Pooled analysis of three randomized, double-blind, placebo controlled trials with rimonabant for smoking cessation.

Despite the withdrawal of CB1 antagonists, such as rimonabant, from the market and from active clinical development because of concerns about their side effect profiles, research suggests that the endocannabinoid system may play an important role in modulating nicotine's effects. We report the combined results, using a pooled analysis, of three previously unpublished trials assessing rimonabant as a smoking cessation pharmacotherapy conducted between 2002 and 2004. Smokers (n = 2097) motivated to quit were enrolled in three randomized, double-blind, placebo-controlled trials, STRATUS EU, US, and META, which consisted of a 10-week treatment period with either rimonabant 20 mg (n = 789), 5 mg (n = 518; used in only two of the three studies), or placebo (n = 790), in conjunction with brief counseling. The impact of drug on prolonged abstinence and adverse events was examined at 8 weeks (end-of-treatment) and at 48 weeks (available for STRATUS EU and US) after the targeted quit date. Rimonabant 20 mg resulted in significantly higher abstinence at end-of-treatment and at 48 weeks post-targeted quit date compared with placebo, while rimonabant 5 mg and placebo did not differ. Serious AEs did not differ by drug group. The 20 mg rimonabant dose, compared with placebo, produced increased nausea, diarrhea, anxiety symptoms, hyporexia, and vomiting, and decreased headache, constipation, and cough. These results support rimonabant 20 mg as a modestly effective aid for smoking cessation. Although work on CB1 antagonists such as rimonabant has mostly been stopped because of unacceptable adverse events, these results may inform and spur the development of other endocannabinoids for smoking cessation.

Clinician-delivered intervention to facilitate tobacco quitline use by surgical patients.

BACKGROUND: Telephone quitlines that provide counseling support are efficacious in helping cigarette smokers quit and have been widely disseminated; currently, they are underused. Surgery represents a teachable moment for smoking cessation, which can benefit surgical outcomes; however, few surgical patients receive smoking cessation interventions. This study developed and tested a clinician-delivered intervention to facilitate quitline use by adult patients scheduled for elective surgery. METHODS: After formative work involving patients and clinicians, a brief intervention was designed to facilitate telephone quitline use. It was then evaluated in a randomized trial of 300 adults scheduled for elective surgery. A control standard brief stop-smoking intervention served as a comparator, with both interventions delivered by clinicians. The primary outcome was the use rate of a quitline accessed through a dedicated toll-free telephone number, with use defined as completing at least one full counseling session. Secondary outcomes included self-reported abstinence from cigarettes at 30 and 90 days postoperatively. RESULTS: Subject characteristics were similar between the two groups. Records from the designated quitline documented that 29 of 149 subjects (19.5%) in the quitline intervention group and 0 of 151 subjects in the control group completed the first full counseling session (P < 0.0001). There were no significant differences in the self-reported point-prevalent and continuous abstinence rates between groups at either 30 or 90 days postoperatively, although rates tended to be higher in the quitline intervention group. CONCLUSIONS: Clinicians can effectively facilitate quitline use by surgical patients. Further work is necessary to evaluate the efficacy of this approach in terms of long-term abstinence from cigarette smoking.

A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain.

AIMS: Because smoking cessation rates might be improved by combining drugs and by reducing post-cessation weight gain, we tested the smoking cessation efficacy, safety and effect on body weight of adding the nicotine patch to rimonabant, a cannabanoid type-1 receptor antagonist that reduces body weight. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Fifteen US research centers. PARTICIPANTS: A total of 755 smokers (> OR = 15 cigarettes/day). Intervention Rimonabant (20 mg daily) was given open-label for 9 weeks. The 735 participants completing week 1 were randomized at day 8 (target quit day) to add a nicotine patch (n = 369) or placebo patch (n = 366) for 10 weeks (21 mg daily for 8 weeks plus a 2-week taper). Participants received weekly smoking counseling and were followed for 24 weeks. MEASUREMENTS: Biochemically validated 4-week continuous abstinence at end-of-treatment (weeks 6-9; primary end-point); 7-day point prevalence abstinence at weeks 9 and 24; sustained abstinence (weeks 6-24); change in body weight; and adverse events. FINDINGS: Rimonabant plus nicotine patch was superior to rimonabant plus placebo in validated continuous abstinence at weeks 6-9 (39.0% versus 21.3%; odds ratio 2.36, 95% confidence interval: 1.71-2.37; P < 0.01) and in all other efficacy measures. Mean end-of-treatment weight gain among quitters did not differ between groups (0.04 kg for combination versus 0.49 kg for rimonabant only, P = 0.15) and was similar in weight-concerned smokers. Serious adverse event rates did not differ between groups. Depression- and anxiety-related adverse events occurred in 32 (4.2%) and 44 (5.8%) subjects, respectively; eight (1.1%) and nine (1.2%) subjects stopped the drug due to depression and anxiety, respectively. CONCLUSIONS: Adding a nicotine patch to rimonabant was well tolerated and increased smoking cessation rates over rimonabant alone. There was little post-cessation weight gain in either group, even among weight-concerned smokers, during drug treatment.

Gender differences among smokers receiving interventions for tobacco dependence in a medical setting.

OBJECTIVE: The purpose of this study was to assess differences between women and men receiving treatment for tobacco dependence through a clinical treatment program. METHODS: We conducted a retrospective review of clinical data collected on 2139 ambulatory and 1259 hospitalized smokers receiving individualized tobacco dependence treatment from Jan 1, 2004 to Dec 31, 2005 through the Mayo Clinic Nicotine Dependence Center. RESULTS: Overall, female smokers smoked less than males (p<0.001); were less likely to have received treatment for alcoholism (p<0.001); were more likely to have received treatment for past depression (p<0.001); were also less likely to have started smoking prior to 18 years of age (p=0.004 and p=0.008 for ambulatory and hospitalized patients, respectively); were less likely to be married (p<0.001); were less likely to be tobacco dependent (hospitalized smokers only p=0.04); and were more likely to have received a prescription for a smoking cessation medication (ambulatory smokers only, p=0.034). After adjustment for baseline characteristics, women and men did not differ in tobacco abstinence outcomes. CONCLUSION: Although many gender differences are present among patients treated in a large ambulatory and hospital based tobacco treatment programs, gender is not associated with failure to achieve smoking abstinence.

Telephone quitlines to help surgical patients quit smoking patient and provider attitudes.

BACKGROUND: The scheduling of elective surgery provides an excellent opportunity for cigarette smoking-cessation interventions. Abstinence from smoking may improve immediate surgical outcomes, and the surgical period represents a teachable moment for modifying smoking behavior. However, a variety of barriers to intervention exist. This qualitative, formative research identified themes to guide the development of a brief intervention used by the providers of surgical services to promote the use of telephone quitlines. METHODS: Structured interviews were conducted in 2007 with 19 cigarette smokers either scheduled for or recently receiving surgery at Mayo Clinic, Rochester MN and ten providers of surgical services (anesthesiologists and surgeons). RESULTS: Prominent patient themes included interest in quitting smoking around the time of surgery, a view of physicians having an important role in their cessation attempts, and a profound lack of knowledge regarding telephone quitline services. Patients were also poorly informed regarding the immediate benefits of quitting to surgical outcomes. Prominent provider themes included a similar ignorance of quitline services and a lack of time to deliver interventions. Although providers expressed interest in referring to quitlines if this could be easily accomplished, they were willing to spend only a limited amount of time learning how to intervene. CONCLUSIONS: Both surgical patients and providers are potentially receptive to a quitline-based smoking-cessation intervention in the peri-operative period, but significant barriers exist.

Predictors of smokeless tobacco abstinence.

OBJECTIVES: To investigate predictors of tobacco abstinence among smokeless tobacco (ST) users. METHODS: Logistic regression analyses assessed characteristics associated with tobacco abstinence among ST users receiving bupropion SR. RESULTS: Older age was associated with increased tobacco abstinence in both placebo and bupropion SR groups at end of treatment and one year. Abstinence was lower at one year for subjects with a history of major depression. At end-of-treatment, a 2-way interaction was detected suggesting bupropion SR may be efficacious for subjects with other household tobacco users. CONCLUSIONS: Younger ST users and those with a history of depression are less likely to quit ST use.

Hollywood quits--behind the scenes of a Hollywood-based smoking cessation program.

OBJECTIVES: To develop, implement, and assess the efficacy of a comprehensive, evidence-based smoking cessation program for entertainment industry workers and their families. METHODS: Study participants were recruited from 5 outpatient medical clinics and a worksite setting. Tobacco use data were collected during the initial counseling visit and at 6-month follow-up. Univariate and multivariate regressions were used in analysis. RESULTS: More than 50% of participants (n=470) self-reported 7-day abstinence at follow-up. The majority of participants used combination cessation medications, with more than 50% still using at least 1 medication at 6 months. CONCLUSIONS: This evidence-based smoking cessation program using behavioral counseling and combination pharmacotherapy was successful with entertainment industry workers.

Treating tobacco dependence: review of the best and latest treatment options.

Globally, an estimated 85% of lung cancer in men and 47% of lung cancer in women is attributable to tobacco smoking. Tobacco dependence treatment remains the most cost-effective way to prevent morbidity and mortality from lung cancer. Several effective pharmacotherapies are available to treat tobacco dependence. However, the long-term effectiveness of these treatments has been limited because the majority of smokers who attempt to stop smoking eventually relapse. Approaching the treatment of tobacco use and dependence as a chronic disease and the development of innovative drug therapies offer new hope for the treatment of tobacco-dependent patients. The diagnosis of lung cancer provides a teachable moment to motivate patients to attempt tobacco abstinence on which clinicians should capitalize. We review the currently available pharmacologic approaches to the treatment of tobacco dependence.

Bupropion SR for the treatment of smokeless tobacco use.

BACKGROUND: No pharmacotherapies have been shown to increase long-term (> or = 6 months) tobacco abstinence rates among smokeless tobacco (ST) users. Bupropion SR has demonstrated potential efficacy for ST users in pilot studies. We conducted a multicenter, randomized, double-blind, placebo-controlled, clinical trial to assess the efficacy and safety of bupropion SR for tobacco abstinence among ST users. METHODS: Adult ST users were randomized to bupropion SR titrated to 150 mg twice daily (N=113) or placebo (N=112) for 12 weeks plus behavioral intervention. The primary endpoint was the 7-day point-prevalence tobacco abstinence rate at week 12. Secondary outcomes included prolonged and continuous tobacco abstinence rates, craving and nicotine withdrawal, and weight gain. RESULTS: The 7-day point-prevalence tobacco abstinence rates did not differ between bupropion SR and placebo at the end treatment (53.1% versus 46.4%; odds ratio (OR) 1.3; p=0.301). The 7-day point-prevalence abstinence did not differ at weeks 24 and 52. The prolonged and continuous tobacco abstinence rates did not differ at weeks 12, 24, and 52. A time-by-treatment interaction was observed in craving over time with greater decreases in the bupropion SR group. At 12 weeks, the mean (+/-S.D.) weight change from baseline among abstinent subjects was an increase of 1.7 (+/-2.9)kg for the bupropion SR group compared to 3.2 (+/-2.7)kg for placebo (p=0.005). CONCLUSIONS: Bupropion SR did not significantly increase tobacco abstinence rates among ST users, but it significantly decreased craving and weight gain over the treatment period.

Effect of high-dose nicotine patch therapy on tobacco withdrawal symptoms among smokeless tobacco users.

No pharmacotherapies have been shown to increase long-term (> or = 6-month) abstinence rates among smokeless tobacco (ST) users. Available evidence suggests that underdosing may occur with standard-dose nicotine replacement therapy (NRT) in ST users. We investigated the effect of high-dose nicotine therapy on tobacco withdrawal symptoms among ST users in a randomized, controlled clinical pilot study. A total of 42 ST users using at least 3 cans or pouches per week were randomized to nicotine patch doses of 63, 42, or 21 mg/day or placebo for 8 weeks. Multiple daily assessments of tobacco withdrawal and nicotine toxicity were obtained with an electronic diary. During the first week of nicotine patch therapy, we observed a dose-response relationship such that higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.87, p = .009), less negative affect (chi2 = 3.85, p = .05), and less restlessness (chi2 = 3.90, p = .048). During the second week, higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.77, p = .009). Overall, the frequency of nicotine toxicity symptoms did not differ by dose group. Of specific symptoms, nausea was observed to be more frequent in the 63 mg/day dose group compared with placebo (p = .035). In conclusion, high-dose nicotine patch therapy resulted in a greater reduction of tobacco withdrawal symptoms among ST users using at least 3 cans per week. High-dose nicotine patch therapy is safe and well tolerated in this population of tobacco users.

Nicotine lozenges for the treatment of smokeless tobacco use.

Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. We conducted an open-label, one-arm, phase II clinical trial to evaluate the efficacy of the 4-mg nicotine lozenge for the treatment of withdrawal and craving associated with tobacco abstinence among ST users. Eligible subjects received 4-mg nicotine lozenges for 6 weeks followed by a 6-week taper. Subjects completed daily tobacco withdrawal diaries, and data on lozenge use, adverse events, and lozenge acceptability were collected. Urine anabasine was collected at 3 and 6 months for biochemical confirmation of self-reported tobacco abstinence. Participants were 30 ST users with a mean age of 35.4 years (SD=6.5) using an average of 4.2 cans or pouches (SD=3.2) of ST per week for a mean of 15.1 years (SD=6.5). Among subjects continuously tobacco abstinent for the first 2 weeks, no significant increases in composite withdrawal symptoms were observed, compared with baseline symptoms, whereas craving decreased significantly. Biochemically confirmed 7-day point-prevalence tobacco abstinence was 53% (95% CI=34%-72%) at 12 weeks (end of treatment) and 47% (95% CI=28%-66%) at 6 months. Few adverse events attributable to the nicotine lozenge occurred, and the lozenge was perceived as helpful in assisting subjects quit ST. The use of the 4-mg nicotine lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in ST users. Future phase III clinical trials investigating the efficacy of nicotine lozenges are warranted.

Nicotine percentage replacement among smokeless tobacco users with nicotine patch.

To obtain preliminary evidence on the safety and efficacy of high dose nicotine patch therapy among smokeless tobacco (ST) users who consume > or =3 cans of ST per week, we conducted a randomized, placebo-controlled clinical trial with 42 ST users randomized to nicotine patch doses of 21, 42, and 63 mg/day or placebo. Serum nicotine concentrations were measured during ad libitum ST use and nicotine replacement therapy, and percentages of nicotine replacement were calculated. We observed substantial inter-subject variability in nicotine concentrations with ad lib ST use. The mean percentage replacement of ad lib ST use serum nicotine concentrations approximated 100% with the 42 mg/day patch dose (mean+/-S.D., 98.4%+/-45%). Dosing with the 21 mg/day nicotine patch was associated with mean "under-replacement" (53.2%+/-17.1%), and the 63 mg/day nicotine was associated with mean "over-replacement" (159.2%+/-121.9%). We observed symptoms of nausea consistent with nicotine toxicity in two subjects in the 63 mg/day group while no subjects in the 42 mg/day reported these symptoms. We conclude that the use of 42 mg/day nicotine patch therapy is safe and should be considered as initial therapy in the clinical setting among ST users who use > or =3 cans/week.

Measuring nicotine dependence among smokeless tobacco users.

The objective of this study was to assess the concurrent validity of the FTQ-ST and the DIS-IV diagnosis of nicotine dependence among 68 adult ST users enrolled in a randomized, controlled clinical trial of bupropion SR. FTQ-ST scores were not found to differ between those with and without a current DIS-IV diagnosis of nicotine dependence (7.4+/-2.1 vs. 6.8+/-2.8, P=0.325). For all possible FTQ-ST cutoff scores, the observed agreement between the FTQ-ST and the DIS-IV was not found to be different from that expected due to chance. FTQ-ST total scores were positively correlated with serum cotinine (Spearman's r=0.40, P<0.001), amount of tobacco used (r=0.51 and r=0.41 for average dips/chews per day; average tins/pouches per week, respectively, P<0.001), and a reduced likelihood of abstinence at 3 months (OR=0.76, 95% C.I. 0.61-0.96; P=0.019). Participants meeting DIS-IV criteria had lower cotinine concentrations than those without this diagnosis (411+/-263 ng/ml vs. 493+/-246 ng/ml; P=0.042). Poor concordance was observed between the FTQ-ST and the DIS-IV in the assessment of nicotine dependence in ST users.

A survey of characteristics of smokeless tobacco users in a treatment program.

OBJECTIVE: To determine the characteristics and outcomes of smokeless tobacco (ST) users receiving interventions in an outpatient tobacco-dependence treatment program. METHODS: Survey was mailed with telephone follow-up to ST users treated during a 2-year period. RESULTS: Nicotine replacement therapy and family and social support were the most helpful intervention components in maintaining tobacco abstinence. Continuing ST users face significant barriers to abstinence such as high levels of nicotine dependence, lack of motivation, nicotine withdrawal symptoms, and stress. CONCLUSIONS: Enhancing confidence in their ability to quit, managing stress, prescribing bupropion SR, offering nicotine replacement therapy to relieve withdrawal symptoms, and providing ongoing support may be important for ST users in tobacco- dependence treatment programs.

Anesthesiologists, general surgeons, and tobacco interventions in the perioperative period.

Surgery presents an opportunity for interventions in cigarette smokers that will facilitate abstinence from tobacco. However, little attention has been paid to the role of anesthesiologists and surgeons in addressing tobacco use. To determine the practices and attitudes of these physicians regarding this issue, we sent a postal mail survey to a national random sampling of anesthesiologists and general surgeons engaged in active practice within the United States (1000 in each group). Response rates were 33% and 31% for anesthesiologists and surgeons, respectively. More than 90% of both groups almost always ask their patients about tobacco use, and almost all respondents believed that surgical patients should maintain abstinence after surgery. Most believed that it was their responsibility to advise their patients to quit smoking, but only 30% of anesthesiologists and 58% of surgeons routinely do so. Nonetheless, approximately 70% of both groups would be willing to spend an extra 5 min before surgery to help their patients quit. Barriers to intervention included a lack of training regarding intervention techniques, a perceived lack of effective interventions, and insufficient time to intervene. Intervention opportunities are not exploited consistently in the surgical population; educational efforts directed at physicians in surgical specialties are indicated.

Smokeless tobacco: an emerging addiction.

Smokeless tobacco (ST) use is an important health issue in the United States, and chronic use leads to significant morbidity. ST users are exposed to levels of nicotine comparable with smokers and experience symptoms of nicotine withdrawal when attempting to stop. Clinical treatment of ST users requires an understanding of the unique characteristics of ST. This article reviews ST products, epidemiology, pharmacology, health risks, and treatment approaches.

Weight concerns among male smokers.

Many smokers perceive that smoking controls their body weight and that stopping smoking leads to weight gain. This study examined characteristics associated with weight concerns in 72 male smokers enrolled in a controlled trial for smoking cessation. Motivation to quit smoking was found to be significantly lower in those with weight concerns (P < .001). Further investigation is needed to enable the tailoring of interventions for weight-concerned male smokers.

Residential treatment for smokeless tobacco use: a case series.

We developed and implemented a novel 8-day residential treatment program for smokeless tobacco (ST) use. A multidisciplinary team delivered behavioral treatment, nicotine patches were adjusted to achieve 100% replacement of baseline peak serum nicotine concentrations, and bupropion sustained-release was prescribed. Mean participant age (+/- SD) was 47.4 +/- 18.2 years. Mean nicotine patch dose at program end was 43.2 mg/day +/- 13.9 (range 14 to 66 mg/d). Median percent replacement by serum nicotine concentrations was 86.6% (IQR: 75-113.8%). At 1 year, the biochemically-confirmed (urine anabasine <2.0 ng/mL) self-reported 7-day point prevalence tobacco abstinence rate was 58% (14/24). A residential treatment program for ST users may be effective. More research is needed to replicate our findings and determine if comparable abstinence rates can be achieved with outpatient ST treatment programs using similar behavioral and pharmacotherapies.

Teaching motivational interviewing to first-year medical students to improve counseling skills in health behavior change.

OBJECTIVE: To examine the effectiveness of motivational interviewing training on improving medical students' knowledge of and confidence in their ability to counsel patients regarding health behavior change. SUBJECTS AND METHODS: In the spring of 2002, 42 first-year medical students participated in a counseling course on health behavior change. Three small groups focused on learning and practicing motivational interviewing techniques using brief lectures, interactive class activities, student role-plays, and simulated patients. Students completed an identical precourse and postcourse questionnaire that measured their confidence and knowledge regarding counseling skills in health behavior change. RESULTS: The medical students reported improved confidence in their understanding of motivational interviewing after participation in the course (very confident, 77%) compared with before the course (very confident, 2%). Each of the 8 confidence items were compared before and after the course using a signed rank test. All comparisons indicated a significant improvement (P < .001) in confidence. Regarding knowledge-based questions, students showed significant improvement; 31% of students answered all the questions correctly before the course, and 56% answered all the questions correctly after the course (P = .004). CONCLUSION: These results show that teaching motivational interviewing techniques to first-year medical students can enhance student confidence in and knowledge of providing counseling to patients regarding health behavior change.