Placebo-controlled Smoking Cessation Trial Research Articles

Evaluating the effect of smoking cessation treatment on a complex dynamical system

ObjectiveTo understand the dynamic relations among tobacco withdrawal symptoms to inform the development of effective smoking cessation treatments. Dynamical system models from control engineering are introduced and utilized to evaluate complex treatment effects. We demonstrate how dynamical models can be used to examine how distinct withdrawal-related processes are related over time and how treatment influences these relations. MethodIntensive longitudinal data from a randomized placebo-controlled smoking cessation trial (N=1504) are used to estimate a dynamical model of withdrawal-related processes including momentary craving, negative affect, quitting self-efficacy, and cessation fatigue for each of six treatment conditions (nicotine patch, nicotine lozenge, bupropion, patch + lozenge, bupropion + lozenge, and placebo). ResultsEstimation and simulation results show that (1) withdrawal measurements are interrelated over time, (2) nicotine patch + nicotine lozenge showed reduced cessation fatigue and enhanced self-efficacy in the long-term while bupropion + nicotine lozenge was more effective at reducing negative affect and craving, and (3) although nicotine patch + nicotine lozenge had a better initial effect on cessation fatigue and self-efficacy, nicotine lozenge had a stronger effect on negative affect and nicotine patch had a stronger impact on craving. ConclusionsThis approach can be used to provide new evidence illustrating (a) the total impact of treatment conditions (via steady state values) and (b) the total initial impact (via rate of initial change values) on smoking-related outcomes for separate treatment conditions, noting that the conditions that produce the largest change may be different than the conditions that produce the fastest change.

Predictors of nicotine withdrawal symptoms: findings from the first randomized smoking cessation trial in a low-income country setting.

To identify predictors of nicotine withdrawal symptoms among smokers who participated in a randomized cessation trial in a low-income country. We analyzed data from 269 smokers who participated in a randomized, placebo-controlled smoking cessation trial conducted in primary healthcare in Aleppo, Syria. All participants received behavioral counseling and were randomized to receive either 6weeks of nicotine or placebo patch and were followed for one year. Throughout the study, lower total withdrawal score was associated with greater education (p=0.044), older age of smoking initiation (p=0.017), lower nicotine dependence (p=0.024), higher confidence in ability to quit (p=0.020), lower reported depression (p<0.001), higher adherence to patch (p=0.026), belief of receiving nicotine patches rather than placebo (p=0.011), and waterpipe use (p=0.047). Lower nicotine dependence, greater educational attainment, higher confidence in ability to quit and waterpipe use predict lower withdrawal severity. Waterpipe smoking may serve as a barrier to smoking cessation efforts in countries where its use is highly prevalent. Further, expectancies about the effects of pharmacotherapy appear to mediate the experience of nicotine withdrawal.

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

IntroductionThe development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. MethodsPredictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. ResultsOf the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. ConclusionAdherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages.

A test of the stress-buffering model of social support in smoking cessation: is the relationship between social support and time to relapse mediated by reduced withdrawal symptoms?

Social support has been linked to quitting smoking, but the mechanisms by which social support affects cessation are poorly understood. The current study tested a stress-buffering model of social support, which posits that social support protects or "buffers" individuals from stress related to quitting smoking. We hypothesized that social support would be negatively associated with risk of relapse, and that this effect would be mediated by reduced withdrawal and depressive symptoms (i.e., cessation-related stress) over time. Further, we predicted that trait neuroticism would moderate this mediational effect, such that individuals high in negative affectivity would show the greatest stress-buffering effects of social support. Participants were weight-concerned women (n = 349) ages 18-65 enrolled in a randomized, double-blind, placebo-controlled smoking cessation trial of bupropion and cognitive behavioral therapy. Social support was assessed at baseline, and biochemically-verified abstinence, withdrawal-related symptoms, and depressive symptoms were assessed at 1-, 3-, 6-, and 12-months follow-up. Social support was negatively related to risk of relapse in survival models and negatively related to withdrawal symptoms and depression in mixed effects models. These relationships held after controlling for the effects of pre-quit day negative affect and depression symptoms, assignment to treatment condition, and number of cigarettes smoked per day. A temporal mediation model showed that the effect of social support on risk of relapse was mediated by reductions in withdrawal symptoms over time but not by depression over time. Contrary to hypotheses, we did not find that neuroticism moderated this mediation effect. Increased social support may buffer women from the harmful effects of cessation-related withdrawal symptoms, which in turn improve cessation outcomes.

Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD

BackgroundTobacco withdrawal symptoms may be confounded with attention-deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD. Objective(1) To assess overlap between ADHD symptoms and tobacco/nicotine withdrawal symptoms and craving; (2) to assess the relationship between craving or withdrawal symptoms and the effect of osmotic-release oral system methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of ADHD symptoms, craving, and withdrawal symptoms with abstinence. MethodsSecondary analysis of a randomized, placebo controlled smoking cessation trial assessing the efficacy of OROS-MPH taken in addition to nicotine patch among individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were assessed at baseline and 2, 4 and 6 weeks after a target quit day. ResultsWithdrawal symptoms and craving showed limited and modest overlap with ADHD symptoms prior to abstinence but more extensive and stronger correlation after quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was attenuated by controlling for withdrawal symptoms, but not by craving. Craving, but not ADHD symptoms and withdrawal symptoms, was associated with abstinence during the trial. ConclusionWhen treating smokers with ADHD (1) craving, rather than tobacco withdrawal symptoms or ADHD symptoms may be the more effective therapeutic smoking cessation targets; (2) careful distinction of craving, withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is needed.

Smoking Cessation and Quality of Life: Changes in Life Satisfaction Over 3 Years Following a Quit Attempt

There has been limited research addressing changes in subjective well-being as a result of quitting smoking. The purpose of this study was to use longitudinal data to determine the relation between smoking cessation and subjective measures of well-being, including global quality of life (QOL), health-related QOL (HR-QOL), affect, relationship satisfaction, and stressor occurrence. As part of a randomized, placebo-controlled smoking cessation trial, 1,504 participants (58.2% women, 83.9% white) completed assessments and had their smoking status biochemically confirmed at baseline and years 1 and 3 post-quit. Compared with continuing smokers, quitters showed improved global QOL, HR-QOL, and affect at years 1 and 3 and fewer stressors by year 3. Smoking status did not influence marital relationship satisfaction. Successful quitters, in contrast to continuing smokers, reported improved subjective well-being, which could be used to motivate quit attempts by individuals with concerns about what life will be like without cigarettes.

Tobacco withdrawal components and their relations with cessation success

Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. This research was intended to provide information about two core components of withdrawal (negative affect and craving): (1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and (2) how these dimensions relate to cessation outcome. Adult smokers (N = 1,504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence. Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse. Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions.

Predictors of adherence to nicotine gum and counseling among African-American light smokers.

A high proportion of African-American smokers are light smokers, and they experience low smoking cessation rates and disproportionately high tobacco-related morbidity; yet no studies have examined tobacco treatment adherence in this group. To determine the predictors of adherence to nicotine gum and counseling among African-American light smokers (defined as smoking < or =10 cigarettes/day), and the effects of adherence on smoking cessation. Data were from a 2 x 2 randomized, placebo-controlled smoking cessation trial of nicotine gum (2 mg versus placebo) and counseling (motivational interviewing versus health education). Seven hundred fifty-five African-American light smokers at a community-based clinic. Demographic and health-related information, smoking behaviors, psychosocial variables, adherence to nicotine gum and counseling, and cotinine-verified 7-day abstinence from smoking at week-26 follow-up. A logistic regression model showed that having a higher body mass index (OR = 1.03, 95% CI = 1.01 to 1.05), more quit attempts in the past year (OR = 1.04, 95% CI = 1.01 to 1.07), higher baseline exhaled carbon monoxide (OR = 1.22, 95% CI = 1.01 to 1.48), and higher perceived stress (OR = 1.12, 95% CI = 1.03 to 1.22) increased the likelihood of adherence to nicotine gum. Being a high school graduate was a predictor of adherence to counseling (OR = 1.58, 95% CI = 1.02 to 2.44). Surprisingly, being adherent to nicotine gum significantly reduced the odds of smoking cessation (OR = 0.50, CI = 0.28 to 0.87). On the other hand, adherence to counseling dramatically increased the likelihood of smoking cessation (OR = 3.32, CI = 1.36 to 8.08). Individual risk factors may influence adherence to nicotine gum and counseling. Improving psychological interventions and promoting adherence to counseling may increase overall smoking cessation success among African-American light smokers.

Nurse-Conducted Smoking Cessation in Patients With COPD Using Nicotine Sublingual Tablets and Behavioral Support

Context Few studies have examined the effect of nicotine replacement therapy (NRT) in COPD patients. Study objective To evaluate the efficacy of nicotine sublingual tablets and two levels of support for smoking cessation in COPD patients. Design Double-blind, multicenter, placebo-controlled smoking cessation trial. Setting Pulmonary outpatient clinics. Patients Three hundred seventy COPD patients who smoked a mean of 19.6 cigarettes per day (mean, 42.7 pack-years; mean FEV1, 56% of predicted). Interventions Nicotine sublingual tablet or placebo for 12 weeks combined with either low support (four visits plus six telephone calls) or high support (seven visits plus five telephone calls) provided by nurses. Measurements Carbon monoxide-verified abstinence rates and St. George Respiratory Questionnaire (SGRQ) assessed at 6 months and 12 months. Results Two hundred eighty-eight of 370 patients were evaluable for the final study end points. Smoking cessation rates were statistically significantly superior with sublingual nicotine vs placebo for all measures of abstinence: 6-month point prevalence, 23% vs 10%; 12-month point prevalence, 17% vs 10%. There was no significant difference in effect between low vs high behavioral support. The SGRQ score improved significantly in abstainers vs nonabstainers; the changes in mean scores were –10.9 vs – 2.9 for total score, and – 28.6 vs − 2.3 for symptom score, respectively. Conclusions This trial demonstrated the long-term efficacy of NRT for cessation for the general population of COPD smokers, regardless of daily cigarette consumption. Cessation success rates were in the same range as in healthy smokers, and abstinence improved SGRQ scores. NRT should be used to aid cessation in all smokers with COPD, regardless of disease severity and number of cigarettes smoked. Few studies have examined the effect of nicotine replacement therapy (NRT) in COPD patients. To evaluate the efficacy of nicotine sublingual tablets and two levels of support for smoking cessation in COPD patients. Double-blind, multicenter, placebo-controlled smoking cessation trial. Pulmonary outpatient clinics. Three hundred seventy COPD patients who smoked a mean of 19.6 cigarettes per day (mean, 42.7 pack-years; mean FEV1, 56% of predicted). Nicotine sublingual tablet or placebo for 12 weeks combined with either low support (four visits plus six telephone calls) or high support (seven visits plus five telephone calls) provided by nurses. Carbon monoxide-verified abstinence rates and St. George Respiratory Questionnaire (SGRQ) assessed at 6 months and 12 months. Two hundred eighty-eight of 370 patients were evaluable for the final study end points. Smoking cessation rates were statistically significantly superior with sublingual nicotine vs placebo for all measures of abstinence: 6-month point prevalence, 23% vs 10%; 12-month point prevalence, 17% vs 10%. There was no significant difference in effect between low vs high behavioral support. The SGRQ score improved significantly in abstainers vs nonabstainers; the changes in mean scores were –10.9 vs – 2.9 for total score, and – 28.6 vs − 2.3 for symptom score, respectively. This trial demonstrated the long-term efficacy of NRT for cessation for the general population of COPD smokers, regardless of daily cigarette consumption. Cessation success rates were in the same range as in healthy smokers, and abstinence improved SGRQ scores. NRT should be used to aid cessation in all smokers with COPD, regardless of disease severity and number of cigarettes smoked.

Combined Agonist-Antagonist Treatment for Nicotine and Other Drug Dependencies

Co-administration of an agonist with an antagonist may regulate receptor activation, resulting in relief of withdrawal symptoms and blockade of drug reward. In one study, 12 smokers rated the rewarding effects of cigarette smoke after separate and combined administration of nicotine and the nicotinic antagonist mecamylamine. While each drug offset potential side effects of the other, they acted in unison to attenuate smoking reward. In a second study, 48 subjects participated in a randomized, double-blind, placebo-controlled smoking cessation trial. Nicotine skin patch therapy (21 mg/day for 6-8 weeks) + oral mecamylamine (2.5-5 mg b.i.d. for 5 weeks) was compared to nicotine patch + placebo. Mecamylamine treatment began two weeks before smoking cessation. Combined agonist-antagonist treatment produced significantly higher continuous smoking abstinence than agonist-alone treatment: 50% vs 16.7% at seven weeks (p=.015), 37.5% vs 12.5% at six months (p=.046) and 37.5% vs 4.2% at twelve months (p=.004). Concurrent agonist-antagonist treatment may prove useful in treating other drug dependencies, and has potential advantages over treatment using agonists alone, antagonists alone or partial agonists.

Effects of fluoxetine on weight gain and food intake in smokers who reduce nicotine intake

The effect of fluoxetine hydrochloride, a 5-HT uptake inhibitor (60 mg/day PO), in preventing weight gain associated with nicotine reduction was investigated in participants in a double-blind, placebo-controlled smoking-cessation trial. A lunch of cheese pizza and chocolate bars was offered, and caloric intake was monitored. The analysis focused on subjects (placebo: n=11; fluoxetine: n=10) who succeeded in reaching cotinine levels of less than 50% of their starting cotinine levels (signifying a stringent reduction in nicotine intake) and who participated in pre- and post-nicotine reduction lunch sessions 70 days apart. Subjects on placebo gained significantly more weight (mean±SEM = +3.3±0.7 kg) than subjects on fluoxetine (−0.6±1.2 kg). In fluoxetine-treated subjects, weight gain/loss was strongly correlated with initial body mass index, with higher BMI being associated with greater decreases in weight. A trend towards decreased caloric intake in the fluoxetine group was observed; the change in total calories at lunch was significantly correlated with weight change, an association accounted for principally by change in pizza intake. We conclude that fluoxetine treatment effectively prevents the weight gain that accompanies nicotine reduction and that this phenomenon is mediated, at least in part, by diminished caloric intake.