Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

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

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

Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment. METHODS: This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study. RESULTS: The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo). CONCLUSION: Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.

Development and validation of the Wisconsin Smoking Withdrawal Scale.

The accurate assessment of nicotine withdrawal is important theoretically and clinically. A 28-item scale, the Wisconsin Smoking Withdrawal Scale, was developed that contains 7 reliable subscales tapping the major symptom elements of the nicotine withdrawal syndrome. Coefficients alpha for the subscales range from .75 to .93. This scale is sensitive to smoking withdrawal, is predictive of smoking cessation outcomes, and yields data that conform to a 7-factor structure. The 7 scales predicted intratreatment smoking, chi2(7, N = 163) = 15.19, p = .034. Moreover, the questionnaire is sufficiently brief so that it can be used in both clinical and research contexts.

Gender differences in smoking cessation.

Gender differences in smoking quit rates are frequently reported and are the subject of much speculation. This study examined the generalizability of gender differences in abstinence across study sites, treatments, and time of relapse, as well as potential mediators and moderators of gender effects. Participants were smokers who participated in 3 randomized clinical trials of the nicotine patch (N = 632). Men had higher cessation rates than women at all follow-ups. The impact of gender on abstinence was unaffected by controlling for study site, treatment, or time of relapse. There was little evidence for mediation or moderation of this relation by any of a host of predictor variables. The magnitude and consistency of the gender differential, coupled with an inability to account for it, highlights a compelling need for additional research specifically aimed at elucidating the relation between gender and abstinence.

The Agency for Health Care Policy and Research smoking cessation clinical practice guideline: basics and beyond.

The 1996 Agency for Health Care Policy and Research's Smoking Cessation Clinical Practice Guideline provides a strong empirical foundation for effective smoking cessation interventions in primary care. Screening all patients for tobacco use status at each clinic visit and providing at least brief cessation advice to all smokers can have a significant system-wide effect. Adding additional treatment components, such as pharmacotherapy, problem solving, and social support, can increase quit rates by twofold or more. Information on effective and ineffective treatment components is provided, along with new information published after the release of the Guideline.

A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.

Response to nicotine dependence treatment in smokers with current and past alcohol problems.

Smoking prevalence among alcoholics is high, and evidence indicates that smokers with a history of alcohol abuse may have more difficulty quitting cigarette smoking. This study is a post hoc analysis comparing the smoking cessation rates of smokers with active or past alcohol problems to the rates in smokers with no history of alcohol problems who were participants in a randomized, controlled trial of smoking cessation therapy. Subjects received either 44 mg/24 hour or 22 mg/24 hour nicotine patch for 4 or 6 weeks, respectively, followed by a tapering schedule to complete 8 weeks of therapy and a randomly assigned behavioral intervention (minimal, brief individual counseling, group therapy). The Self-Administered Alcoholism Screening Test (SAAST) score was used to determine alcohol group assignment (no alcohol problems < 7; active alcohol problems > or = 7 and still drinking; past alcohol problems if not drinking due to a past history of alcohol problems). Among 382 subjects (171 men and 211 women), 281 had no alcohol problems (74%), 53 had past alcohol problems (14%), and 48 had active alcohol problems (13%). Smoking cessation rates assessed at both weeks 4 and 8 were significantly different across groups (p = 0.026 and 0.002 at weeks 4 and 8, respectively) with lower rates in the groups with past and active alcohol problems when compared to the "no problem" group. At week 26, subjects with past alcohol problems were less likely to be abstinent from smoking than no problem group subjects, but this was not statistically significant (odds ratio = 0.49, 95% confidence interval 0.22-->1.08). In the short term, smokers with past or active alcohol problems are less likely to quit smoking compared to those with no alcohol problems when treated with nicotine patch therapy for smoking cessation.

Are higher doses of nicotine replacement more effective for smoking cessation?

This study determined whether higher dose nicotine patches are more efficacious than lower dose patches among heavy smokers. A randomized double-blind study compared 0, 21, 35, and 42 mg/day of a 24-h patch in 1039 smokers (> or = 30 cigarettes/day) at 12 clinical sites in the USA and one in Australia. Daily patches were used for 6 weeks followed by tapering over the next 10 weeks. Weekly group therapy occurred. Biochemically validated self-reported quit rates at 6, 12, 26, and 52 weeks post-cessation were measured. Quit rates were dose-related at all follow-ups (p < 0.01). Continuous, biochemically verified abstinence rates for the 0, 21, 35, and 42 mg doses at the end of treatment (12 weeks) were 16, 24, 30, and 39%. At 6 months, the rates were 13, 20, 20, and 26%. Among the 11 sites with 12 month follow-up (n = 879), the quit rates were 7, 13, 9, and 19%. In post-hoc tests, none of the active doses were significantly different from each other at any follow-up. The rates of dropouts due to adverse events for 0, 21, 35, and 42 mg were 3, 1, 3, and 6% (p = n.s.). Our results are similar to most prior smaller studies; i.e., in heavy smokers higher doses increase quit rates slightly. Longer durations of treatment may be necessary to show greater advantages from higher doses.

New developments in approaches to smoking cessation.

Tobacco use is the leading cause of unnecessary illness and death in the United States consuming billions of dollars in scarce health care resources. In the period under review, several new treatments for tobacco addiction were introduced. New nicotine delivery systems, a nasal spray and an inhaler, reduced craving and withdrawal compared with placebo and improved medium- to long-term cessation rates. Nicotine patches and gum became available without a prescription in the United States, offering the potential for increased use and synergy between public health efforts and commercial advertising. Important new safety data were obtained on the use of nicotine replacement therapies in potentially high risk groups, such as adolescents, pregnant women, and persons with serious cardiovascular disease, indicating that these therapies pose little or no additional risk.

Smoking cessation: principles and practice based upon the AHCPR Guideline, 1996. Agency for Health Care Policy and Research.

Cigarette smoking remains the leading preventable cause of morbidity and premature mortality in the United States. Although the vast majority of smokers come in contact with the health care system on a regular basis, clinical smoking cessation interventions happen infrequently and in a non-systematic manner. In 1996, the Agency for Health Care Policy and Research (AHCPR) "Smoking Cessation Clinical Practice Guideline" provided detailed clinical practice recommendations based on a review of some 3,000 articles in the research literature and dozens of supporting meta-analyses. This article presents a simple four-step model for clinical smoking cessation interventions, including systematic identification of smoking status, brief cessation advice from clinicians, assessment of patient motivation, and detailed assistance for those willing to stop smoking. It also provides the empirical basis for the AHCPR Guideline recommendations.

Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain.

The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).

Varying nicotine patch dose and type of smoking cessation counseling.

OBJECTIVE: To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal, individual, or group counseling to improve smoking cessation rates. DESIGN: An 8-week clinical trial (4 weeks double-blind followed by 4 weeks open label) using random assignment of participants to both dose (22 or 44 mg) and counseling (minimal, individual, or group) conditions. PARTICIPANTS: Daily cigarette smokers (> or = 15 cigarettes per day for at least 1 year) who volunteered to participate in a study of smoking cessation treatment. A total of 504 participants were enrolled at two sites. INTERVENTION: Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction (2 weeks of 22 mg followed by 2 weeks of 11 mg). Counseling consisted of a self-help pamphlet (minimal); a self-help pamphlet, a brief physician motivational message, and three brief (< 15 minutes) follow-up visits with a nurse (individual); or the pamphlet, the motivational message, and eight weekly 1-hour group smoking cessation counseling visits (group). All participants returned weekly to turn in questionnaires and for assessment of their smoking status. MAIN OUTCOME MEASURES: Abstinence from smoking was based on self-report, confirmed by an expired carbon monoxide concentration lower than 10 ppm. Withdrawal severity was assessed by means of an eight-item self-report questionnaire completed daily. RESULTS: Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date. Among those receiving minimal contact, the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose (68% vs 45%; P < .01). Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling (56% vs 67%; P < .05). The 44-mg dose decreased desire to smoke more than the 22-mg dose, but this effect was not related to success in quitting smoking. Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea (28%), vomiting (10%), and erythema with edema at the patch site (30%) than did a 22-mg dose (10%, 2%, and 13%, respectively; P < .01 for each adverse effect). Three serious adverse events occurred during use of the 44-mg patch dose. CONCLUSIONS: There does not appear to be any general, sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment. The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up, and the higher patch dose produced more adverse effects. Higher-dose (44-mg) nicotine replacement does not appear to be indicated for general clinical populations, although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment.

Smoking status as the new vital sign: effect on assessment and intervention in patients who smoke.

OBJECTIVE: To assess the effect of expanding the vital signs to include smoking status. DESIGN: We prospectively conducted exit interviews with patients at a general internal medicine clinic in Madison, Wisconsin, during a 16-month period from 1991 to 1993. METHODS: Patients were surveyed briefly before (N = 870) and after (N = 994) the implementation of a simple institutional change in clinical practice. This change involved training the staff in how to use progress notepaper with a vital sign stamp that included smoking status (current, former, or never) along with the traditional vital signs. Included in the survey were questions about whether the patient smoked, whether the patient was asked that day about smoking status (by a clinician or other staff), and, for smokers, whether they were urged to quit smoking and given specific advice on how to do so. RESULTS: After expansion of the vital signs, patients were much more likely to report inquiries about their smoking status on the day of a clinic visit (an increase from approximately 58% at baseline to 81% at intervention; P < 0.0001). The vital sign intervention was associated with significant increases in the percentage of smokers who reported that their clinician advised them that day to quit smoking (from approximately 49% at baseline to 70% during the intervention; P < 0.01) and in the percentage who reported that their clinician gave them specific advice that day on how to stop smoking (from approximately 24% at baseline to 43% during the intervention; P < 0.01). CONCLUSION: Expanding the vital signs to include smoking status was associated with a dramatic increase in the rate of identifying patients who smoke and of intervening to encourage and assist with smoking cessation. This simple, low-cost intervention may effectively prompt clinicians to inquire about use of tobacco and offer recommendations to smokers.

Tobacco smoking and new developments in public health and clinical interventions.

The public policy environment regarding tobacco use in the United States has experienced a dramatic change during the past year. Along with calls for regulatory review of cigarettes, important new scientific information has become available regarding the health effects of environmental tobacco smoke and the efficacy of nicotine replacement therapy, which is used to support smoking cessation efforts. Specifically, recent studies have suggested that environmental tobacco smoke exposure increases risk for coronary heart disease in nonsmoking adults in addition to causing lung cancer and other respiratory diseases. Children are exposed to environmental tobacco smoke at home and in public, resulting in increased risk of bronchitis, pneumonia, bronchial hyperresponsivity, and sudden infant death syndrome. In a climate of increasing concern about the direct and indirect effects of tobacco smoke, three independent meta-analyses concluded that nicotine replacement therapy increased smoking cessation efficacy two- to threefold. In addition, research is beginning to identify factors associated with successful and unsuccessful cessation attempts using nicotine replacement therapy, resulting in the possibility of individualized treatments and clinical interventions designed for maximum efficacy.

Are clinicians intervening with their patients who smoke? A "real-world" assessment of 45 clinics in the upper Midwest.

OBJECTIVE: To determine the level of intervention provided by primary care physicians to individuals who smoke. SETTING: 45 primary care clinics throughout the upper Midwest. PATIENTS: 6,086 men and women (M:F = 1:2), ages 50 to 68, who sought medical care at any one of the 45 primary care clinics and completed two questionnaires regarding preventive medical services received during the previous 3 years (1990-1993). RESULTS: Of patients who smoke, 92% reported that their clinician had asked about their smoking status. Additionally, 86% reported being informed at their clinic of the dangers of tobacco use. A smaller percentage of individuals (60.1%) reported being explicitly advised on how to quit, and fewer still (27.2%) reported being referred to a stop smoking program. CONCLUSIONS: While most clinicians inquire about their patients' smoking status and recommend they quit, there currently exists a deficiency in the translation of these recommendations into concise, explicit instructions on how to quit. By increasing the frequency of clinicians giving specific advice about how to quit, the overall success rate of the public health campaign against tobacco use will be greatly enhanced.

Smoking outcome expectancies: factor structure, predictive validity, and discriminant validity.

Recent models of addiction posit that drug outcome expectancies are influential determinants of drug use. The current research examines the dimensional structure, predictive validity, and discriminant validity of expectancies for cigarette smoking in a prospective study. There was a good fit between the factor structure of the Smoking Consequences Questionnaire and the observed data. In addition, the internal consistency of each scale was satisfactory. Moreover, there was considerable evidence for the predictive and discriminant validity of expectancies. Expectancies of positive outcomes (positive reinforcement, negative reinforcement, and appetite-weight control) predicted withdrawal severity. Negative reinforcement expectancies and expectancies of negative consequences predicted cessation success. Predictive relations remained significant after controlling for related constructs: negative affect, stress, and dependence measures.

The effectiveness of the nicotine patch for smoking cessation. A meta-analysis.

OBJECTIVE: To estimate the overall efficacy and optimal use of the nicotine patch for treating tobacco dependence. DATA SOURCES: Nicotine patch efficacy studies published through September 1993, identified through MEDLINE, Psychological Abstracts, and Food and Drug Administration new drug applications. STUDY SELECTION: Double-blind, placebo-controlled nicotine patch studies of 4 weeks or longer with random assignment of subjects, biochemical confirmation of abstinence, and subjects not selected on the basis of specific diseases (eg, coronary artery disease). DATA EXTRACTION: Pooled abstinence rates and combined odds ratios (ORs) at end of treatment and 6-month follow-up were examined overall and in terms of patch type (16-hour vs 24-hour), patch treatment duration, dosage reduction (weaning), counseling format (individual vs group), and intensity of adjuvant behavioral counseling. DATA SYNTHESIS: Across 17 studies (n = 5098 patients) meeting inclusion criteria, overall abstinence rates for the active patch were 27% (vs 13% for placebo) at the end of treatment and 22% (vs 9% for placebo) at 6 months. The combined ORs for efficacy of active patch vs placebo patch were 2.6 at the end of treatment and 3.0 at 6 months. The active patch was superior to the placebo patch regardless of patch type (16-hour vs 24-hour), patch treatment duration, weaning, counseling format, or counseling intensity. The 16-hour and 24-hour patches appeared equally efficacious, and extending treatment beyond 8 weeks did not appear to increase efficacy. The pooled abstinence data showed that intensive behavioral counseling had a reliable but modest positive impact on quit rates. CONCLUSIONS: The nicotine patch is an effective aid to quitting smoking across different patch-use strategies. Active patch subjects were more than twice as likely to quit smoking as individuals wearing a placebo patch, and this effect was present at both high and low intensities of counseling. The nicotine patch is an effective smoking cessation aid and has the potential to improve public health significantly.