Review of bupropion for smoking cessation

The advent of bupropion hydrochloride sustained release (Zyban) has heralded a major change in the options available for smoking cessation pharmacotherapy. Bupropion is a selective re-uptake inhibitor of dopamine and noradrenalin which prevents or reduces cravings and other features of nicotine withdrawal. Bupropion is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation. For this review a total of 221 papers were reviewed plus poster presentations. This review examines in detail original clinical trials on efficacy, categorised according to whether they were acute treatment trials in healthy smokers; studies in specific populations such as people with depression, chronic obstructive pulmonary disease (COPD) or cardiovascular disease; or relapse prevention studies. Overall, these studies in varying populations comprising over four thousand subjects, showed bupropion consistently produces a positive effect on smoking cessation outcomes. The evidence highlights the major public health role that bupropion has in smoking cessation. The methodological issues of published clinical trials reporting one year outcomes were examined in detail including: completeness of follow-up; loss to follow-up; intention to treat analysis; blindness of assessment; and validation of smoking status. The review discusses contraindications, adverse effects, dose and overdose, addictive potential, and the role of bupropion in reducing cessation-related weight gain. Bupropion combined with or compared to other pharmacotherapies (nicotine patch; nortriptyline) is considered. Impressive evidence exists for the use of bupropion in smoking cessation among difficult patients who are hard-core smokers such as those with cardiovascular disease, chronic obstructive pulmonary disease (COPD) and depression. Bupropion reduces withdrawal symptoms as well as weight gain and is effective for smoking cessation for people with and without a history of depression or alcoholism. Serious side effects of bupropion use are rare. The major safety issue with bupropion is risk of seizures (estimated at approximately 0.1%) and it should not be prescribed to patients with a current seizure disorder or any history of seizures. In clinical trials of bupropion for smoking cessation no seizures were reported. Allergic reactions occur at a rate of approximately 3% and minor adverse effects are common including dry mouth and insomnia. [Richmond R, Zwar N. Review of bupropion for smoking cessation. Drug Alcohol Rev 2003;22:203 - 220]     

Pharmaceutical strategies for smoking cessation during pregnancy

ABSTRACT

Introduction

Tobacco use is the most preventable cause of death worldwide, with over 7 million deaths per year. Smoking during pregnancy causes harm to the mother, fetus, and can result in problems for the infant from childhood into adulthood. Practitioners should ask all expectant mothers about tobacco use. For expectant mothers who smoke or recently quit, practitioners should advice to quit and provide psychosocial interventions. Rates of smoking during pregnancy differ between geographical locations, with estimates of 10.8% in the UK and 7.2% in the US. Practitioners should provide expectant mothers unable to quit smoking with information about the risks and benefits of pharmacotherapy and use a patient-centered approach to determine the use. Although there is no definitive evidence on birth outcomes, nicotine replacement therapy and bupropion are adequate pharmacotherapies to help those unable to quit.     

Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation

Sustained-release bupropion (bupropion SR) is a unique, non-nicotine smoking cessation aid that is hypothesised to act upon neurological pathways involved in nicotine dependence. Pharmacokinetic and metabolism studies reveal that bupropion SR is metabolised by multiple pathways with no single pathway predominating. When one pathway is inhibited, others are available to compensate. Therefore, only a few clinically relevant drug-drug interactions involving bupropion SR have been observed, although the potential for interactions exists, as with any extensively metabolised drug. Population pharmacokinetic/pharmacodynamic analyses of data from patients receiving daily oral doses of 100mg, 150mg, or 300mg reveal that the anti-smoking efficacy of bupropion SR is directly related to dose. The incidences of dry mouth and insomnia were directly related to bupropion plasma concentrations while the incidence of anxiety was inversely proportional to bupropion plasma concentrations. To maximise efficacy (with an acceptable safety profile), the optimal daily dose for the majority of patients is 300mg.     

Pharmacotherapies to enhance smoking cessation during pregnancy

Smoking during pregnancy is a significant public health concern. Maternal smoking increases the risk of spontaneous abortion, low birth weight, premature delivery, sudden infant death syndrome and learning and behavioral problems in the offspring. Unfortunately, the majority of pregnant women do not quit smoking during pregnancy. Although pharmacotherapy may improve smoking cessation rates in pregnancy, very few studies exist that have studied the safety and efficacy of medications to treat pregnant smokers. This article reviews the available safety and efficacy data for the use in pregnancy of the five first-line therapies and two second-line therapies that are recommended for smoking cessation in non-pregnant smokers. Other promising nicotine replacement therapies are also reviewed. Ultimately, the choice whether to use pharmacotherapy for smoking cessation should be made jointly by the pregnant smoker and her health care provider. This article reviews factors that may be considered when prescribing pharmacotherapy to pregnant smokers (i.e. the role of behavioral counseling, identification of appropriate patients, potential advantages and disadvantages of each of the pharmacotherapies, proposed monitoring strategies, dose and duration and goals of treatment). More research regarding the safety and efficacy of pharmacotherapy during pregnancy is needed to define the risk/benefit profile of each medication for use in smoking cessation in pregnant women. [Oncken CA, Kranzler HR. Pharmacotherapies to enhance smoking cessation during pregnancy. Drug Alcohol Rev 2003;22:191 - 202]     

Chest pain during use of bupropion as an aid in smoking cessation

AIMS: To investigate the cause of chest pain during the use of bupropion as an aid to stop smoking. METHODS: The Netherlands Pharmacovigilance Centre received 22 reports of chest pain, associated with the use of bupropion as an aid to smoking cessation. Additional information about long-term follow up was collected to analyze whether these complaints herald manifest cardiac disease. RESULTS: All but one patient recovered after withdrawal of bupropion. Seven patients were additionally investigated and in six of them, a cardiac cause could be excluded. During long-term follow-up, no coronary heart diseases were diagnosed. CONCLUSIONS: These reports indicate that chest pain seems to be associated with the use of bupropion, but its origin remains unclear.     

Mediating mechanisms for the impact of bupropion in smoking cessation treatment

Several studies have documented the effectiveness of bupropion for smoking cessation, yet little is known about the mechanisms by which it facilitates abstinence. In this placebo-controlled randomized trial. We examined whether bupropion's effects on cessation were mediated by changes in withdrawal and/or negative or positive affect (PA). Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo, plus behavioral counseling. Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models. Cotinine-verified 7-day point prevalence cessation rates at the end of treatment (8-weeks post quit date) were 48% for bupropion and 29% for placebo (P=0.001). There were significant treatment effects on withdrawal and negative affect (NA); however, only change in NA predicted cessation. In a path model, change in NA was a significant mediator of bupropion's effects on cessation. However, the proportion of variance accounted for by this mediator was small, suggesting that other unmeasured factors play an important role. Laboratory-based paradigms may be useful to identify other mediators of bupropion's effects, thereby pointing to mechanisms of effect that can be bolstered in future treatment studies.     

Use of sustained-release bupropion in specific patient populations for smoking cessation

Smoking cessation trials of sustained-release bupropion (bupropion SR) were initially conducted in a general population of smokers who were motivated to quit smoking. Bupropion SR has also been found to be a useful treatment of tobacco dependence in various special populations of smokers who often experience difficulty in overcoming tobacco addiction. Point-prevalence quit rates at 6 months were higher in those treated with bupropion SR than in those receiving placebo in studies on smokers with chronic obstructive pulmonary disease (23% vs 16%) and in those with cardiovascular disease (34% vs 12%). Abstinence from smoking after treatment with bupropion SR was not affected by a history of major depression or alcoholism. Women treated with bupropion SR were just as likely as men to abstain from smoking. Approximately one-third of a study population who were initially unwilling or unable to quit smoking were able to reduce their smoking by 50% or more during therapy with bupropion SR; 14% of these went on to achieve abstinence. Bupropion SR was well tolerated in these trials; importantly, it had no clinically significant effect on mean blood pressure in smokers, including those with hypertension, and attenuated the weight gain associated with smoking cessation, particularly in women.     

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia

The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.     

Clinical efficacy of bupropion in the management of smoking cessation

Nicotine addiction is a chronic relapsing condition that can be difficult to treat. Until recently, pharmacological options for the treatment of tobacco dependence were primarily limited to nicotine replacement therapy (NRT). Sustained-release bupropion (bupropion SR) is the first non-nicotine pharmacological treatment approved for smoking cessation. Bupropion SR is recommended for first-line pharmacotherapy alongside NRT in the updated US Clinical Practice Guidelines and the UK Health Education Authority Guidelines. The UK National Institute of Clinical Excellence recommends NRT and bupropion SR for smokers who have expressed a desire to quit smoking. This review presents evidence that bupropion SR is an effective first-line therapy for smoking cessation in a wide range of patient populations. It is associated with significantly higher smoking cessation rates compared with placebo in patients with or without a history of prior bupropion SR or NRT use, and its effect is independent of gender. Bupropion SR treatment is effective in the prevention of relapse to smoking in those patients who have successfully quit, and re-treatment is effective in smokers who recommence smoking after a previous course of bupropion SR. Bupropion SR treatment relieves the symptoms of craving and nicotine withdrawal, and attenuates the weight gain that often occurs after smoking cessation. Data collected from motivational support programmes and employer-based studies provide strong evidence of the effectiveness of bupropion SR as an aid to smoking cessation in 'real life' situations, and confirm the efficacy seen in clinical trials.     

Predictors of 12-month outcome in smokers who received bupropion sustained-release for smoking cessation

AIM: To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release (SR) 150 or 300 mg/day combined with behavioural counselling. DESIGN, SETTING, PARTICIPANTS: Smokers were recruited from a large healthcare system and then randomized to receive either bupropion SR 150 mg/day (n = 763) or 300 mg/day (n = 761) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach. MEASUREMENTS AND FINDINGS: A comprehensive set of relevant individual pretreatment and treatment characteristics was included in the analysis. Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact. Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months. Seven subgroups were identified among those receiving bupropion SR 150 mg/day (proportion of nonsmokers at 12 months ranged from 13.7% to 43.5%) and eight subgroups among those receiving bupropion SR 300 mg/day (proportion of nonsmokers at 12 months ranged from 9.6% to 51.7%). In the 150-mg/day group, those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer. In the 300 mg/day group, those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level. Across all subgroups, cost per 12-month quitter ranged from a low of USD302 to a high of USD2,502. CONCLUSIONS: These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR, with substantial cost consequences. Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt.     

Tolerability and safety of sustained-release bupropion in the management of smoking cessation

Sustained-release bupropion (bupropion SR) was first launched in the US in 1997 as an aid to smoking cessation and has since been launched in many other countries. Adverse events associated with the use of bupropion SR at the recommended dosage of 150mg twice daily in clinical trials most commonly included insomnia, headache, dry mouth, nausea and anxiety; insomnia and anxiety are also recognised as symptoms of nicotine withdrawal. Only insomnia and dry mouth occurred significantly more frequently with bupropion SR than with placebo. Relative to placebo, no significant changes in mean values for heart rate, blood pressure or routine laboratory parameters have been reported in smokers using bupropion SR alone in clinical trials. When bupropion SR was compared with a nicotine transdermal patch in a clinical trial, insomnia predominated in the bupropion SR group, while dream abnormalities were more common in smokers using the nicotine patch. Bupropion SR and the nicotine transdermal patch in combination can be used safely (with appropriate monitoring) as an aid to smoking cessation. Infrequent but clinically important adverse reactions to bupropion SR include seizures and hypersensitivity reactions: in controlled clinical trials of bupropion SR (300 mg/day), where smokers were carefully screened for risk factors for seizure, the incidence of both seizures and severe hypersensitivity reactions was approximately 0.1% for each event. In order to avoid a risk of seizure of greater than 0.1%, smokers should be screened for predisposing risk factors and adhere to the manufacturer's dosage recommendations (maximum daily dose of 300mg). Thus, bupropion SR is generally well tolerated, as seen by the low discontinuation rate due to an adverse event in clinical trials (6 to 12%). The most common adverse events (insomnia and dry mouth) are generally transient and often resolve quickly without therapeutic intervention; they can be managed if necessary by a reduction in bupropion dose.     

Cost effectiveness of varenicline versus bupropion and unaided cessation for smoking cessation in a cohort of Finnish adult smokers

Abstract

Objective:

To assess the cost effectiveness of varenicline compared with bupropion or unaided cessation for smoking cessation in Finnish adult smokers.     

Amfebutamone/bupropion for smoking cessation: new preparation. Nicotine replacement therapy is safer

(1) For smokers who want to quit and who qualify for pharmacological support, the various forms of nicotine replacement therapy available in France yield a one-year cessation rate of about 14-18%, compared to about 10% with placebo. (2) Amfebutamone (also known as bupropion) is structurally related to an amphetamine psychostimulant. (3) The clinical file mainly contains data from a dose-finding study, two placebo-controlled trials, and a trial comparing amfebutamone + transdermal nicotine with amfebutamone + transdermal placebo. (4) It has not yet been shown that the approved dose regimen of 300 mg/day is more effective than 150 mg/day, or that the treatment period of 7-9 weeks is optimal. (5) Compared to placebo, the one-year cessation rate was only about 13% higher (absolute value) in one trial, much less in the dose-finding study (3%), and not determined in the other two trials. The trial comparing amfebutamone with nicotine suffers from too many methodological weaknesses to show any difference in the efficacy of the two drugs. There has been no specific assessment of amfebutamone in patients with coronary heart disease. (6) There is no basis for combining amfebutamone with nicotine replacement therapy, as there is no evidence of higher efficacy. Furthermore, cardiovascular risk may be increased. (7) Amfebutamone can have serious adverse effects: the estimated risk is approximately 0.1% for convulsions and 3% for potentially severe hypersensitivity reactions. The adverse effects seem to be similar to those of appetite-suppressant amphetamines, including insomnia, weight loss and hypertension. The possible risk of heart valve disease has not been ruled out, because echocardiographic follow-up studies have not been done. (8) Potential adverse effects and drug interactions should contraindicate the use of amfebutamone by patients with a history of cardiovascular, neurological or psychiatric disorders. (9) In practice, when someone needs drug support to quit smoking, nicotine replacement therapy should be tried first.     

A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder

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.     

Spontaneous smoking cessation during pregnancy among ethnic minority women: a preliminary investigation

This study examined the postpartum relapse rates and characteristics of pregnant women who stopped smoking without professional intervention. Baseline characteristics of women who spontaneously quit were compared to women who continued to smoke. Women who spontaneously quit were also randomized to a psychotherapy relapse prevention treatment, or to usual care. The sample was ethnically diverse, containing 141 low-income women who were predominantly Hispanic, 23% (n=33) of whom spontaneously quit smoking. The variables that significantly differentiated between "spontaneous quitters" and ongoing smokers were entered into a regression analysis, which revealed that higher self-confidence, smoking fewer cigarettes per day, and younger age accounted for 25% of the variance in spontaneous cessation. Adding the psychotherapy intervention conferred no additional protection against relapse in this subgroup of spontaneous quitters. The six-month abstinence rate of 36% is similar to that found in Caucasian and higher-income populations. These results extend research with pregnant smokers to a new population and may have implications for healthcare providers and policy makers.