infusion or injection of the noncompetitive nicotinic antagonists mecamylamine (s.c.) or hexamethonium (ic.c.v.). This study examined the abstinence precipitating effects of dihydro-beta-erythroidine (DHbetaE), a competitive nicotinic antagonist. Twenty-four nicotine-dependent rats were injected in the third ventricle with 10, 18, or 25 microg DHbetaE in 20 microl saline or with saline alone and observed for abstinence signs over a 20-min period. There was a significant positive linear trend of overall abstinence signs as a function of dose, p < 0.01. In 12 nondependent rats, the high dose of DHbetaE did not induce more abstinence-like signs than saline alone. In a second experiment, 18 nicotine-dependent rats were injected s.c. with 1 or 6 mg/kg of the muscarinic antagonist scopolamine or with saline alone. Few abstinence signs were observed in any group: there was no significant drug effect. The results suggest that nicotine abstinence signs observed in the rat are specific to reduced stimulation of previously overstimulated nicotinic receptors.     

The sleep of abstinent pure primary alcoholic patients: natural course and relationship to relapse

Sleep in male pure primary alcoholic inpatients was examined at a mean of 16 days (n = 29), 19 weeks (n = 29), 14 months (n = 9), and 27 months (n = 4) of abstinence. Results were as follows: (1) the sleep of abstinent alcoholic patients is short, fragmented, and shallow early in abstinence; (2) a patient's sleep improves slowly over at least the first year of abstinence; however, (3) some facets of a patient's sleep remain abnormal even after 27 months of abstinence; (4) insomnia and sleep fragmentation after approximately 5 months of abstinence may be related to relapse by 14 months. The mechanism underlying the relationship between sleep and withdrawal in alcoholic patients is not well understood, and the issue of treating sleep problems as an adjunct to prevention of relapse warrants further investigation.     

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.     

The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.     

Biventricular repair in neonates with hypoplastic left heart complex

PURPOSE: We previously developed an inpatient regimen that consisted of infusional fluorouracil (5-FU), epirubicin, and cisplatin (ECisF), with a response rate of 86% in advanced breast cancer. The current phase II 2:1 randomized study investigated whether cyclophosphamide can be substituted for cisplatin (ECycloF) to reduce toxicity and allow the regimen to be administered on an outpatient basis without loss of efficacy. PATIENTS AND METHODS: Ninety-six women (median age, 49 years; range, 28 to 73) with breast cancer (59 metastatic, 37 locally advanced) received continuous infusional 5-FU (200 mg/m2/d via Hickman line) and six cycles of epirubicin (60 mg/m2 every 21 days) with either cyclophosphamide 600 mg/m2 every 21 days (38 metastatic, 24 locally advanced) or cisplatin 60 mg/m2 every 21 days (21 metastatic, 13 locally advanced). There were no significant differences in patient characteristics between these groups. RESULTS: ECycloF was better tolerated than ECisF in terms of lethargy (P = .005), stomatitis (P = .008), plantar palmar erythema (P = .02), constipation (P < .001), thrombosis (P = .0014), and nausea and vomiting (P = .05). Although there was a trend toward more anemia and leukopenia with ECisF (P =. 1), there was no significant difference in the rates of infection. Efficacy was comparable in terms of overall response (69% v 68%), complete response (CR; 13% v 15%), and median progression-free survival (9 v 8 months). CONCLUSION: ECycloF is an outpatient regimen with a lower incidence of severe nonhematologic toxicity than inpatient ECisF; it has comparable efficacy and is considerably more economical.