Bupropion XL and SR have similar effectiveness and adverse event profiles when used to treat smoking among patients at a comprehensive cancer center.

BACKGROUND AND OBJECTIVES: Bupropion extended-release (XL; once-daily dosing) has equal efficacy with the sustained-release (SR) formulation (twice-daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open-label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking. METHODS: Cancer patients (N = 648) were prescribed bupropion XL (n = 454) or SR (n = 194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7-day point prevalence abstinence at end-of-treatment (EOT; 3 months postmedication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications. RESULTS: There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent-to-treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR. CONCLUSIONS: Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking. SCIENTIFIC SIGNIFICANCE: In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.

Effect of Sustained Smoking Cessation Counseling and Provision of Medication vs Shorter-term Counseling and Medication Advice on Smoking Abstinence in Patients Recently Diagnosed With Cancer: A Randomized Clinical Trial.

Importance: Persistent smoking may cause adverse outcomes among patients with cancer. Many cancer centers have not fully implemented evidence-based tobacco treatment into routine care. Objective: To determine the effectiveness of sustained telephone counseling and medication (intensive treatment) compared with shorter-term telephone counseling and medication advice (standard treatment) to assist patients recently diagnosed with cancer to quit smoking. Design, Setting, and Participants: This unblinded randomized clinical trial was conducted at Massachusetts General Hospital/Dana-Farber/Harvard Cancer Center and Memorial Sloan Kettering Cancer Center. Adults who had smoked 1 cigarette or more within 30 days, spoke English or Spanish, and had recently diagnosed breast, gastrointestinal, genitourinary, gynecological, head and neck, lung, lymphoma, or melanoma cancers were eligible. Enrollment occurred between November 2013 and July 2017; assessments were completed by the end of February 2018. Interventions: Participants randomized to the intensive treatment (n = 153) and the standard treatment (n = 150) received 4 weekly telephone counseling sessions and medication advice. The intensive treatment group also received 4 biweekly and 3 monthly telephone counseling sessions and choice of Food and Drug Administration-approved cessation medication (nicotine replacement therapy, bupropion, or varenicline). Main Outcome and Measures: The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence at 6-month follow-up. Secondary outcomes were treatment utilization rates. Results: Among 303 patients who were randomized (mean age, 58.3 years; 170 women [56.1%]), 221 (78.1%) completed the trial. Six-month biochemically confirmed quit rates were 34.5% (n = 51 in the intensive treatment group) vs 21.5% (n = 29 in the standard treatment group) (difference, 13.0% [95% CI, 3.0%-23.3%]; odds ratio, 1.92 [95% CI, 1.13-3.27]; P < .02). The median number of counseling sessions completed was 8 (interquartile range, 4-11) in the intensive treatment group. A total of 97 intensive treatment participants (77.0%) vs 68 standard treatment participants (59.1%) reported cessation medication use (difference, 17.9% [95% CI, 6.3%-29.5%]; odds ratio, 2.31 [95% CI, 1.32-4.04]; P = .003). The most common adverse events in the intensive treatment and standard treatment groups, respectively, were nausea (n = 13 and n = 6), rash (n = 4 and n = 1), hiccups (n = 4 and n = 1), mouth irritation (n = 4 and n = 0), difficulty sleeping (n = 3 and n = 2), and vivid dreams (n = 3 and n = 2). Conclusions and Relevance: Among smokers recently diagnosed with cancer in 2 National Cancer Institute-designated Comprehensive Cancer Centers, sustained counseling and provision of free cessation medication compared with 4-week counseling and medication advice resulted in higher 6-month biochemically confirmed quit rates. However, the generalizability of the study findings is uncertain and requires further research. Trial Registration: ClinicalTrials.gov Identifier: NCT01871506.

Second-generation antidepressants for preventing seasonal affective disorder in adults.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Antidepressant Prescription and Risk of Lung Cancer: A Nationwide Case-Control Study.

INTRODUCTION: In recent decades, concern about safety of antidepressants has been raised but the risk between antidepressants and lung cancer has not yet been established. METHODS: A case-control study was conducted by using a nationwide database in Taiwan. The case groups were new onset lung cancer diagnosis during 1999-2008 and age- and gender-matched controls were selected among those without any cancer. The cumulative exposure dose before the lung cancer diagnosis was added and risks were calculated according to the levels of defined daily dose and classes of antidepressants. RESULTS: A total of 39,001 individuals with lung cancer and 189,906 individuals without lung cancer between 1999 and 2008 were included in the analysis. Antidepressants, of any class, were not associated with elevated risks for lung cancer with the exception of bupropion at high exposure levels (odds ratio=4.81, 95% confidence interval=1.39-16.71). DISCUSSION: Antidepressant prescription was not associated with elevation of lung cancer incidence using a nationally representative sample. The elevated risk for lung cancer with bupropion at high doses may be a bias by indication and warrant longitudinal investigation.

[Reversible cerebral vasoconstriction syndrome following smoking cessation and treatment with bupropion]. / Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

TITLE: Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model.

AIM: Depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. In the present study we used ovariectomized (OVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones. METHODS: OVX animals were treated with bupropion (30, 60 mg·kg(-1)·d(-1)) for six weeks. Bone turnover biomarkers (urinary DPD/Cr ratio, serum BALP, OC, TRAcP 5b, CTX and sRANKL levels) and inflammatory cytokines (TNF-α, IL-1ß and IL-6) were determined using ELISA. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine the femoral bone mineral concentrations. The cortical and trabecular morphometric parameters of femoral bones were determined using micro-CT scan and histopathology. RESULTS: In OVX rats, the levels of bone turnover biomarkers and inflammatory cytokines were significantly elevated and femoral bone Ca(2+) and PO4(3-) concentrations were significantly reduced. Moreover, cortical and trabecular morphometric parameters and histopathology of femoral bones were severely altered by ovariectomy. Bupropion dose-dependently inhibited the increases in bone turnover biomarkers and inflammatory cytokines. OVX rats treated with the high dose of bupropion showed normal mineral concentrations in femoral bones. The altered morphometric parameters and histopathology of femoral bones were markedly attenuated by the treatment. CONCLUSION: Bupropion exerts osteo-protective action in OVX rats through suppressing osteoclastogenesis-inducing factors and inflammation, which stabilize the osteoclasts and decrease bone matrix degradation or resorption.

Promoting smoking cessation.

Cigarette smoking causes significant morbidity and mortality in the United States. Physicians can use the five A's framework (ask, advise, assess, assist, arrange) to promote smoking cessation. All patients should be asked about tobacco use and assessed for motivation to quit at every clinical encounter. Physicians should strongly advise patients to quit smoking, and use motivational interviewing techniques for patients who are not yet willing to stop smoking. Clinical contacts with unmotivated patients should emphasize the rewards and relevance of quitting, as well as the risks of smoking and anticipated barriers to abstinence. These messages should be repeated at every opportunity. Appropriate patients should be offered pharmacologic assistance in quitting, such as nicotine replacement therapies, bupropion, and varenicline. Use of pharmacologic support during smoking cessation can double the rate of successful abstinence. Using more than one type of nicotine replacement therapy ("patch plus" method) and combining these therapies with bupropion provide additional benefit. However, special populations pose unique challenges in pharmacotherapy for smoking cessation. Nicotine replacement therapies increase the risk of birth defects and should not be used during pregnancy. They are usually safe in patients with cardiovascular conditions, except for those with unstable angina or within two weeks of a coronary event. Varenicline may increase the risk of coronary events. Nicotine replacement therapies are safe for use in adolescents; however, they are less effective than in adults. Physicians also should arrange to have repeated contact with smokers around their quit date to reinforce cessation messages.

Agitated delirium associated with therapeutic doses of sustained-release bupropion.

CASE DESCRIPTION: We report a case of a patient initiated on therapeutic doses of sustained-release bupropion for the management of major depressive disorder who subsequently developed acute agitated delirium that required ICU level care. This patient's history was significant for alcohol and cannabis abuse but he was currently detoxified and beyond the withdrawal period. Throughout the course of treatment, all maintenance medications, including bupropion, were discontinued and the patient required escalating doses of benzodiazepines and typical antipsychotics to resolve symptoms. The patient's delirium subsided after approximately 5 days. CONCLUSION: Dopamine is thought to play a role in the pathophysiology of delirium and given the mechanism of action of this drug and the presence of delirium risk factors in our patient, we are faced with a likely causative factor of this acute delirious episode.

Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.

Major depressive disorder in the elderly is associated with increased morbidity and reduced quality of life. This 10 week, placebo-controlled study investigated the efficacy and tolerability of extended-release bupropion (150-300 mg once daily) in depressed patients aged 65 years or older. The statistical assumptions necessary for the validity of the protocol-specified analysis of covariance were not met for the analysis of the primary outcome variable (Montgomery-Asberg Depression Rating Scale total score at Week 10, last observation carried forward). Alternative statistical methods used for the analysis of this variable demonstrated statistical significance. Statistically significant improvements were observed on the majority of secondary end points when compared with placebo, including the health outcome measures for motivation and energy, and life satisfaction and contentment. Adverse events were generally mild to moderate and similar between treatment groups. This study demonstrated that the extended-release bupropion is an effective, well-tolerated treatment for major depression in the elderly.

Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring.

Nicotine occurs in tobacco smoke. It is a habit-forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased AMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother's milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals exposed to nicotine via the placenta and mother's milk, and thus during phases of lung development characterized by rapid cell division, is likely due to 'programming' induced by nicotine. Since varenicline, a partial nicotine agonist, has basically the same structure as nicotine, and also binds to acetylcholine receptors in competition with nicotine (but with largely the same effect), it is not advisable to use nicotine or varenicline during gestation and lactation. Furthermore, the use of individual vitamin supplements is also not advisable because of the negative impact on the program that controls maintenance of lung structural and functional integrity and aging. A more appropriate smoking cessation program will also include a mixture of antioxidant nutrients such as in tomato juice.

A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence.

The present study investigated the efficacy of nefazodone and bupropion-sustained release for treating cannabis dependence. A double-blind, placebo-controlled, piggy back design was employed to assess if nefazodone and bupropion-sustained release increased the probability of abstinence from cannabis and reduced the severity of cannabis dependence and cannabis withdrawal symptoms during a 13-week outpatient treatment program. One-hundred and six participants (Mean = 32 years; females n = 25) were randomized to one of three medication conditions (nefazodone, bupropion-sustained release, or placebo) and participated in a weekly, individually based coping skills therapy program. Results indicated an increased probability of achieving abstinence over the course of treatment and a decrease in the severity of cannabis dependence and the withdrawal symptom of irritability. There were no significant effects demonstrated for nefazodone and bupropion-sustained release on cannabis use or cannabis withdrawal symptoms. The results indicate nefazodone and bupropion-sustained release may have limited efficacy in treating cannabis dependence.

A randomized trial of short psychotherapy versus sustained-release bupropion for smoking cessation.

AIMS: To compare the efficacy and safety of a novel psychological intervention for smoking cessation called psychodynamic model (PDM) training to an active control condition of sustained-release bupropion. DESIGN: Randomized controlled clinical trial with allocation concealment. SETTING: Private psychiatric practice. PARTICIPANTS: Seven hundred and seventy-nine adult smokers recruited by advertising. INTERVENTIONS: PDM training (n = 366 participants) consisted of a very brief (1.5 days) psychoeducation and a supervised training in autosuggestion techniques (guided imageries) aimed at enhancing self-management, decidedness, assertiveness, security and competence in relationships, natural functions of organs and awareness of bodily functions. Bupropion SR (n = 413) was increased to 150 mg twice daily over 1 week and given over a 8-week period. MEASUREMENTS: Twelve-month continuous abstinence confirmed by exhaled carbon monoxide (CO) of 9 parts per million (p.p.m.) or less at all interviews conducted at 3, 6 and 12 months. FINDINGS: Intention-to-treat analysis revealed Russell standard 12-month continuous abstinence rates of 39.1% in the psychotherapy group versus 12.3% in the bupropion SR group (P < 0.001) with a relative benefit (RB) of 3.16 (2.38-4.26). Completer analysis revealed 12-month continuous abstinence rates of 39.9% in the psychotherapy group versus 22.5% in the bupropion group [P < 0.001; RB 1.78 (1.35-2.34)]. Of note, bupropion abstinence rates were comparable to previous medications/placebo-only comparisons in geographically different samples. CONCLUSIONS: The 1.5-day psychotherapy exceeded bupropion's efficacy, presenting an alternative to pharmacological smoking cessation aids, especially for smokers who reject drugs to treat their substance dependence, at a similar cost (Euro 350) as the bupropion treatment (Euro 355).

Initial uptake and evidence of safe prescribing practice with Buproprion (Zyban).

PURPOSE: To study the effect of safety concerns and the introduction of freely available nicotine replacement therapy (NRT) on the prescribing of Buproprion within the General Medical Services (GMS) scheme in Ireland. METHODS: Using the state-supported GMS prescription database in Ireland, we identified 8166 patients who were prescribed Buproprion and 18,450 patients who were prescribed NRT over a 12-month-period. RESULTS: A decline in the prescribing of Buproprion was noted which coincided with concerns regarding the safety of the drug but which preceded the introduction of NRT to the GMS. Furthermore, patients who were prescribed Buproprion were less likely to be co-prescribed potentially interacting drugs (odds ratio (OR): 0.48, 95% confidence intervals (CI): 0.42, 0.54) or drugs known to reduce seizure threshold (OR: 0.63, 95% CI: 0.6, 0.67) indicating good prescribing practice. Patients aged 65 years or more were less likely to be prescribed any form of smoking cessation therapy compared with those aged <65 years (OR: 0.23, 95% CI: 0.22-0.24) indicating that such therapy was targeted at those most likely to benefit. CONCLUSIONS: We provide evidence that prescribers exercised caution in the prescription of Buproprion and were likely to have been influenced both by the safety concerns and the introduction of freely available NRT to the GMS population.

Benefits and risks of pharmacological smoking cessation therapies in chronic obstructive pulmonary disease.

Smoking cessation is the most effective way to reduce the risk of developing chronic obstructive pulmonary disease (COPD) or to reduce its progression. However, little is known about the efficacy and safety of different pharmacological smoking cessation therapies used for the treatment of patients with COPD who smoke. The aim of this review was to evaluate the benefits and risks of pharmacological smoking cessation therapies in COPD. We conducted an extensive computer-aided literature search which resulted in the identification of four papers that met the inclusion criteria and contributed to this review. In two studies the efficacy of nicotine polacrilex (nicotine gum) was assessed. In one study, which did not have a control group, the efficacy of nicotine nasal spray was evaluated. The fourth study, a placebo-controlled trial, evaluated the efficacy of bupropion sustained release. The results of these studies indicated that nicotine gum, nicotine nasal spray and bupropion have a good safety profile and seem to increase abstinence rates in smokers with COPD. The incidence and nature of specific adverse effects occurring in patients with COPD seem to be comparable with the adverse effects reported by healthy smokers. However, the efficacy seems to depend on the follow-up period used to define success (i.e. abstinence rates decline with longer follow-up), as well as the intensity and duration of the concomitant psychosocial intervention. This review indicates that for a continuation of the effect of pharmacological smoking cessation therapies, the combination of pharmacotherapy (to reduce craving and withdrawal) and a relapse-prevention programme, in which attention is focused on the behavioural aspects of smoking and smoking cessation, seems to increase abstinence, especially when the psychosocial intervention is prolonged for a longer period. Also, the characteristics of the smokers who are motivated to quit must be taken into account in order to increase the number of successful attempts to quit smoking and prevent relapses. We therefore recommend using a holistic approach in which the possible coexistence of multiple problems (which are known to affect the success of smoking cessation strategies) is integrated.