A comparison of smoking cessation treatments for persons with schizophrenia and other serious mental illnesses. A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. A placebo controlled trial of bupropion for smoking cessation in schizophrenia. A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia. Comparison of two intensities of tobacco dependence counseling in schizophrenia and schizoaffective disorder. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Effects of sustained-release bupropion among persons interested in reducing but not quitting smoking. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. Acute feasibility and safety of a smoking reduction strategy for smokers with schizophrenia. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Long-term effectiveness of two Dutch work site smoking cessation programs. Smoking cessation or reduction with nicotine replacement therapy: a placebo-controlled double blind trial with nicotine gum and inhaler. A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Efficacy of bupropion and predictors of successful outcome in a sample of French smokers: a randomized placebo-controlled trial. Treatment for cigarette smoking among depressed mental health outpatients: a randomized clinical trial. Bupropion for smokers hospitalized with acute cardiovascular disease. Does stage-based smoking cessation advice in pregnancy result in long-term quitters? 18-month postpartum follow-up of a randomized controlled trial. A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation: preliminary results.
Adults with any DSM-IV diagnosed mental illness smoke nearly half of the cigarettes consumed in the U.S. (Lasser et al. 2000). This study compared two smoking cessation interventions for persons with schizophrenia or other serious mental illness because national data suggests that: (1) they smoke at two to three times the rate of the general population; (2) cessation interventions for this population are understudied; (3) most cessation studies exclude persons with serious mental illness; and (4) cessation results in public health care savings and disposable income savings for clients. This study included a large number of persons with serious mental illness (N=181) who were randomly assigned to one of three groups: contingent reinforcement (CR), CR plus nicotine patch (21 mg, CR+NRT) for 16 weeks, and a minimal intervention, self-quit control group. These participants were followed for 36 weeks. CR was accomplished with escalating financial compensation for achieving and maintaining abstinence as verified by expired carbon monoxide (CO). Quit rates, as measured by expired CO, were higher and discordant with saliva cotinine quit rates. Cotinine showed lower quit rates and small differences between intervention and control participants at weeks 20 and 36. There was, however, evidence of reduced smoking and importantly, no evidence of psychiatric exacerbation. Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia.
                A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26).
                Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia.
                Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia. The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation. The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt. Schizophrenic patients have high rates of cigarette smoking compared with the general population. We compared sustained-release (SR) bupropion with placebo for smoking cessation in patients with schizophrenic disorders. We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion.
                Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were randomized to bupropion SR (BUP, 300 mg/day) or placebo (PLA). Outcomes included treatment retention, smoking abstinence rates, expired breath carbon monoxide (CO) levels, psychotic symptoms, and medication side effects.
                Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [BUP, 8/16 (50.0%), PLA, 2/16 (12.5%); chi(2) = 5.24, df = 1, p <.05], and reduced CO levels during the trial [Medication x Time interaction; Z = 3.09, p <.01]. Positive schizophrenia symptoms were not altered by BUP, but negative symptoms were significantly reduced. Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP. Major side effects were dry mouth, gastrointestinal symptoms, headache, and insomnia.
                Our results suggest that 1) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers; 2) BUP is well-tolerated and safe for use in these patients; and 3) atypical antipsychotics may enhance smoking cessation outcomes with BUP. The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention. Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions.
                This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia.
                Using a double-blind, placebo-controlled, between-groups design, 57 non-treatment-seeking participants were randomized to receive 300 mg/day bupropion or placebo. One week later, participants were randomized to a contingency management (CM) intervention in which reductions in urinary cotinine levels were reinforced, or a non-contingent reinforcement (NR) condition in which session attendance was reinforced, regardless of cotinine level. Over the 22-day study period, participants visited the laboratory approximately three times per week to provide urine samples for analysis of cotinine levels, to give breath samples for analysis of carbon monoxide (CO) levels, and to report number of cigarettes smoked per day, nicotine withdrawal symptoms, cigarette craving, and psychiatric symptoms.
                Cotinine and CO levels significantly decreased during the study period in participants randomized to the CM condition, but not the NR condition. Bupropion did not reduce cotinine levels or increase the efficacy of CM. Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups.
                The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia. Compared to the general population, smokers with schizophrenia (SCZ) have reduced success in quitting smoking with usual approaches. This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia (TANS) or Medication Management (MM)-for smokers who were motivated to quit. Individual counseling sessions were provided by mental health clinicians in mental health settings, along with nicotine patch. The two treatments varied in intensity and frequency of sessions. Eighty-seven subjects were randomized and attended at least one treatment session. Twenty-one percent (n = 18) of participants had continuous abstinence at 12 weeks after the target quit date, which was not significantly different between conditions (15.6% TANS vs. 26.2% MM, chi(2) = 1.50, p = .221). Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide. Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence.
                Copyright 2010 Elsevier Inc. All rights reserved. Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.
                A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.
                During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.
                Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation. To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit.
                Current smokers were assigned randomly to receive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduction phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued.
                Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the placebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent continuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), although the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P <0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25).
                Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these benefits were modest and not sustained after bupropion was discontinued. The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder.
                Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans.
                A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects.
                Outpatient clinics.
                A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline.
                Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention.
                A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose).
                Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits. The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.
                To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.
                Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.
                Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.
                Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.
                For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).
                Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.
                clinicaltrials.gov Identifier: NCT00141206. The authors examined whether smoking while wearing a transdermal nicotine patch over 32 h was well-tolerated and led to smoking suppression in heavy smokers with schizophrenia. In a crossover design, 10 male veteran smokers with schizophrenia were admitted for two brief inpatient stays to smoke while wearing a transdermal nicotine or placebo patch. Carbon monoxide in expired air, self-reported cigarettes per day, nicotine plasma levels, and psychiatric ratings were measured. Nicotine levels increased during active patch treatment, without evidence of nicotine toxicity. Psychiatric symptoms, carbon monoxide and cigarettes per day did not change, although eight subjects had a decrease in expired carbon monoxide on the active patch. Dyskinesias showed a small, but significant, increase during smoking plus active patch. The heaviest smokers (identified by placebo phase nicotine plasma level or CO level above group median; n = 5) had a statistically significant decrease in expired carbon monoxide of at least 20%. Smoking while wearing the nicotine patch over 32 h was well tolerated. Significant decreases in carbon monoxide smoking indices were seen for the heaviest smokers. These findings suggest further investigation of a smoking reduction intervention in this population. Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.
                To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).
                A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.
                Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.
                Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).
                During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).
                Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.
                clinicaltrials.gov Identifier: NCT00143364. Schizophrenic patients have high rates of cigarette smoking. The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications.
                Forty-five subjects were randomly assigned to 1) the group therapy program of the American Lung Association (N=17) or 2) a specialized group therapy program for smokers with schizophrenia (N=28) that emphasized motivational enhancement, relapse prevention, social skills training, and psychoeducation. All subjects participated in 10 weeks of treatment with the nicotine transdermal patch (21 mg/day) and 10 weekly group therapy sessions and continued to receive their prestudy atypical (N=18) or typical (N=27) antipsychotic medications. Outcome variables included treatment retention, rate of smoking abstinence, and expired-breath carbon monoxide level.
                Smoking abstinence rates did not differ in the two group therapy programs. However, atypical antipsychotic agents, in combination with the nicotine transdermal patch, significantly enhanced the rate of smoking cessation (55.6% in the atypical agent group versus 22.2% in the typical group), which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels. Risperidone and olanzapine were associated with the highest quit rates.
                The results suggest that 1) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia, 2) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation, and 3) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia. Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use.
                To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons.
                A randomized, double-blind, placebo-controlled clinical trial.
                Two urban research sites.
                One thousand five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications.
                Participants were randomized to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. In addition, all participants received 6 individual counseling sessions.
                Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date (postquit), end of treatment (8 weeks postquit), and 6 months postquit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse.
                All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (odds ratios, 1.63-2.34). With such protection, only the nicotine patch plus nicotine lozenge (odds ratio, 2.34, P < .001) produced significantly higher abstinence rates at 6-month postquit than did placebo.
                While the nicotine lozenge, bupropion, and bupropion plus lozenge produced effects that were comparable with those reported in previous research, the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation. This article reports on one of the few experimental studies in Europe to examine work site smoking cessation. The study examined whether a comprehensive intervention (self-help manuals, group courses, a mass media campaign, smoking policies, and a second-year program) is more effective than a minimal intervention (self-help manuals only). Eight work sites participated in the study. The effect of treatment on smoking cessation depended on nicotine dependency levels: Heavy smokers had more success with the comprehensive smoking cessation intervention than with the minimal intervention (with respect to both 14-month quit rate and 6-month prolonged abstinence). For heavy smokers, exposure to mass media exhibitions or to group courses had a beneficial effect on prolonged abstinence. Comprehensive programs may be most appropriate in Dutch work sites with large proportions of heavily addicted smokers. Even with effective smoking cessation medications, many smokers are unable to abruptly stop using tobacco. This finding has increased interest in smoking reduction as an interim step towards complete cessation.
                This multi-center, double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers (N = 314) to reduce or quit smoking. It included smokers willing to control their smoking, and participants could set individual goals, to reduce or quit. The study was placebo-controlled, randomized in a ratio of 2:1 (Active:Placebo), and subjects could choose inhaler or gum after randomization. Outcome was short-term (from Week 6 to Month 4) and long-term (from Month 6 to Month 12) abstinence or reduction. Abstinence was defined as not a single cigarette smoked and expired CO readings of <10 ppm. Smoking reduction was defined as a reduction in number of cigarettes per day by 50% or more versus baseline, verified by a lower-than-baseline CO reading at each visit during the same periods.
                Significantly more smokers managed to quit in the Active group than in the Placebo group. Sustained abstinence rates at 4 months were 42/209 (20.1%) subjects in the Active group and 9/105 (8.6%) subjects in the Placebo group (p = 0.009). Sustained abstinence rates at 12 months were 39/209 (18.7%) and 9/105 (8.6%), respectively (p = 0.019). Smoking reduction did not differ between the groups, either at short-term or long-term. Twelve-month reduction results were 17.2% vs. 18.1%, respectively. No serious adverse events were reported.
                In conclusion, treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum resulted in a significantly higher abstinence rate than placebo. In addition a large number of smokers managed to reduce their cigarette consumption by more than 50% compared to baseline. Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.
                In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24.
                Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively).
                Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. Previous published studies assessed the efficacy of bupropion in smoking cessation only in North American populations of smokers. Results of therapeutic drug trials are not always directly applicable in other populations.
                To confirm the efficacy of bupropion in smoking cessation in European smokers.
                A multi-centre, randomized, double-blind placebo-controlled trial.
                Seventy-four smoking cessation out-patient clinics in France.
                The study included 509 smokers motivated to quit smoking. Intervention Subjects were randomized to either slow-release bupropion 150 mg b.i.d. (B) or to placebo (Pl) in a 2 : 1 ratio, treated for 7 weeks, and followed-up for 26 weeks.
                Main outcome measure: 6 months' point prevalence abstinence, determined by self-report and expired air carbon monoxide measurement. Secondary outcome measures: weeks 4-7 and weeks 4-26 continuous abstinence rates, craving, withdrawal symptoms, weight and cigarette consumption in smokers unable to quit. Adverse events were recorded systematically.
                Six months' point prevalence abstinence rates were 31% and 16%[odds ratio = 2.3, confidence interval (CI) 95%: 1.4-3.7] in the B and Pl groups, respectively. Continuous abstinence rates were 41% (B) and 21% (P) with OR = 2.5 (CI 95%: 1.6-3.9) for weeks 4-7, and 25% (B) and 13% (P) with OR = 2.2 (CI 95%: 1.3-3.6) for weeks 4-26, respectively. Craving decreased significantly more with B than with Pl during treatment period, but there was no difference for total withdrawal symptoms score. Abstinent subjects gained significantly less weight at week 7 with B than with Pl. Low level of nicotine dependence, high motivation, absence of smoking-related disease, long duration of previous quit attempts, male gender, low level of current alcohol problems and living as a couple were predictive of successful cessation. With the exception of marital status, no interaction was observed between any of these predictive factors and the efficacy of bupropion. More of those who continued smoking in the B group than the P group reduced their consumption by at least 50%.
                Sustained-release bupropion is efficacious as an aid to smoking cessation in European smokers. No outcome predictors were identified that might indicate that certain subgroups of smokers would benefit more than others from treatment with bupropion. Using a brief contact control, we tested the efficacy of a staged care intervention to reduce cigarette smoking among psychiatric patients in outpatient treatment for depression.
                We conducted a randomized clinical trial that included assessments at baseline and at months 3, 6, 12, and 18. Three hundred twenty-two patients in mental health outpatient treatment who were diagnosed with depression and smoked > or =1 cigarette per day participated. The desire to quit smoking was not a prerequisite for participation. Staged care intervention participants received computerized motivational feedback at baseline and at 3, 6, and 12 months and were offered a 6-session psychological counseling and pharmacological cessation treatment program. Brief contact control participants received a self-help guide and referral list of local smoking-treatment providers.
                As we hypothesized, abstinence rates among staged care intervention participants exceeded those of brief contact control participants at months 12 and 18. Significant differences favoring staged care intervention also were found in occurrence of a quit attempt and stringency of abstinence goal.
                The data suggest that individuals in psychiatric treatment for depression can be aided in quitting smoking through use of staged care interventions and that smoking cessation interventions used in the general population can be implemented in psychiatric outpatient settings. Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown.
                A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year.
                Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P=.08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P=.49) at 1 year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P=.03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69).
                Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease. To evaluate the effect on quitting smoking at 18 months postpartum of smoking cessation interventions based on the Transtheoretical Model (TTM) delivered in pregnancy compared to current standard care. It has been claimed that TTM-based interventions will continue to create quitters after the end of the intervention period.
                Cluster randomized trial.
                Antenatal clinics in general practices in the West Midlands, UK.
                A total of 918 pregnant smokers originally enrolled in the trial, of which 393 women were followed-up at 18 months postpartum.
                One hundred general practices were randomized into the three trial arms. Midwives in these practices delivered three interventions: A (standard care), B (TTM-based self-help manuals) and C (TTM-based self-help manuals plus sessions with an interactive computer program giving individualized smoking cessation advice).
                Self-reported continuous and point prevalence abstinence since pregnancy.
                When combined together, there was a slight and not significant benefit for both TTM arms compared to the control, with an odds ratio (OR) 95% confidence interval (CI) of 1.20 (0.29-4.88) for continuous abstinence. For point prevalence abstinence, the OR (95%CI) was 1.15 (0.66-2.03). Seven of the 54 (13%) women who had quit at the end of pregnancy were still quit 18 months later, and there was no evidence that the TTM-based interventions were superior in preventing relapse.
                The TTM-based interventions may have shown some evidence of a short-term benefit for quitting in pregnancy but no benefit relative to standard care when followed-up in the longer-term. Cognitive behavior therapy (CBT) constitutes the basis of smoking cessation programs. Quitting rates are usually increased by the concomitant use of CBT and pharmacotherapy. There are studies showing the efficacy of bupropion and nortriptyline compared to placebo, but there is just one published comparison between these drugs, unfortunately with low power to detect significant differences. This study was designed to compare the efficacy of bupropion, nortriptyline and placebo in a group of smokers who also received intensive counseling therapy. We conducted a double blind, double-dummy, placebo-controlled trial for smoking cessation that lasted 9 weeks. Patients were randomized to receive nortriptyline 75 mg/day (52 subjects), bupropion 300 mg/day (53 subjects) or placebo (51 subjects). All smokers also received the same intensive cognitive behavior therapy. The target day for quitting smoking was usually day 10. Intensive counseling was provided at baseline, weekly during treatment, and at 10, 13, 16, 20 and 26 weeks. Abstinence was defined as continuous when the subject was not smoking since the target-quitting day (self-report) and had an expired carbon monoxide concentration of 10 ppm or less.
                The sustained abstinence rates at 6 months were 21.6% in the placebo group, 30.8% in the nortriptyline group (p = 0.40), and 41.5% in the bupropion group (p = 0.05). The odds ratio was not statistically different for smokers using nortriptyline or bupropion (OR 1.60; 95% CI 0.66-3.86; p = 0.35). The most common adverse events were dry mouth and drowsiness in the nortriptyline group and dry mouth and insomnia in the bupropion group.
                Treatment with CBT + bupropion resulted in a better 6-month rate of smoking cessation compared to CBT+nortriptyline or CBT + placebo. Abstinence rate in the nortriptyline group was not statistically different from patients in the bupropion or placebo group.
Bupropion increases smoking abstinence rates in smokers with schizophrenia, without jeopardizing their mental state. Varenicline may also improve smoking cessation rates in schizophrenia, but its possible psychiatric adverse effects cannot be ruled out. CR may help this group of patients to quit and reduce smoking in the short term. We failed to find convincing evidence that other interventions have a beneficial effect on smoking in schizophrenia.