Lo clásico y lo nuevo en el tratamiento del sobrepeso y la obesidad / The classic and the new in the treatment of overweight and obesity

Así como planteamos en la primera entrega de esta serie de artículos de actualización sobre la obesidad, resulta urgente revisar el abordaje tradicional que la comunidad médica le ofrece a las personas con cuerpos gordos. En este segundo artículo desarrollaremos en profundidad diferentes alternativas terapéuticas para los pacientes que desean bajar de peso:plan alimentario, actividad física, tratamiento farmacológico y cirugía metabólica. (AU)

As we proposed in the first issue of this series of articles, it is urgent to review the traditional approach that the medical community offers to people with fat bodies. This second article will develop different therapeutic alternatives for patients who want to lose weight: eating plans, physical activity, pharmacological treatment, and metabolic surgery. (AU)

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.

Ketamine treatment protects against oxidative damage and the immunological response induced by electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is often recommended for major depressive disorder (MDD) for those who do not respond to the first and second antidepressant trials. A combination of two therapies could improve antidepressant efficacy. Thus, this study aimed to investigate the synergistic effects of ECT combined to antidepressants with a different mechanism of action. METHODS: Rats were treated once a day, for five days with ketamine (5 mg/kg), fluoxetine (1 mg/kg), and bupropion (4 mg/kg) alone or in combination with ECT (1 mA; 100 V). After, oxidative damage and antioxidant capacity were assessed in the prefrontal cortex (PFC) and hippocampus, and pro-inflammatory cytokines levels were evaluated in the serum. RESULTS: ECT alone increased lipid peroxidation in the PFC and hippocampus. In the PFC of rats treated with ECT in combination with fluoxetine and bupropion, and in the hippocampus of rats treated with ECT combined with ketamine and bupropion there was a reduction in the lipid peroxidation. The nitrite/nitrate was increased by ECT alone but reverted by combination with ketamine in the hippocampus. Superoxide dismutase (SOD) was increased by ECT and maintained by fluoxetine and bupropion in the PFC. ECT alone increased interleukin-1ß (IL-1ß) and the administration of ketamine was able to revert this increase showing a neuroprotective effect of this drug when in combination with ECT. CONCLUSION: The treatment with ECT leads to an increase in oxidative damage and alters the immunological system. The combination with ketamine was able to protect against oxidative damage and the immunological response induced by ECT.

Development and Validation of a Model to Predict Neonatal Abstinence Syndrome.

OBJECTIVES: To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS). STUDY DESIGN: We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation. RESULTS: A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30 day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants. CONCLUSIONS: We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30 days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

[The prevalence of strategies for cessation of tobacco use in primary health care: an integrative review]. / Prevalência de estratégias para cessação do uso do tabaco na Atenção Primária à Saúde: uma revisão integrativa.

The habit of tobacco use/smoking, which is a major concern of Primary Health Care (PHC), is a serious public health problem and the main avoidable cause of death in the world. The relevance of actions, whose focus is to facilitate the cessation of this habit, motivates the discussion of studies that have different approaches to tackle this issue by seeking to train PHC professionals accordingly. A search was conducted in the Lilacs, MEDLINE and Web of Science databases for recent scientific publications (2010-2015). The key words were combined with Boolean operators and, after analysis of the articles found, 75 are discussed in this article since they have strategies with a higher prevalence in PHC. The conclusion drawn is that the brief or intense individual approach using the 5A method (Transtheoretical Model) is the most widely adopted, as well as bupropion and nicotine replacement patches. The increasing use of hard technology requires new studies that examine their impact on the treatment of smokers. It was clearly revealed that there is a need for health professionals to be better prepared to address the issue with the users, in addition to a lack of stimulus and proper conditions to work in the PHC team directly reflecting scientific advances in clinical practice.

O hábito de fumar, ou tabagismo, preocupação da Atenção Primária à Saúde (APS), é um grave problema de saúde pública e a principal causa de morte evitável no mundo. A relevância de ações, cujo foco seja facilitar a cessação deste vício, motiva a discussão de estudos que apresentam diferentes abordagens para tal enfrentamento visando contribuir para a formação dos profissionais da APS. Utilizou-se as bases de dados Lilacs, Medline e Web of Science considerando as produções científicas recentes (2010 a 2015). Os descritores foram combinados a operadores boleanos e, após análise dos artigos encontrados, 75 são discutidos nesta revisão por apresentarem estratégias de maior prevalência na APS. Conclui-se que a abordagem individual breve ou intensa a partir do método dos 5A's (Modelo Transteórico) é a mais adotada, assim como os fármacos adesivos de Nicotina e Bupropiona. O uso crescente de tecnologia dura necessita de novos estudos que averiguem os seus impactos no tratamento a tabagistas. Evidenciou-se a necessidade de o profissional de saúde ser mais bem preparado para abordar o tema com os usuários, além de carecer do estímulo e das condições próprias para atuar na equipe de APS refletindo diretamente os avanços científicos em sua prática clínica.

SMOKING CESSATION TREATMENTS: CURRENT PSYCHOLOGICAL AND PHARMACOLOGICAL OPTIONS.

BACKGROUND: Smoking is considered an epidemic, indeed, one of the most important public health problems worldwide. It is also the most significant preventable cause of death, of a high number of premature deaths, and avoidable chronic diseases. It is considered an enormous economic burden for the world. OBJECTIVE: To provide an overview of smoking-cessation treatments, including pharmacological and psychological options, and to gather current scientific evidence available on them. METHODS: Research included reviewing publications from 2007-2018 in four databases using algorithms related to bupropion, varenicline, nicotine replacement therapy, smoking cessation, psychological treatment, motivational interview, cognitive-behavioral therapy and clinical guidelines for smoking treatment. Meta-analyses or systematic reviews and randomized or quasi-randomized trials were selected. We also included clinical guidelines for smoking treatment from Mexico and other countries. RESULTS: After refining the search, 37 articles met the criteria and were included in the review. The results were grouped by type of intervention. CONCLUSIONS: It is necessary to conduct research on combinations of both kinds of treatment with an integral, multidisciplinary vision. Current standard for smoking cessation is a combined psychological and pharmacological treatment.

Prevalência de estratégias para cessação do uso do tabaco na Atenção Primária à Saúde: uma revisão integrativa / The prevalence of strategies for cessation of tobacco use in primary health care: an integrative review

Resumo O hábito de fumar, ou tabagismo, preocupação da Atenção Primária à Saúde (APS), é um grave problema de saúde pública e a principal causa de morte evitável no mundo. A relevância de ações, cujo foco seja facilitar a cessação deste vício, motiva a discussão de estudos que apresentam diferentes abordagens para tal enfrentamento visando contribuir para a formação dos profissionais da APS. Utilizou-se as bases de dados Lilacs, Medline e Web of Science considerando as produções científicas recentes (2010 a 2015). Os descritores foram combinados a operadores boleanos e, após análise dos artigos encontrados, 75 são discutidos nesta revisão por apresentarem estratégias de maior prevalência na APS. Conclui-se que a abordagem individual breve ou intensa a partir do método dos 5A's (Modelo Transteórico) é a mais adotada, assim como os fármacos adesivos de Nicotina e Bupropiona. O uso crescente de tecnologia dura necessita de novos estudos que averiguem os seus impactos no tratamento a tabagistas. Evidenciou-se a necessidade de o profissional de saúde ser mais bem preparado para abordar o tema com os usuários, além de carecer do estímulo e das condições próprias para atuar na equipe de APS refletindo diretamente os avanços científicos em sua prática clínica.

Abstract The habit of tobacco use/smoking, which is a major concern of Primary Health Care (PHC), is a serious public health problem and the main avoidable cause of death in the world. The relevance of actions, whose focus is to facilitate the cessation of this habit, motivates the discussion of studies that have different approaches to tackle this issue by seeking to train PHC professionals accordingly. A search was conducted in the Lilacs, MEDLINE and Web of Science databases for recent scientific publications (2010-2015). The key words were combined with Boolean operators and, after analysis of the articles found, 75 are discussed in this article since they have strategies with a higher prevalence in PHC. The conclusion drawn is that the brief or intense individual approach using the 5A method (Transtheoretical Model) is the most widely adopted, as well as bupropion and nicotine replacement patches. The increasing use of hard technology requires new studies that examine their impact on the treatment of smokers. It was clearly revealed that there is a need for health professionals to be better prepared to address the issue with the users, in addition to a lack of stimulus and proper conditions to work in the PHC team directly reflecting scientific advances in clinical practice.

Smoking cessation treatments: current psychological and pharmacological options

Abstract Background Smoking is considered an epidemic, indeed, one of the most important public health problems worldwide. It is also the most significant preventable cause of death, of a high number of premature deaths, and avoidable chronic diseases. It is considered an enormous economic burden for the world. Objective To provide an overview of smoking-cessation treatments, including pharmacological and psychological options, and to gather current scientific evidence available on them. Methods Research included reviewing publications from 2007-2018 in four databases using algorithms related to bupropion, varenicline, nicotine replacement therapy, smoking cessation, psychological treatment, motivational interview, cognitive-behavioral therapy and clinical guidelines for smoking treatment. Meta-analyses or systematic reviews and randomized or quasi-randomized trials were selected. We also included clinical guidelines for smoking treatment from Mexico and other countries. Results After refining the search, 37 articles met the criteria and were included in the review. The results were grouped by type of intervention. Conclusions It is necessary to conduct research on combinations of both kinds of treatment with an integral, multidisciplinary vision. Current standard for smoking cessation is a combined psychological and pharmacological treatment.

The effect of paroxetine, venlafaxine and bupropion administration alone and combined on spatial and aversive memory performance in rats.

BACKGROUND: The use of antidepressants in combination is common practice following non-response to single antidepressant agents. Nevertheless, the scientific literature lacks preclinical studies regarding the combined administration of antidepressants across multiple behavioral measures including, but not limited to, cognition. Hence, we aimed to determine the effects of paroxetine (PAR), venlafaxine (VEN) and bupropion (BUP) alone or combined (PAR+BUP or VEN+BUP) on spatial and affective memory tasks to advance the knowledge about the combined use of antidepressants in cognition. METHODS: Adult rats received daily injections (15 days) of PAR (20mg/kg, ip), VEN (20mg/kg, ip), BUP (20mg/kg, ip) alone or combined and were submitted to behavioral measures of spatial memory (radial-arm maze - RAM), aversive memory (passive avoidance - PA), open field (OF) and forced swimming (FST) tests. RESULTS: In the RAM, VEN or VEN+BUP impaired learning, while short-term memory (STM) was impaired by PAR, BUP and their combination. VEN+BUP improved STM as compared to BUP. PAR impaired long-term memory (LTM). VEN or BUP alone impaired STM and long-term fear memory, whilst PAR+BUP or VEN+BUP did not induce significant alterations. CONCLUSIONS: The effects of VEN, PAR or BUP alone and in combination on measures of memory are variable and vary as a function of the pharmacodynamics profile of each drug as well as the specific memory paradigm.

Failure to detect the action of antidepressants in the forced swim test in Swiss mice.

OBJECTIVE: The aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice. METHODS: Male Swiss mice (n=6-8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1-30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes. RESULTS: According to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle. CONCLUSION: Data suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

[Clinical Practice Guidelines for Smoking Cessation]. / Guías de Práctica Clínica para el Tratamiento del Tabaquismo, Chile 2017.

Considering that a high proportion of the Chilean general population smokes, the Chilean Society of Respiratory Diseases in collaboration with the Chilean Societies of Cardiology and, Endocrinology and Diabetes, formed an interdisciplinary group, who issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done with the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table. Recommendations For all smokers, the panel recommends using brief counseling ABC on non-intervention, using mobile telephone interventions on non-intervention, using text message on non-intervention, (strong recommendation; moderate certainty in the evidence of the effects). For motivated individuals, with indication for quitting drugs the panel recommends using nicotine replacement therapy on non-intervention, using bupropion on non-intervention, using varenicline on non-intervention. (strong recommendation; moderate certainty in the evidence of the effects). Discussion This clinical practice guide provides recommendations based on the evidence for smoking cessation.

Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release.

INTRODUCTION: Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

Possible addiction transference from cocaine insufflation to oral bupropion in bipolar patient.

OBJECTIVE: Alert for the risk of oral bupropion addiction in patients with cocaine dependence. METHODS: Single-case study. RESULTS: After a period of cocaine and alcohol abstinence, a 42-year-old patient started taking oral bupropion to relieve the symptoms of cocaine craving. He increased the bupropion dose up to 2250 mg/d without seizures. CONCLUSION: This case highlights the possibility of oral bupropion addiction after cocaine dependence. To our knowledge, it is the first case in the literature and emphasizes the risk of bupropion's misuse. Therefore, physicians should carefully examine the patient's profile before prescribing it, as well as follow appropriate measures.

The first 7 days of a quit attempt predicts relapse: validation of a measure for screening medications for nicotine dependence.

OBJECTIVES: There is a critical need for the development of novel treatments for nicotine dependence. Because the majority of smokers who make a quit attempt fail within 7 days, medication screening procedures that focus on this early cessation period may provide an indicator of treatment efficacy. To establish the clinical validity of this paradigm, it is critical to demonstrate the association of early abstinence with longer-term abstinence. We tested the number of days of abstinence during the first week after the target quit date (TQD) as a predictor of point prevalence abstinence in 3 independent pharmacotherapy trials for nicotine dependence. METHODS: This was a secondary data analysis of 3 randomized clinical trials: a placebo-controlled trial of transdermal nicotine (N = 545); an open-label nicotine replacement therapy (patch vs spray) trial (N = 566); and a bupropion placebo-controlled trial (N = 538). In separate logistic regression models, the maximum number of consecutive days of abstinence during the first week after the TQD was used to predict biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT) and 6 months post-TQD. RESULTS: Across the 3 trials, the number of days of abstinence significantly predicted abstinence at EOT and 6 months (odds ratios > 1.4; Ps < 0.0001). Likewise, not having any lapse during the first week predicted abstinence at EOT and 6 months (odds ratios > 4.7; Ps < 0.0001). CONCLUSIONS: The first week of abstinence was highly predictive of EOT and long-term abstinence. Medication screening procedures that focus on this early abstinence period (ie, 6 or 7 days of consecutive abstinence) represent a valid tool for assessing the presence of a signal for medication efficacy.

Bupropion for control of hot flashes in breast cancer survivors: a prospective, double-blind, randomized, crossover, pilot phase II trial.

CONTEXT: Hot flashes (HFs) and sexual dysfunction often affect breast cancer (BC) survivors and compromise their quality of life. Bupropion is an antidepressive medication used for smoking cessation and also has been previously studied for the treatment of sexual dysfunction. OBJECTIVES: We aimed to evaluate bupropion's efficacy in controlling HFs in BC survivors. METHODS: This was a randomized, double-blind, crossover, placebo-controlled pilot study that enrolled 55 BC survivors who reported more than seven HFs per week. Subjects were randomized to receive either bupropion 150mg twice daily for four weeks followed by one week of washout and four more weeks of placebo twice daily or vice versa. The primary end point was average daily HF activity (number of HFs and a score combining number and severity) reported while on bupropion or on placebo. Secondary end points were sexual dysfunction, depression, and quality of life evaluated with the Arizona Sexual Experience Scale, Beck Depression Inventory, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, respectively. RESULTS: Bupropion reduced HFs by 1.26 per day and the HF score by 6.31%, whereas placebo reduced HFs by 2.11 per day (P>0.05) and the HF score by 30.47% (P>0.05). There were no statistically significant differences between bupropion and placebo in the Arizona Sexual Experience Scale, Beck Depression Inventory, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. At the end of the study, 47% of the patients preferred bupropion, whereas 53% preferred placebo. There were no statistically significant differences in side effects between the study groups. CONCLUSION: Compared with placebo, bupropion did not control HFs in this group of BC survivors.

Effectiveness of coadministration of varenicline, bupropion, and serotonin reuptake inhibitors in a smoking cessation program in the real-life setting.

INTRODUCTION: Varenicline has a significant impact on the ability to quit smoking. However, patients may have side effects similar to nicotine withdrawal symptoms. The aim of this study was to evaluate the effectiveness of varenicline in monotherapy or in combined therapy with bupropion and/or serotonin reuptake inhibitors (SRIs) in a specific cardiovascular smoking cessation service. METHODS: It is an outcome research of 427 patients that received varenicline monotherapy or combined pharmacotherapy and were followed for 52 weeks. Patients were oriented to take varenicline until week 12. During each medical visit, the patients were evaluated and in the cases of mood changes after varenicline use, SRIs were prescribed. Bupropion was combined in patients that did not achieve complete tobacco abstinence in 2 or 3 weeks after starting varenicline use or if the patient presented uncomfortable abstinent symptoms. RESULTS: The success (continuous abstinence rate in 52 weeks) in different drug regimens were: varenicline monotherapy (32.1%), varenicline + bupropion (55.0%), varenicline + SRI (50.6%), and varenicline + bupropion + SRI (57.7%). In a multivariate analysis of successful treatment predictors, compared with varenicline monotherapy, patients who used bupropion + SRI adjuvant treatment had an odds ratio (OR) of 5.05 (1.99-12.80) for a successful treatment response after 1-year follow-up, while patients who used bupropion or SRI had OR of 3.21 (1.68-6.14) and 3.58 (1.98-6.48), respectively. CONCLUSIONS: Our results suggest that adjuvant treatment to varenicline therapy may be associated with improved success in smoking cessation, especially in patients with nicotine withdrawal symptoms. These results should be tested in randomized controlled trials.

Bupropion/naltrexone fixed-dose combination for the treatment of obesity.

The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.

Pharmacogenetics of smoking cessation therapy.

Nicotine dependence is a major health problem, with a large amount of smoking-related premature deaths and disabilities. The dependence mechanism of nicotine is especially complex and is under strong genetic influence. Smoking cessation is associated with substantial health benefits. Evidence from animal and human studies suggests that genetic polymorphisms influencing pharmacokinetics and pharmacodynamics of nicotine may have great potential for aiding smoking treatment. There are more than 30 association studies and one genome-wide association study (GWAS) between genetic polymorphisms and smoking cessation following nicotine replacement therapy (NRT) and/or bupropion therapy. However, only a few candidate genes or regions were analyzed more than twice and even these genes require additional investigations in different therapeutic schemes. There are a growing number of new pharmacologic options that have not been pharmacogenetically assessed according to published literature. In addition, molecular genetics studies are needed to assess the functional mechanisms of some putative association results. Taken together, the preliminary findings are promising but raise the need for new studies with adequate sample sizes and adjustment for several potential confounding factors frequently neglected, such as comorbidity and sociodemographic factors. The current state of the art in the field encourages an optimist view that personalized treatment approaches may become possible. However, the current scientific evidence still does not support the use of pharmacogenetic tests in routine smoking cessation therapy.

Acute effects of pharmacotherapies in blood pressure in normotensive moderate smokers.

This study was designed to evaluate the changes in arterial blood pressure (BP) and heart rate (HR) in moderate smokers during smoking abstinence after 7 days of treatment with bupropion alone, transdermal nicotine or bupropion combined with transdermal nicotine. Twenty-four healthy moderate smokers (12 female/12 male; 40+/-7 years) were evaluated randomly on five occasions and their systolic, diastolic, mean arterial blood pressure (MAP) and HR were measured by a Finapres device for 10 h, immediately after smoking interruption. All of the 24 smokers participated on five protocols during 7 days: control group (C) - no drugs; placebo group (PL); bupropion group (BUP) 150-300 mg; transdermal nicotine group (TN) - 21 mg; and BUP+TN-nicotine patch. Concomitantly, the subjects were evaluated by ABPM (ambulatory BP monitoring). All of BP parameters monitored shown significant statistical differences in the BUP, TN and BUP+TN groups compared with the controls (p<0.05), when measured by Finapres. The HR remained unaltered in all of the groups. No significant differences were seen in the BP or HR during the 24-h ABPM. These findings indicate that in moderate smokers, bupropion, transdermal nicotine or bupropion associated with transdermal nicotine caused an elevation in the BP after acute smoking interruption.

Terapias farmacológicas para dejar de fumar: metaanálisis de estudios aleatorizados controlados / Pharmacotherapies for smoking cessation: a meta-analysis of randomised controlled trials

Objetivo. Comparar los efectos del tratamiento de 7 formas farmacológicas aprobadas para dejar de fumar. Materiales y métodos. Fuente y selección de datos: Búsqueda realizada en Enero de 2008 en la base de datos del Centro para Control y Prevención de Enfermedades relacionadas con el tabaco de Estados Unidos, MEDLINE, EMBASE y la Biblioteca Cochrane. Restringido a idioma inglés solamente. Se contemplaron para este trabajo todos los estudios aleatoririzados controlados (EAC) que reportaran medidas bioquímicas de abstinencia a 6 y 12 meses (p.ej., cotinina en orina). _De los 622 trabajos potencialmente relevantes, 69 (32.908 pacientes totales) cumplieron los criterios de inclusión (EAC con placebo, ciegos, medición de abstinencia 6 y/o 12 meses con confirmación bioquímica). Lois datos fueron obtenidos por dos revisores en forma independiente. Los desacuerdos fueron arreglados por consenso o por un tercer revisor. Cuando fue necesario, se contactó a los autores para mayor información. Resultados. Encontraron las siguientes chamces (odds ratio [OR] para abandono del hábito tabáquico, en orden de efectividad decreciente: vareniclina (OR=2,55), spray nasal de nicotina (2,37), inhalador bronquial de nicotina (2.18), bupropión (2.12), parche de nicotina (1.88) y chicle de nicotina (1.65). Todas las diferencias entre el placebo y el tratamiento fueron estadísticamente significativas. Seis estudios que incluían 1.881 pacientes compararon directamente vareniclina con bupropión y arrojaron resultados a favor de vareniclina (OR= 2.18; INTERVALO DE CONFIANZA DEL 95% [IC95%]: 1,09-4,08). Conclusiones. Vareniclina, bupropión y 5 formas de reemplazo nicotínico estudiadas (chicle, parche, spray nasal, tabletas e inhaladores) fueron más efectivos que placebo al promover una terapia para dejar de fumar. A pesar de la eficacia documentada, el número absoluto de pacientes abstinentes a 12 meses es bajo.