A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation: preliminary results. Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease. Psychological intervention and antidepressant treatment in smoking cessation. 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. Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial. A randomized trial of smoking cessation. Medication versus motivation. A comparison of sustained-release bupropion and placebo for smoking cessation. Bupropion and cognitive-behavioral treatment for depression in smoking cessation. A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse. A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial. A placebo controlled trial of bupropion for smoking cessation in schizophrenia. A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Bupropion and cognitive behavioral therapy for weight-concerned women smokers. Effectiveness of pharmacotherapy and behavioral interventions for smoking cessation in actual clinical practice. Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Bupropion for smoking cessation: a randomized trial. Stopping smoking: a prospective, randomized, double-blind study comparing nortriptyline to placebo. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees. The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial. Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy. Bupropion and nicotine patch as smoking cessation aids in alcoholics. Smoking cessation in primary care - a randomized controlled trial of bupropione, nicotine replacements, CBT and a minimal intervention. A randomized trial of nortriptyline for smoking cessation. Efficacy of bupropion and predictors of successful outcome in a sample of French smokers: a randomized placebo-controlled trial. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder. Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention. Bupropion and cognitive-behavioral therapy for smoking cessation in women. Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia. Extended treatment with bupropion SR for cigarette smoking cessation. Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. 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. Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial. Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression. Efficacy of bupropion alone and in combination with nicotine gum. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. Nicotine patch and paroxetine for smoking cessation. Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment. Sustained-release bupropion for hospital-based smoking cessation: a randomized trial. Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study. Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia. Bupropion for smoking cessation in patients with acute coronary syndrome. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Extended nortriptyline and psychological treatment for cigarette smoking. Bupropion SR vs placebo for smoking cessation in health care professionals. A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot study. Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers. A randomized trial of sertraline as a cessation aid for smokers with a history of major depression. A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers. Bupropion for smokers hospitalized with acute cardiovascular disease.
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. The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge.
                In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date.
                The use of bupropion SR and nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, -1.7% to 22.2%] for nortriptyline). In patients with COPD, bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, -0.8% to 26.4%] for nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found.
                Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative. Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking. It is not known whether psychological intervention increases the efficacy of these antidepressants. This study compared both drugs with placebo. It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention.
                This was a 2 (medical management vs psychological intervention) x 3 (bupropion vs nortriptyline vs placebo) randomized trial. Participants were 220 cigarette smokers. Outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 36, and 52.
                Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone. With the use of point-prevalence abstinence, both nortriptyline and bupropion were more efficacious than placebo. On rates of 1-year continuous abstinence, the 2 drugs did not differ from each other or from placebo. Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence.
                Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers. Similarly, psychological intervention produces better abstinence rates than simple medical management. Both drugs, and psychological intervention, have limited efficacy in producing sustained abstinence. The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone. 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. To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation.
                Pragmatic randomised controlled trial.
                National Health Service stop smoking service clinics.
                901 people trying to stop smoking.
                Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated.
                Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke.
                72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ.
                Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone. Trial registration Current Controlled Trials ISRCTN57852484. A prospective randomized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation.
                Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep University between September 2002 and July 2003. Of these, only 131 patients fulfilled the trial criteria. We randomized the patients into nicotine patch (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24 weeks. Questionnaires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation. Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria.
                Success rates were 26% for nicotine patch group, 26% for bupropion and 16% for control group at the end of the 24th week (p=0.56). Beck depression inventory scores did not differ significantly between the groups, however none of the cases with scores greater than 13 succeeded regardless of the group. Mean body weight at baseline and change at 6 months did not differ significantly between the groups. Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group (p=0.008).
                The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation, and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects. Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.
                At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.
                A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year. This study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment (CBTD) and of bupropion, both singularly and in combination, on smoking cessation in adult smokers. As an extension of our previous work, we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors. Participants were 524 smokers (47.5% female, M (age) = 44.27 years) who were randomized to one of four 12-week treatments: (a) standard, cognitive-behavioral smoking cessation treatment (ST) plus bupropion (BUP), (b) ST plus placebo (PLAC), (c) standard cessation treatment combined with cognitive-behavioral treatment for depression (CBTD) plus BUP, and (d) CBTD plus PLAC. Follow-up assessments were conducted 2, 6, and 12 months after treatment, and self-reported abstinence was verified biochemically. Consistent with previous studies, bupropion, in comparison with placebo, resulted in better smoking outcomes in both intensive group treatments. Adding CBTD to standard intensive group treatment did not result in improved smoking cessation outcomes. In addition, neither CBTD nor bupropion, either alone or in combination, was differentially effective for smokers with single-past-episode major depressive disorder (MDD), recurrent MDD, or elevated depressive symptoms. However, findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample. An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials. To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse.
                A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU).
                Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits.
                Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide <or= 8 parts per million.
                TTR was longer with extended active treatments compared to placebo (median days to relapse: bupropion + placebo = 136, nicotine + placebo = 98, bupropion + nicotine = 90, double placebo = 71). Hazard ratios (HR) for relapse were statistically significant for bupropion + placebo versus double placebo during MT (HR = 0.59, 95% CI = 0.37-0.92) and to the end of NTFU (HR = 0.66, 95% CI = 0.42-0.96). However, bupropion's advantage dissipated upon stopping the drug. Gum use was low, preventing a valid assessment; but analysis restricted to gum users suggested a weak effect of extended nicotine gum.
                Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse; the optimum duration of bupropion treatment was unclear. Further research is needed to ascertain the merits of extended use of nicotine gum, other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved. 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. Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD.
                In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat.
                All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events.
                Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD. 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. Smoking cessation rates with current therapy are suboptimal. Tricyclic antidepressants improve cessation rates. We hypothesized that addition of nortriptyline hydrochloride to transdermal nicotine would enhance cessation rates.
                We conducted a randomized, double-blind, placebo-controlled trial at a Department of Veterans Affairs medical center. Subjects were aged 18 to 65 years, smoked 10 or more cigarettes per day, and did not have current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg 14 days before quit day, titrated to 75 mg/d as tolerated, and continued for 12 weeks after quit day. Transdermal nicotine (21 mg/d) was started on quit day and continued for 8 weeks. The behavioral intervention consisted of 12 brief, individual visits. Withdrawal symptoms were measured by means of a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide level of 9 ppm or less, and a 6-month urine cotinine level less than 50 ng/mL (284 nmol/L).
                A total of 158 patients were randomized (79 to nortriptyline and 79 to placebo). There was no significant reduction in withdrawal symptoms. The cessation rates at 6 months were 23% (18/79) and 10% (8/79), respectively (absolute difference, 13%; 95% confidence interval, 1.3%-24.5%; P = .052). Nortriptyline caused frequent side effects, including dry mouth (38%) and sedation (20%).
                Nortriptyline combined with transdermal nicotine resulted in an increased cessation rate with little effect on withdrawal symptoms. This combination may represent an option for smokers in whom standard therapy has failed. 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.
                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.
                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. 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. We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers.
                In a randomized, double-blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated.
                Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.
                Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns. Trial Registration clinicaltrials.gov Identifier: NCT00006170. This study evaluated the effectiveness of behavioral interventions (brief counseling, nonspecific psychological support in groups - NSGS and cognitive behavioral group therapy - CBGT) in combination with bupropion SR for smoking cessation in the field, through a smoking cessation clinic.
                Two-hundred-and-five smokers were enrolled in a 19-week course during 2007/ 2008, and were randomly assigned to: bupropion SR combined with brief counseling (group A), bupropion SR combined with NSGS (group B), bupropion SR combined with CBGT (group C), or CBGT as the only approach (group D).
                Continuous abstinence rates at the end of therapy were 53.2% for group A, 62.9% for group B, 50.0% for group C, and 22.2% (p < 0.05) for group D. Sustained abstinence rates in 12 months were 29.6%, 28.1%, 34.3% and 19.4% (p > 0.05), respectively.
                Bupropion SR is an effective aid for smoking cessation in clinical practice. NSGT increased the chances for success at the end of therapy when combined with bupropion SR, while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy. It is suggested that smoking cessation interventions in real-life healthcare settings should be implemented through comprehensive programs using pharmacotherapy where applicable, combined with NSGT, and integrated by specialized healthcare professionals. A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence.
                This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date.
                Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men.
                Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline. The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings.
                To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting.
                Open-label randomized trial, with 1 year of follow-up.
                A large health system (Group Health Cooperative) based in Seattle.
                Adult smokers (N = 1524) interested in quitting smoking.
                Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity).
                The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR.
                At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001).
                In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions. 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. Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy.
                A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates.
                During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36).
                In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates. The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation. This study evaluates the efficacy of nortriptyline in an antismoking program.
                A possible randomized double-blind study that included 144 patients who were randomized to receive nortriptyline, 75 mg/d (68 patients), or placebo (76 patients), during 6 consecutive weeks. All patients attended behavioral group orientation for 5 weeks. The rate of success, complications, adherence to the regime, and factors of pretreatment prognosis were evaluated (multivariate analysis).
                The groups were balanced in relation to the characteristics of the patients on entering the study. Patients receiving nortriptyline showed significantly higher cessation rate (55.9%) compared to the group receiving placebo (23.3%; p < 0.001). In a univariate analysis on prognosis factors influencing the rate of cessation in our study, the Fagerström test results (p = 0.005) and nortriptyline (p < 0.001) were identified. Logistic regression showed that a Fagerström test score of < 7 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.47 to 6.7; p = 0.003) and nortriptyline use (OR, 4.1; 95% CI, 2 to 8.3; p < 0.001) were independent factors impacting the rate of success for smoking cessation. No significant complications were observed in the nortriptyline group.
                This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers, as compared to the placebo group, without any significant side effects. Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking and received behavioral counseling. Continuous smoking abstinence during weeks 4-7 was the primary endpoint, and long-term smoking abstinence was among the secondary endpoints. Of the original participants, 212 completed the 6-month trial. Continuous smoking abstinence at week 7 was achieved by 43% in the bupropion group and 18% in the placebo group, p<.001. After 26 weeks, 18% and 7%, respectively, were continuously abstinent, p=.008. Side-effects were frequent but simple and reversible in both groups, and generally consistent with the findings of previous studies. Dizziness, insomnia, and pruritus appeared more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark. Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking.
                A randomized, double-blind, placebo-controlled trial.
                A smoker's cessation clinic.
                One hundred volunteers smoking 10 cigarettes/day or more.
                Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months.
                Continuous abstinence rates recorded at various time points up to 12 months from the quit date.
                The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action.
                We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers. Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation. This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes. Smoking cessation has been shown to be effective in randomized controlled trials. It is unclear though, whether interventions also work in routine primary care.
                In 167 primary care settings we conducted a randomized four-armed smoking cessation trial to examine the efficacy of a minimal intervention (MI; n = 81), cognitive-behavioral therapy (CBT; n = 175), bupropion (BUP; n = 108) and nicotine replacements (NRT; n = 103). Overall, 467 current smokers were enrolled. Abstinence rates at the end of treatment (12 weeks) were 32.8% for MI patients, 34.8% for CBT, 35.3% for NRT, and 46.5% for BUP patients (ITT, intention to treat) (no differential effects). Retention rates were highest in the BUP group (59.3%) and lowest in the NRT group (50.5%). Completer findings were: MI, 56.4%; CBT, 64%; BUP, 79.3%; NRT, 69.2% (LOCF, lost to follow-up). No serious adverse events occurred during or after the medication phase. At 12-month follow-up continuous abstinence rates were: BUP, 29.0%; CBT, 20.9%; NRT, 29.6%; MI, 29.6%.
                Our findings suggest that established smoking cessation treatments are effective when applied by non-specialist primary care physicians. Our data supports a structured, multimodal treatment structure as core ingredient of successful smoking cessation in primary care.
                Copyright © 2011 John Wiley & Sons, Ltd. Smoking cessation rates with current therapy are suboptimal. One class of drugs that may improve cessation is the tricyclics.
                To add nortriptyline hydrochloride to a behavioral smoking cessation program to enhance cessation rates and reduce withdrawal symptoms.
                We conducted a randomized, double-blind, placebo-controlled trial at an affiliated Department of Veterans Affairs Medical Center and an Army Medical Center. Subjects were aged 18 through 70 years, smoked 10 or more cigarettes per day, and were without current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/d or to the maximal tolerated dose. The behavioral intervention consisted of 2 group sessions and 12 individual follow-up visits. Withdrawal symptoms were measured using a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide of 9 ppm or less, and a 6-month urine cotinine level of less than 50 ng/mL.
                A total of 214 patients were randomized (108 to nortriptyline and 106 to placebo). There was a significant reduction in several withdrawal symptoms including anxious/tense, anger/irritability, difficulty concentrating, restlessness, and impatience by day 8 after quit day in the nortriptyline group. The cessation rate at 6 months was 15 (14%) of 108 and 3 (3%) of 106, respectively (P = .003; absolute difference, 11%; 95% confidence interval, -18% to -4%). Nortriptyline caused frequent adverse effects, including dry mouth (64%) and dysgeusia (20%).
                We conclude that nortriptyline led to an increased short-term cessation rate compared with placebo. In addition, there were significant, but relatively small, reductions in withdrawal symptoms. Nortriptyline may represent a new therapeutic approach to smoking cessation. 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. 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. This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD. To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention.
                Smokers were randomized to receive a nicotine inhaler, bupropion, or both for 3 months. At 3 months, smoking-abstinent study participants were randomized to their initial medications or placebo. Participants who were smoking at 3 months were randomized to an alternative treatment regimen or placebo. This study was conducted from July 2001 to January 2003.
                A total of 1700 smokers were randomized to treatment (phase 1) for 3 months. Among the 941 study participants eligible for randomization to the phase 2 trial, 837 continued in the study. For the phase 2 trial, 405 smoking-abstinent participants were randomized to relapse prevention for 9 additional months, and 432 smokers were randomized to re-treatment for an additional 3 months. At the end of the initial 3 months of treatment (phase 1), 82 (14%) of 566, 145 (26%) of 567, and 194 (34%) of 567 study participants receiving a nicotine inhaler, bupropion, or both, respectively, were abstinent from smoking. Of the 405 smoking-abstinent participants at the end of 3 months, the bupropion group had more smokers than the placebo group (mean No. of smokers, 1.5 vs 1.1; P < .001), and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group. Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention, but this difference disappeared after the initial 3 months. Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen, the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo (8 [7%] of 111 vs 0 [0%] of 112; P = .003), and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates (6 [6%] of 104 vs 3 [3%] of 105; P = -.50).
                Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates. Continuation of the initial combination therapy does not appear to prevent relapse to smoking. Timing of re-treatment and alternative approaches to relapse prevention should be further examined. Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women. It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered. This study used a two level factorial design to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]). In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments, we examined medication compliance and its role in the efficacy of bupropion. Participants were 154 women, aged at least 30 years and smoking more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-, 9-, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women. In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy. The authors present results of a randomized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that combined relapse prevention training, bupropion SR, and nicotine patch followed by extended treatment (14 weeks) with bupropion SR or matching placebo. Abstinence percentages were relatively high (week 11: 52%; week 25: bupropion, 42%; placebo, 38%; week 52: bupropion, 33%; placebo, 34%), but bupropion SR did not surpass placebo. Gender and baseline craving level were identified as significant, independent moderators of treatment response. Men were more likely to abstain than women (week 11: 59% vs. 43%, p = .001; week 25: 48% vs. 31%, p = .001; week 52: 39% vs. 27%, p = .01). Because most smokers suffer relapse with any current cessation treatment, the comparatively high abstinence percentages achieved in this trial are of interest.
                Copyright 2006 APA To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and
                Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment.
                Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P =.73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P =.12).
                Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy. 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. Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated.
                This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes.
                In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette.
                The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices.
                These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies. Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse.
                To evaluate the efficacy of bupropion to prevent smoking relapse.
                Randomized, placebo-controlled trial.
                784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day.
                The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking.
                Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less.
                The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016).
                In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain. Randomized efficacy clinical trials conducted in research settings may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical settings. Effectiveness trials (eg, in primary care settings) are needed to estimate the benefits of cessation treatments in real-world use.
                A total of 1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics. Patients were randomly assigned to 5 active pharmacotherapies: 3 monotherapies (nicotine patch, nicotine lozenge, and bupropion hydrochloride sustained release [SR]) and 2 combination therapies (patch + lozenge and bupropion SR + lozenge). Patients were referred to a telephone quit line for cessation counseling. Primary outcomes included 7-day point prevalence abstinence at 1 week, 8 weeks, and 6 months after quitting and number of days to relapse.
                Among 7128 eligible smokers (> or =10 cigarettes per day) attending routine primary care appointments, 1346 (18.9%) were enrolled in the study. Six-month abstinence rates for the 5 active pharmacotherapies were the following: bupropion SR, 16.8%; lozenge, 19.9%; patch, 17.7%; patch + lozenge, 26.9%; and bupropion SR + lozenge, 29.9%. Bupropion SR + lozenge was superior to all of the monotherapies (odds ratio, 0.46-0.56); patch + lozenge was superior to patch and bupropion monotherapies (odds ratio, 0.56 and 0.54, respectively).
                One in 5 smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence-based counseling and medication. In this comparative effectiveness study of 5 tobacco dependence treatments, combination pharmacotherapy significantly increased abstinence compared with monotherapies. Provision of free cessation medications plus quit line counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit. Trial Registration clinicaltrials.gov Identifier: NCT00296647. Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression.
                A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment.
                The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation.
                The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted. In this double-blind, placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at 1 week, end of treatment, and 6 months but not at 12 months postquit. After the first week postquit there were no differences in abstinence rates between the AA and AP groups. We found no significant individual difference variables that moderated outcome beyond 1 week postquit. 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. Smokers (N = 224) were randomized to 1 of 3 groups: (a) transdermal system (TNS) + placebo; (b) TNS + paroxetine (20 mg); (c) TNS + paroxetine (40 mg). Assignment to treatment was double-blind. Nicotine patch (TNS) treatment was provided for 8 weeks; paroxetine or placebo was provided for 9 weeks. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 45%, 36%, and 25%; (b) TNS + paroxetine (20 mg): 48%, 33%, and 21%; (c) TNS + paroxetine (40 mg): 57%, 39%, and 27%. The differences were not statistically significant. The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation. A subgroup analysis comparing compliant participants was also conducted. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 46%, 35%, and 24%; (b) TNS + paroxetine (20 mg): 64%, 43%, and 33%; (c) TNS + paroxetine (40 mg): 74%, 51%, and 38%. The differences between paroxetine groups and placebo at Week 4 were statistically significant. Although paroxetine may add value to the current standard of care in excess of potential risk, more conclusive evidence is needed. The authors evaluated the efficacy of fluoxetine hydrochloride (Prozac; Eli Lilly and Company, Indianapolis, IN) as an adjunct to behavioral treatment for smoking cessation. Sixteen sites randomized 989 smokers to 3 dose conditions: 10 weeks of placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of individualized cognitive-behavioral therapy, and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1, 3, and 6 months posttreatment. Analyses assuming missing data counted as smoking observed no treatment difference in outcomes. Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses. Results support a modest, short-term effect of fluoxetine on smoking cessation and consideration of alternative models for handling missing data. Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers.
                We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates.
                At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12).
                The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions. To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD).
                Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study.
                Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19).
                After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations. 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. Smokers hospitalized with acute coronary syndrome (ACS) are at high risk for subsequent ischemic events. Nevertheless, over two-thirds of patients continue to smoke after an acute myocardial infarction. Bupropion hydrochloride has proven efficacy as a smoking cessation aid, but data regarding its safety and efficacy in ACS patients are limited.
                In a double-blind, randomized controlled trial, we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release (SR) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support. Primary efficacy outcome was smoking abstinence at 1 year. Primary safety outcome was clinical events at 1 year.
                A total of 151 patients were enrolled; all but 2 completed follow-up. Abstinence rates at 3 months were 45% and 44% in the bupropion SR and placebo groups, respectively (P = .99); 37% vs 42% (P = .61) at 6 months; and 31% vs 33% (P = .86) at 1 year. On multivariate analysis, an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.22-14.19). Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation (OR, 0.23; 95% CI, 0.07-0.78). Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index, but dizziness was more common compared with placebo (14% vs 1.4%; P = .005).
                In hospitalized patients with ACS who received continuous, intensive nurse counseling about smoking cessation, bupropion did not increase the rates of smoking abstinence. 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. Accepted treatments for cigarette smoking rarely achieve abstinence rates of >35% at 1 year. Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction. Using a chronic disease model of smoking, the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment.
                One hundred sixty smokers of > or =10 cigarettes/day were randomly assigned to one of four treatment conditions in a two-by-two (nortriptyline versus placebo by brief versus extended treatment) design. All subjects received 8 weeks of a transdermal nicotine patch, five group counseling sessions, and active or placebo treatment. Interventions for subjects in brief treatment ended at this point. Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions, with checkup telephone calls midway through each session. Subjects were assessed at baseline and weeks 12, 24, 36, and 52. The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence.
                At week 52, point-prevalence abstinence rates with missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for placebo extended treatment, 18% for active brief treatment, and 50% for active extended treatment. With missing subjects omitted, these rates were 32%, 57%, 21%, and 56%, respectively.
                Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature. To evaluate bupropion SR for smoking cessation in physicians and nurses.
                This double-blind prospective 26-center, 12-country trial randomized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks. The participants were followed for 52 weeks.
                Bupropion SR was superior to placebo (50% vs 40%, P=0.013) on the 4-week primary outcome variable. Due to a high placebo response in this health care population, statistical differences were not maintained after treatment was discontinued.
                Bupropion SR is effective and well tolerated in health care professionals. Relapse prevention measures are needed to attain long-term abstinence. Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies.
                To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study.
                This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes.
                Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%).
                Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated. Few pharmacological therapies have been shown to increase abstinence rates among spit tobacco (ST) users. Bupropion has been shown to be effective in increasing abstinence rates among smokers but has not been studied in ST users. Sixty-eight adult (aged > or = 18 years old) regular users of ST who were motivated to stop using ST were enrolled in a randomized, double-blind, placebo-controlled pilot study of bupropion sustained release (SR) or placebo for 12 weeks. The primary endpoint was 1-week, biochemically confirmed point-prevalence tobacco abstinence rate at the end of treatment (week 12). Nicotine withdrawal symptoms and weight change were assessed. At the end of 12 weeks of therapy, the point-prevalence tobacco abstinence rate was 44% in the bupropion group and 26% in the placebo group (p = 0.064). At 24 weeks following initiation of medication, the point-prevalence abstinence rate was 29% for both groups. After 7 weeks of medication, subjects on bupropion reported significantly less (p< or = 0.034) nicotine withdrawal than placebo. The mean weight change from baseline to end of treatment was +0.7 +/- 1.9 kg for bupropion and +4.4 +/- 2.4 kg for placebo (p = 0.03). The 6-month weight change for continuously abstinent subjects was 3.4 +/- 3.6 kg in the bupropion group and 6.2 +/- 5.0 kg in the placebo group (p = 0.49). Bupropion may increase abstinence rates in ST users and appears to attenuate weight gain during ST abstinence. Larger randomized, controlled trials of bupropion for ST users are needed. Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch plus placebo, 28% and 7%. Despite the lack of a treatment effect, a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time. Similarly, an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking. These findings are encouraging and suggest new avenues for research. For example, treatments of the kind examined in this report, augmented by extended maintenance therapies, may yield higher long-term success rates. Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated.
                The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits.
                Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed.
                Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline. To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers.
                We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity.
                Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group. No difference occurred for withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3).
                In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence. 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.
The antidepressants bupropion and nortriptyline aid long-term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Adverse events with both medications appear to be rarely serious or lead to stopping medication.