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.
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 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.