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.     

Intraoperative injury to the spleen--organ preservation at any price?

This study evaluated serum nicotine and sensory differences of five different doses of nicotine polacrilex (0.0, 0.5, 1.0, 2.0 and 4.0 mg nicotine), three of which have been used as placebo doses in clinical trials (0.0, 0.5, and 1.0 mg) and two of which are currently available as pharmacologic treatments for smoking cessation (2.0 or 4.0 mg nicotine). Twenty-one smokers received, on different days and in random order, five pieces of each of the five doses of polacrilex. The objective of the study was to evaluate whether consistent serum nicotine and sensory differences would be observed between the doses. After 5 h use, the 0.0, 0.5, 1.0, 2.0, and 4.0 mg doses produced the following results: (1) there was a linear trend across the placebo doses of nicotine polacrilex in serum nicotine and nicotine flavor, although pairwise dose comparisons were not significant, (2) the 0.0 and 0.5 mg placebo doses resulted in serum nicotine and sensory ratings that were significantly different from the 2.0 mg dose, and even more so from the 4.0 mg dose, (3) the 1.0 mg dose was not different from the 2.0 mg dose on serum nicotine level and several sensory characteristics, though it was different from the 4.0 mg dose on both, and (4) the 4.0 mg dose resulted in significantly higher serum nicotine and usually higher sensory ratings than the 2.0 mg dose. Since the 0.0 mg placebo achieves sensory effects that are comparable to the nicotine-containing placebo doses, it is recommended over the 0.5 and 1.0 mg doses as the nicotine polacrilex placebo of choice in most clinical trials.     

Nicotine gum dose and weight gain after smoking cessation.

The authors examined weight gain in 79 abstinent cigarette smokers during treatment with placebo or with 2 mg or 4 mg of nicotine gum. Results indicated that nicotine gum suppressed weight gain in a linear fashion with increasing nicotine dose. At 90 days postcessation, placebo gum users gained 3.7 kg, 2-mg gum users gained 2.1 kg, and 4-mg gum users gained 1.7 kg. Assessment of nicotine replacement by means of pre- and postcessation salivary cotinine levels revealed that smokers who replaced a greater percentage of their baseline cotinine levels during treatment gained less weight. Percentage of baseline cotinine replaced remained related to weight gain after the number of pieces of gum used was controlled. Implications for smokers hoping to minimize postcessation weight gain are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of sustained-release bupropion and placebo for smoking cessation

BACKGROUND AND METHODS: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. RESULTS: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. CONCLUSIONS: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.     

High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 × 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transdermal clonidine for smoking cessation: A double-blind randomized dose–response study.

A 4-week trial tested the effects of 4 doses (placebo, 0.1 mg/d, 0.2 mg/d, and 0.3 mg/d) of transdermal clonidine on smoking cessation and nicotine withdrawal. After a 1-week baseline, smokers (N?=?72) started the drug and tried to quit by Week 3. Significantly fewer smokers who received a placebo were abstinent at 5 days after quitting as compared with smokers who received clonidine at any dose (19% vs 57%, respectively, p?=?.007). Blood clonidine concentration interacted with nicotine dependence (p?     

Effectiveness of Payment for Reduced Carbon Monoxide Levels and Noncontingent Payments on Smoking Behaviors in Cocaine-Abusing Outpatients Wearing Nicotine or Placebo Patches.

In a 2-week intervention to reduce cigarette smoking among outpatients in treatment for cocaine addiction, 20 subjects were randomly assigned to a contingent group, receiving monetary vouchers for breath samples with carbon monoxide (CO) levels of 8 ppm or less, or to a noncontingent group, receiving vouchers regardless of CO level. Subjects wore either nicotine or placebo patches in a randomized crossover design. Contingent subjects had significantly lower CO levels and met the 8 ppm target significantly more often than did noncontingent subjects; however, number of cigarettes reported smoked did not differ between groups. Use of nicotine patches resulted in CO levels significantly lower than did use of placebo patches, but levels still exceeded 8 ppm regardless of type of patch. Because contingent reward helped cocaine-dependent smokers achieve nonsmoking CO targets, behavioral antismoking interventions merit continued study in similar populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral treatment for smokers with a history of alcoholism: Predictors of successful outcome.

This study examined baseline predictors associated with smoking abstinence among 205 smokers (113 men, 92 women) with a past history of alcoholism. Their mean age was 41.8 years, and 93% were Caucasian. Participants were randomly assigned to standard treatment (ST), behavioral counseling plus exercise (BEX), or behavioral counseling plus nicotine gum (BNIC). Factors multivariately associated with point-prevalence smoking abstinence at posttreatment (1 week after target quit date) were a longer duration of prior smoking abstinence and an interaction between treatment group and having an active 12-step sponsor. ST was more effective for those with an active sponsor, whereas both BEX and BNIC were more effective for those without an active sponsor. At 1-year follow-up, independent predictors of point-prevalence smoking abstinence were a lower Fagerstr6m Tolerance Questionnaire score (K. O. Fagerstrom, 1978) and fewer years of smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

B-mode-guided vector-A-mode versus A-mode biometry to determine axial length and intraocular lens power

Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group (N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 +/- 149 ng/ml) were similar to those in continuing smokers (290 +/- 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 +/- 276 ng/ml), NG-using smokers (309 +/- 240 ng/ml), and NG-non-using smokers (311 +/- 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.     

Nicotine gum and behavioral treatment: A placebo controlled trial.

Subjects (N?=?139) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2?×?2 factorial design. The 2-mg gum produced higher abstinence rates than did the placebo. Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks (56% abstainers) and 52 weeks (50% abstainers). Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower, but this relation was nonsignificant. The results of this study are compared with an earlier nonblind trial. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do heavy smokers benefit from higher dose nicotine patch therapy?

Heavy smokers (N?=?408, smoking more than 25 cigarettes/day) were randomized to receive high-dose (25 mg) or standard-dose (15 mg) nicotine patch therapy delivered during the daytime only (16 hr) for a period of 6 weeks. Treatment effects of each dose were similar. The percentages of participants not smoking at 2-, 6-, and 12-month follow-ups were 26 versus 20, 14 versus 16, and 14 versus 14 for the 15-mg and 25-mg doses, respectively. The higher dose was well tolerated, and adverse event profiles for both treatment doses were very similar. Stepwise Cox proportional hazards analyses indicated that initial postrandomization craving and baseline scores on the Center for Epidemiological Studies Depression Instrument predicted time-to-relapse during treatment; only initial craving predicted relapse over the entire study interval (12 months). The results of this trial do not support the routine use of higher dose nicotine patch therapy in the treatment of nicotine dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Bupropion on Depression Symptoms in a Smoking Cessation Clinical Trial.

Bupropion is an antidepressant shown to be efficacious for smoking cessation. This study examined the short- and long-term effects of bupropion (300 mg/day for 10 weeks) versus placebo on depression symptoms among 497 smokers attempting to quit in a randomized trial of bupropion plus behavioral counseling. Depression symptoms were assessed via the Center for Epidemiological Studies Depression Scale (L. Radloff, 1977) at baseline, end of treatment, and at 6-month follow-up. Baseline nicotine dependence level was assessed with the Fagerstrom Test for Nicotine Dependence (T. F. Heatherton, L. T. Kozlowski, R. C. Frecker, & K. O. Fagerstr?m, 1991). A regression model of depression symptoms demonstrated a significant interaction between nicotine dependence and treatment for the treatment phase and during follow-up. Depression symptoms did not mediate the effects of bupropion on abstinence at either time point. Highly nicotine-dependent smokers who receive bupropion are more likely to experience a decrease in depressive symptoms during active treatment but are also more likely to experience a rebound in depressive symptoms when bupropion is discontinued. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

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)     

Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety and Smoking Cues in College Smokers.

In a 2 (patch) × 2 (smoking) × 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch × Smoking × Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Depression and smoking cessation: Characteristics of depressed smokers and effects of nicotine replacement.

Previous research has linked depression to difficulties in smoking cessation. The authors followed 269 smokers who attempted to quit smoking for 3 months. Participants were given nicotine gum (2 or 4 mg) or placebo gum and brief counseling. The study found that 34% of the smokers met the criterion for current depression using the Center for Epidemiological Studies Depression Scale. Depressed smokers relapsed significantly earlier than the nondepressed. Nicotine gum was significantly more effective than placebo gum among all smokers. The benefits of nicotine gum were particularly apparent among the depressed. Only 12.5% of depressed smokers quit successfully with placebo gum for 3 months, whereas 29.5% quit with nicotine gum. Depressed smokers reported more stress, less coping resources, more physical and psychological symptoms, and more frequent smoking in the presence of negative affect than did the nondepressed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context modulated effects of nicotine abstinence on human cooperative responding.

The effects of ad libitum smoking, abstinence, and 0-, 2-, and 4-mg nicotine gum on human cooperative responding were examined in 10 male and female tobacco smokers (aged 21–39 yrs). Participants were provided the opportunity to respond cooperatively or independently to episodes initiated by a computer-simulated other person. Participants could also initiate episodes that ostensibly provided the other person the opportunity to respond cooperatively or independently of the participant. Working cooperatively added points to both the participant's and other person's counters. Working independently added points only to the participant's counter. Results showed that abstinence decreased cooperative responses during episodes initiated by the computer-stimulated other person. Relative to abstinence and placebo gum conditions, ad libitum smoking and administration of 2- and 4-mg nicotine gum increased these cooperative responses. Nicotine increased reports of vigor and decreased abstinence-engendered reports of depression, anger, confusion, and tension. The difference in the effects of nicotine abstinence on the 2 classes of cooperative responding demonstrates that the social contingency mediates the behavioral effects of abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2×2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prospective evaluation of three smoking interventions in 205 recovering alcoholics: One-year results of Project SCRAP-Tobacco.

205 (113 male, 92 female) nonhospitalized recovering alcoholics with >3 mo of continuous abstinence from alcohol and drugs and relatively heavy tobacco dependence (Fagerstrom Tolerance Questionnaire score?=? 7.7; mean number of cigarettes per day, 26.8; mean number of years smoked, 24.4) were randomized to standard treatment (ST) American Lung Association quit program plus nicotine anonymous meetings (n?=?70), behavioral counseling plus physical exercise (BEX; n?=?72), or behavioral counseling plus nicotine gum (BNIC; n?=?63). A 3?×?4 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline, posttreatment, and 6- and 12-mo follow-ups. Self-reported smoking status was verified with biochemical and informant report. Verified self-report indicated that significantly more smokers in BEX quit by posttreatment (60%) than in either BNIC (52%) or ST (31%), χ–2(2, N?=?205)?=?17.85, p?