Profiling the combination of bupropion and dextromethorphan as a treatment option for major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. AREAS COVERED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. EXPERT OPINION: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.

Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING.

INTRODUCTION: Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed. METHODS: This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy. RESULTS: Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained. CONCLUSIONS: Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment. CLINICAL TRIAL IDENTIFIER: NCT03362099.

Evaluación en la vida real de la combinación naltrexona y bupropion para el tratamiento de adultos con sobrepeso y obesidad / Real-life evaluation of the combination naltrexone and bupropion for the treatment of overweight and obese adults

Objetive: Overweight and obesity represent a global epidemic of increasing prevalence associated with an increase in morbidity and mortality. In clinical trials, the combination of naltrexone/bupropion (NB), together with a hypocaloric diet and exercise, was superior to placebo in achieving a sustained reduction of body weight (BW). The purpouse of our investigation was to evaluate the clinical benefit of NB in reallife conditions. Methods: Ambispective and observational research, in a 225 patient's cohort with obesity, or overweight plus related comorbidities, under usual medical care and 16-week follow-up period. The management of the patients was under the usual conditions of practice, therefore, the performance of any diagnostic or therapeutic procedure was not imposed. Results: Unlike clinical trials, we included patients > 65 years old, with a body mass index (BMI) > 45 kg/m2, and type 2 diabetes mellitus (T2DM). NB was associated with significant reduction of baseline BMI (-3.1 kg/m2, IC 95%: -2.8 to -3.4, p < 0.0001) was observed, and 65% of the patients achieved a ≥5% reduction of their BW, despite lower medication compliance and the use of lower doses than the ones recommended. Conclusion: NB was effective and well tolerated to induce an initial reduction in BW. These results were similar to those reported in clinical trials in the same follow-up period, and even better than the ones observed in retrospective, real-life trials.

Objetivo: El sobrepeso y la obesidad representan una epidemia global de prevalencia creciente, asociada con aumento de la morbilidad y la mortalidad. En los ensayos clínicos centrales, la combinación de naltrexona/bupropion (NB), junto con una dieta hipocalórica y ejercicio, fue superior al placebo para lograr una reducción sostenida del peso corporal (PC). El propósito de nuestra investigación fue evaluar el beneficio clínico de la NB en pacientes con sobrepeso/obesidad en las condiciones de la vida real. Métodos: Investigación ambispectiva y observacional, en una cohorte de 225 pacientes con obesidad o sobrepeso más comorbilidades relacionadas, bajo atención médica habitual y un seguimiento de 16 semanas. El abordaje de los pacientes fue en las condiciones habituales de la práctica, por lo tanto, no se impuso la realización de procedimiento diagnóstico o terapéutico alguno. Resultados: A diferencia de los ensayos clínicos, se incluyeron pacientes > 65 años, con un índice de masa corporal (IMC) > 45 kg/m2 y diabetes mellitus tipo 2 (DBT2). La combinación NB se asoció con una reducción significativa del IMC inicial (-3.1 kg/m2; intervalo de confianza del 95% [IC 95%]: -2.8 a -3.4, p < 0.0001) y el 65 % de los pacientes logró una reducción ≥ 5% de su PC, a pesar de tener menor cumplimiento del tratamiento y del uso de dosis inferiores a las recomendadas. Conclusión: La combinación NB fue efectiva y bien tolerada para inducir una reducción inicial del PC. Estos resultados fueron similares a los informados en ensayos clínicos en el mismo período de seguimiento, e, incluso, mejores que los observados en estudios retrospectivos de la práctica clínica real.

Environmental enrichment affects behavioral and pharmacological response to antidepressants in CF1 mice.

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.

Tratamiento del tabaquismo guiado por marcadores genéticos

Introducción: Entre las adicciones por drogas, el tabaquismo ocupa el primer lugar como causa de morbimortalidad y es factor de riesgo para seis de las ocho principales causas de muerte en el mundo. La nicotina es el principal componente adictivo del tabaco. En la terapia de reemplazo con nicotina (TRN), la vareniclina y el bupropion son los medicamentos aprobados para tratamiento del tabaquismo, pero los resultados de las clínicas de dejación del tabaquismo sugieren que aún se desconoce muchas variables influyentes en la respuesta al tratamiento. Objetivo: Determinar la adherencia, la tolerabilidad y la efectividad de un programa de dejación de tabaquismo basado en nicotina o bupropion, en pacientes con dependencia al tabaco, seleccionados según los genotipos de las enzimas que metabolizan los dos fármacos. Hallazgos clínicos: Se incluyeron en esta serie 21 fumadores, 67% hombres, con edad promedio de 46,2±11,7 años. Su tabaquismo comenzó a los 17,8±6 años y llevaban fumando 28±13 años. Al inicio del estudio fumaban 17±12 cigarrillos por día (CPD), habían hecho 3,7±2 intentos de dejar de fumar y el puntaje NDSS (escala breve de evaluación de dependencia de la nicotina, por sus siglas en inglés) fue de 22±5 (punto de corte para dependencia a nicotina: 11 o más puntos). Tratamiento: Los pacientes tenían libre acceso telefónico al médico tratante y, cada semana, una consulta consistente en consejería y control del tratamiento farmacológico prescrito según los genotipos CYP2A6 (que codifica la enzima que metaboliza la nicotina) y CYP2B6 (que codifica la enzima que metaboliza el bupropion). Se empleó nicotina en parches transdérmicos de 14 mg el primer mes y luego de 7 mg el segundo mes, complementados con chicles para manejo del síndrome de abstinencia y bupropion en forma de liberación regulada por 300 mg, 1-2 veces al día. Resultados: Después de 8 semanas de tratamiento y 4 de observación, 15 sujetos (71,4%) respondieron en forma parcial/total. El consumo de CPD bajó de 17±12 al inicio del estudio, a 2,2±3,5 al final del estudio, que corresponde a una reducción de 195 cigarrillos/día. Siete de ocho pacientes tratados con bupropion (87,5%) y siete de trece tratados con nicotina (54%) tuvieron respuesta parcial/total. Solo un paciente formulado con nicotina suspendió el medicamento por intolerancia gastrointestinal (náusea y vómito). La tasa de recaídas, evaluada un mes después del tratamiento farmacológico, fue de cero. Se encontró buena correlación genotipo-fenotipo en los individuos tratados con bupropion, pero no en los tratados con nicotina. Relevancia clínica: La inclusión de marcadores farmacogenéticos para la elección de nicotina o bupropion en un programa de dejación de tabaquismo puede mejorar la adherencia, la tolerabilidad al fármaco y la efectividad del tratamiento.

Introduction: Among drug addictions, smoking ranks first as a cause of morbidity and mortality and is a risk factor for six of the eight leading causes of death in the world. Nicotine is the main addictive component of tobacco. In nicotine replacement therapy (NRT), varenicline and bupropion are the approved medications for smoking cessation, but results from smoking cessation clinics suggest that many variables influencing response to treatment remain unknown. Objective: To determine the adherence, tolerability and effectiveness of a smoking cessation program based on nicotine or bupropion, in patients with tobacco dependence, selected according to the genotypes of the enzymes that metabolize the two drugs. Clinical findings: Twenty-one smokers were included in this series, 67% men, with a mean age of 46.2 ± 11.7 years. Their smoking began at 17.8±6 years and they had been smoking for 28±13 years. At baseline, they smoked 17±12 cigarettes per day (CPD), had made 3.7±2 quit attempts, and the NDSS score it was 22±5 (cut-off point for nicotine dependence: 11 or more points). Treatment: The patients had free telephone access to the treating physician and, every week, a consultation consisting of counseling and control of the pharmacological treatment prescribed according to the CYP2A6 genotypes (encoding the enzyme that metabolizes nicotine) and CYP2B6 (coding for the enzyme that metabolizes bupropion). Nicotine was used in transdermal patches of 14 mg the first month and then 7 mg the second month, supplemented with gum to manage the withdrawal syndrome and bupropion in the form of controlled release 300 mg, 1-2 times a day. Results: After 8 weeks of treatment and 4 weeks of observation, 15 subjects (71.4%) responded partially/totally. CPD consumption dropped from 17±12 at the beginning of the study to 2.2±3.5 at the end of the study, which corresponds to a reduction of 195 cigarettes/day. Seven of eight patients treated with bupropion (87.5%) and seven of thirteen treated with nicotine (54%) had a partial/total response. Only one patient receiving nicotine discontinued the medication due to gastrointestinal intolerance (nausea and vomiting). The relapse rate, assessed one month after drug treatment, was zero. Good genotype-phenotype correlation was found in individuals treated with bupropion, but not in those treated with nicotine. Clinical relevance: The inclusion of pharmacogenetic markers for the choice of nicotine or bupropion in a smoking cessation program may improve adherence, drug tolerability, and treatment effectiveness.

Naltrexone/bupropion modifies weight, food intake, and Drd2 gene expression in rats.

Obesogenic diets are known to induce obesity and changes in food intake in experimental animals. Obesity negatively affects the peripheral metabolism and neural aspects, such as changes in eating behavior. In obese animals, dopamine (DA) receptor levels are reduced. DA is one of the main peptides involved in the motivation and pleasure of eating. A combination of naltrexone/bupropion (NB) has shown promise in controlling metabolic alterations, but there are few studies on how they modulate dopaminergic expression. NB, in addition to reducing food intake and body weight, can modify tyrosine hydroxylase (Th) and DA receptor D2 (Drd2) levels in the mesolimbic areas of rats submitted to a high-fat diet (HF). The study evaluated the effect of NB on food intake, body weight, and expression levels of Th, Drd1a, and Drd2, in the nucleus accumbens and striatum of rats fed on HF diet. Wistar rats were grouped according to diet: standard (n = 20) and HF diet (n = 20). The food intake and body weight were analyzed. The gene expression of Th, Drd1a, and Drd2 was evaluated using real-time PCR. NB combination of 1 mg/kg and 20 mg/kg reduced food intake and body weight, increased Drd2 expression in rats on HF diet, and increased Th in rats on both experimental diets. The level of Drd1a was unchanged. We concluded that bodyweight reduction may be associated with decreased food intake in response to the increased Drd2 expression in the mesolimbic areas of rats that received an HF diet.

Cost-Effectiveness Analysis of Varenicline Versus Currently Funded Smoking Cessation Strategies in Brazil.

OBJECTIVES: To assess the cost-effectiveness of varenicline in comparison to currently funded smoking cessation strategies in Brazil. METHODS: We modeled the lifetime direct costs and health-related quality of life of a hypothetical cohort of smokers with a single attempt to quit smoking using one of the following: (1) cognitive behavioral therapy (CBT) without any pharmacological intervention, (2) varenicline, (3) bupropion, (4) nicotine replacement therapy (NRT) with transdermal patch, (5) bupropion in combination with NRT transdermal patch, and (6) combined NRT (oral plus transdermal). All drug alternatives were considered with concomitant CBT. The analysis relied on a Markov model based on the Benefits of Smoking Cessation and Outcomes study and used different age and sex categories in the consideration of relative risks and incidence rates of the diseases included in the model. The analysis was conducted from the healthcare system perspective, and a 3% discounting rate for costs and outcomes was applied. Model parameter values were sourced from published literature. Probabilistic and deterministic sensitivity analyses assessed robustness. RESULTS: Among the smoking cessation alternatives available in Brazil, varenicline and combined NRT were estimated to have higher effectiveness; varenicline, however, was dominated due to its higher average cost. In the base-case analysis, combined NRT had an incremental gain of 0.25 quality-adjusted life-years (QALYs) in comparison to the second-best option (bupropion in combination with NRT transdermal patch) and an incremental cost-effectiveness ratio of R$2173.47/QALY ($595.45/QALY). CONCLUSIONS: Combination of oral and transdermal NRT (coupled with CBT) was the most effective smoking cessation option and was 100% cost-effective within a conservative willingness-to-pay threshold.

Effects of topiramate, bupropion and naltrexone isolated or combined on subcutaneous adipose tissue in obese rats

ABSTRACT Objective: To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue. Methods: A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes. Results: The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant. Conclusion: The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.

[Manejo de la cesación tabáquica entre residentes de cardiología de Iberoamérica]. / Smoking cessation management among Iberoamerica's cardiology residents

Introduction and objectives: Although cardiologists frequently assist patients who suffer damage from smoking, the degree of training they receive to manage this problem during their residency is unknown. Because of this, we'd proposed to ­evaluate the preferences and practices of cardiology residents for smoking cessation of the attending patients. Materials and methods: Closed, prefixed, voluntary and anonymous survey among doctors who carried out the specialty of cardiology in 5 countries of Latin America and Spain. Results: 716 residents were surveyed; 62.4% from Argentina, 19% from Mexico, 6.8% from Spain, 6.7% from Chile, 3.2% from Uruguay, and 1.9% from Paraguay. When asked about the importance they assigned to this problem (using a scale of 1-10), 85.8% assigned this question a score of 8 or higher. While 80.5% of the participants expressed giving short anti-tobacco advice routinely, only 27.7% used pharmacological therapy for this purpose. Among those who did not use pharmacological therapy, 58.3% said that the reason was not being familiar with the treatments; 62.9% of the surveyed said they had not received any type of training in this problem. Those residents who received some type of training reported feeling more prepared for this (p < 0.0001). Conclusion: We found that cardiology residents have a low knowledge of pharmacological treatment and relatively low confidence to provide assistance in smoking cessation. This topic should be included in the training of future cardiologists in order to achieve a more comprehensive cardiovascular prevention.

Introducción y objetivos: Si bien los cardiólogos asisten cotidianamente a pacientes que sufren daño por el tabaquismo, no se conoce el grado de formación que reciben sobre esta problemática durante su residencia. Debido a ello nos propusimos evaluar las preferencias y prácticas de los residentes de cardiología para la cesación tabáquica de los pacientes que asisten. Materiales y métodos: Encuesta cerrada, prefijada, voluntaria y anónima entre médicos que realizaban la especialidad de cardiología en cinco países de Latinoamérica y España. Resultados: Se encuestaron 716 residentes: un 62.4% de Argentina, un 19% de México, un 6.8% de España, un 6.7% de Chile, un 3.2% de Uruguay y un 1.9% de Paraguay. Con respecto a la importancia que asignaban a esta problemática (empleando una escala de 1-10), el 85.8% le asignó a esta pregunta una puntuación de 8 o mayor. Mientras el 80.5% de los participantes expresó dar consejo breve antitabáquico sistemáticamente, solamente un 27.7% empleaban terapia farmacológica con este fin. Entre quienes no empleaban terapia farmacológica, el 58.3% manifestó que el motivo era no encontrarse familiarizados con los tratamientos. El 62.9% de los encuestados dijo no haber recibido ningún tipo de formación en esta problemática. Aquellos residentes que recibieron algún tipo de formación manifestaron sentirse más preparados (p < 0.0001). Conclusión: Encontramos un bajo conocimiento sobre el tratamiento farmacológico y relativamente poca seguridad por parte de los residentes de cardiología para brindar asistencia en cesación tabáquica. Consideramos esencial incluir este tópico en la formación de los futuros cardiólogos a fin de lograr una prevención cardiovascular más integral.

Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses.

Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B-N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B-N versus control with reported incidence of MACE. The meta-analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient-years who were randomized to an active treatment (bupropion [n = 2965] or B-N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m2 . The additive network meta-analysis model for random effects showed no association between bupropion, B-N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65-1.25], p = 0.52; OR = 0.97 [95%CI 0.75-1.24], p = 0.79; OR = 1.08 [95%CI 0.71-1.63], p = 0.73, respectively; I2 = 0%, p = 0.86). Meta-regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two-tailed) for non-inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B-N is not associated with the incidence of MACE as compared with placebo.

Degradation of antidepressant pharmaceuticals by photoperoxidation in diverse water matrices: a highlight in the evaluation of acute and chronic toxicity.

Photoperoxidation (UV/H2O2) was used to degrade three of the worldwide most consumed antidepressant pharmaceuticals-bupropion, escitalopram, and fluoxetine-in ultrapure water, drinking tap water, surface water, and reclaimed water. The study was performed with antidepressants in concentration levels in which these compounds usually occur in the water matrices. Online solid-phase extraction coupled to UHPLC-MS/MS was used to quantify the analytes during degradation studies. The UV/H2O2 process was able to degrade bupropion and fluoxetine in ultrapure water, using 0.042 mmol L-1 of H2O2 and 1.9 kJ of UV-C irradiation. Nevertheless, escitalopram, which had the most recalcitrant character among the studied antidepressants, needed a tenfold more oxidant and UV-C irradiation. The primary metabolites of the antidepressants were identified as the major by-products generated by the UV/H2O2 process, and they persisted in the solution even when the parent compound was degraded. The residual toxicity of the solution was evaluated for two different trophic levels. The UV/H2O2 process reduced the toxicity of the solution to Raphidocelis. subcapitata microalgae after 30 min of reaction. On the other hand, the toxicity of the residual solution increased over the reaction time to the marine bacteria Vibrio fischeri (reaching up to 48.3% of bioluminescence inhibition after 60 min of reaction). Thus, our results evidenced that the toxicity against different trophic levels and the monitoring of the by-products formed are important aspects to be considered regarding the safety of the treated solution and the optimization of the treatment process.

Bupropion in dermatology: A brief update.

There is currently an interest in evaluating the role that antidepressants may play in the treatment of primary cutaneous disorders. It has been proposed that antidepressants could have anti-inflammatory effects, but the clinical relevance of this effect has not been adequately established. In the case of bupropion, evidence for its specific use in dermatologic conditions currently come only from a pilot study and a case report. While this level of evidence is unlikely to be sufficient to guide clinical practice, the authors of this brief update hope to sort the available information to serve as a guide and provide a structure for future research.

Intoxicaciones por bupropión: presentación de caso / Bupropion toxicity: a risk to consider

Resumen En Colombia las intoxicaciones autoinfligidas vienen en aumento en los últimos años, la principal causa son los medicamentos y dentro de éstos, los psicofármacos. El bupropión es un antidepresivo, inhibidor débil de la recaptación de dopamina y noradrenalina; está aprobado para el tratamiento del trastorno depresivo mayor y se ha utilizado en otras indicaciones como: depresión bipolar, abandono del cigarrillo, trastorno por déficit de atención e hiperactividad (TDAH), obesidad y disfunción sexual. Sus principales efectos adversos son cardiovasculares y neurológicos. Esta serie de casos busca evidenciar las complicaciones asociadas a su toxicidad y resaltar algunos aspectos en el manejo de estas intoxicaciones; tales como el uso de la irrigación gastrointestinal y el uso de emulsiones lipídicas. MÉD. UIS. 2020;33(2):117-121.

Abstract In Colombia, self-inflicted drug poisonings have been increasing in recent years, and within these, psychotropic drugs. The vast majority of psychoactive drug poisonings are explained by SSRI tricyclic antidepressants and anticonvulsants. Bupropion is an antidepressant, dopamine and norepinephrine reuptake inhibitor; approved for the treatment of major depressive disorder and used in other indications such as: bipolar depression, smoking cessation, attention deficit disorder the importance of this series of cases is to sensitize health personnel about the increase in prescription and therefore more Toxicity risks associated with this medicine. There is little literature on the management of bupropion toxicity, understanding these and it is important to highlight its amphetamine-like structure that explains neurological risks such as seizures and cardiovascular events as arrhythmias, although it is true that there is no consensus on the management, it is worth highlighting the usefulness of lipid emulsions This series of cases, being the first in Colombia, seeks to highlight the complications associated with its toxicity and highlight some aspects in the management of this poisoning; such as the use of gastrointestinal irrigation and the use of lipid emulsions. MÉD.UIS. 2020;33(2):117-121.

Supraversión de la mirada en intoxicación mortal por bupropión / Sustained upgaze in a patient who ingested high doses of bupropion: report of one case

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Guías de Práctica Clínica para el Tratamiento del Tabaquismo / Clinical Practice Guidelines for Smoking Cessation

Resumen: Considerando que la población chilena tiene una historia de alto consumo de tabaco, la Sociedad Chilena de Enfermedades Respiratorias en colaboración con las Sociedades Chilenas de Cardiología; Endocrinología y Diabetes formó un grupo interdisciplinario que emitió un conjunto de recomendaciones para el enfrentamiento del paciente fumador, asesorado metodológicamente por expertos. Estas intervenciones deben priorizarse en grupos de alto riesgo. Métodos: El panel elaboró y graduó las recomendaciones siguiendo la metodología GRADE. Para estimar el efecto de cada intervención, se identificó revisiones sistemáticas y estudios clínicos aleatorizados. Además, se realizó una búsqueda de estudios realizados con población chilena. Para cada una de las preguntas, el panel determinó la dirección y fuerza de la recomendación mediante una tabla de la Evidencia a la Decisión. Recomendaciones: Para todos los fumadores, el panel recomienda usar consejería breve sobre no intervención, consejería vía telefonía móvil sobre no intervención, y mensajes de texto sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos).Para los individuos motivados, con indicación de fármacos para dejar de fumar el panel recomienda terapia de reemplazo de nicotina sobre no intervención, bupropión sobre no intervención, vareniclina sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos).Discusión: Se emiten recomendaciones basadas en la evidencia para el tratamiento del tabaquismo.

Considering that the Chilean population has a high tobacco consumption history, the Chilean Association of Respiratory Diseases in collaboration with the Chilean Associations of Cardiology and Endocrinology and Diabetes, formed an interdisciplinary group, that 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 in 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 over non-intervention, using mobile telephone counseling over non-intervention, using text messages over non-intervention, (strong recommendation; moderate certainty in the evidence of the effects) For motivated individuals, with indication for pharmacological interventions for quitting smoking, the panel recommends using nicotine replacement therapy over non-intervention, using bupropion over non-intervention, using varenicline over non-intervention. (strong recommendation; moderate certainty in the evidence of the effects) Discussion: This clinical practice guidelines provides recommendations based on the current evidence for smoking cessation.

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

RESUMEN Considerando que la población chilena tiene una historia de alto consumo de tabaco la Sociedad Chilena de Enfermedades Respiratorias en colaboración con las Sociedades Chilenas de Cardiología; Endocrinología y Diabetes formó un grupo interdisciplinario que emitió un conjunto de recomendaciones para el enfrentamiento del paciente fumador, asesorado metodológicamente por expertos. Estas intervenciones deben priorizarse en grupos de alto riesgo. Métodos: El panel elaboró y graduó las recomendaciones siguiendo la metodología GRADE. Para estimar el efecto de cada intervención, se identificó revisiones sistemáticas y estudios clínicos aleatorizados. Además, se realizó una búsqueda de estudios realizados con población chilena. Para cada una de las preguntas, el panel determinó la dirección y fuerza de la recomendación mediante una tabla de la Evidencia a la Decisión. Recomendaciones: Para todos los fumadores, el panel recomienda usar consejería breve sobre no intervención, consejería vía telefonía móvil sobre no intervención, y mensajes de texto sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Para los individuos motivados, con indicación de fármacos para dejar de fumar el panel recomienda terapia de reemplazo de nicotina sobre no intervención, bupropión sobre no intervención, vareniclina sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Discusión: Se emiten recomendaciones basadas en la evidencia para el tratamiento del tabaquismo.

Considering that Chilean population has a high tobacco consumption history, 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.

Bupropión: una alternativa farmacológica en cesación tabáquica / Bupropion: a pharmacological alternative in smoking cessation

Resumen Hay muchas razones para el uso de antidepresivos en cesación tabáquica: 1) la falta de nicotina puede producir síntomas depresivos o precipitar un episodio depresivo grave; 2) la nicotina puede tener efectos antidepresivos que mantienen la adicción; 3) algunos antidepresivos tienen una acción en vías neuronales o receptores implicados en la adicción a la nicotina; y 4) algunos pacientes no desean usar otras terapias o han fracasado con ellas. Bupropión es terapia de primera línea para la cesación del tabaco, con efectividad a largo plazo, los efectos adversos graves son escasos. La evidencia sugiere que bupropión es de eficacia similar a la terapia de reemplazo de nicotina (TRN) y menos eficaz que vareniclina, pero se necesita más estudios para confirmar esto. Bupropión es seguro en pacientes psiquiátricos compensados en un periodo de tres meses o más.

There are many reasons for the use of antidepressants in smoking cessation: 1) lack of nicotine can produce depressive symptoms or precipitate a severe depressive episode; 2) nicotine may have antidepressant effects that maintain addiction; 3) some antidepressants have an action on neural pathways or receptors involved in nicotine addiction; and 4) some patients do not want to use other therapies or they have failed with them. Bupropion is first-line therapy for smoking cessation, with long-term effectiveness, serious side effects are rare. The evidence suggests bupropion is similar in effectiveness to nicotine replacement therapy (NRT), and less effective than varenicline, but more studies are needed to confirm this. Bupropion is safe in psychiatric patients compensated over a period of three months or more.

Vareniclina / Varenicline

Resumen Vareniclina es terapia de primera línea para la cesación del tabaquismo, y presenta la mayor efectividad demostrada ampliamente en ensayos clínicos logrando cifras de abandono al año del orden de 25-35%. En la más reciente revisión de efectividad realizada por la Cochrane se evaluaron 39 ensayos que randomizaban vareniclina contra placebo y en comparación con sustitutos de nicotina (TRN) y bupropión. Con vareniclina se objetivó un RR de 2,24 para abstinencia a 6 meses o más prolongado a dosis standard (2 mg al día) contra placebo. El RR de vareniclina versus placebo comparando con bupropión o TRN fue de 1,3 y 1,25 respectivamente mostrando su superioridad una vez más. Cuando se evaluó el uso de vareniclina por un periodo más prolongado que 12 semanas, se observó que la droga fue bien tolerada sugiriendo que es factible su uso sin intensificar los efectos adversos.

Varenicline is a first-line therapy cessation of smoking, and has the highest effectiveness widely demonstrated in clinical trials with drop-out figures per year of the order of 25-35%. In the most recent effectiveness review conducted by the Cochrane, 39 trials were evaluated that randomized varenicline versus placebo and compared with nicotine substitutes (NRT) and bupropion. With varenicline, a RR of 2.24 was observed for abstinence at 6 months or longer at standard doses (2 mg daily) versus placebo. The RR of varenicline versus placebo compared with bupropion or NRT was 1.3 and 1.25 respectively showing its superiority once again. When the use of varenicline was evaluated for a period longer than 12 weeks, it was observed that the drug was well tolerated suggesting that its use is feasible without intensifying the adverse effects.

Terapia combinada para el control de la dependencia a nicotina / Combination therapy for nicotine dependence control

Resumen La terapia combinada es la de mezcla de farmacos para al cesación del tabaquismo, tal como terapias de reemplazo nicotínico (TRN) en modalidad prolongada como es el parche junto a una modalidad de acción corta como puede ser chicle, goma, lozenge, pastillas o inhalador nasal), es decir dos o más fármacos aprobados y demostrados útlies para el cese del tabaco con o sin el apoyo de TRN. Es muy importante considerar la comorbilidad médica y psiquiatrica porque la población que persiste adicta es cada vez más compleja en términos de comorbilidades y elevado nivel adictivo. La mayor parte de las terapias combinadas usan TRN asociadas a bupropión o vareniclina. Existe evidencia sobre efectividad y seguridad de las TRN utilizadas entre ellas o en asociación a vareniclina o bupropión, sin embargo, la evidencia sobre seguridad en la modalidad combinada no es tan robusta como la que existe para cada fármaco en monoterapia, ya que los efectos adversos se suman de manera que se sugiere reservar las combinaciones para personas con alto nivel de adicción y/o con historia de fracaso en intentos previos con monoterapia. En suma, los fármacos de demostrada efectividad y seguridad como TRN, bupropión y vareniclina pueden usarse en combinación doble o triple, preferenciando el uso de TRN de corta acción cuando se adiciona a alguno de los fármacos orales para aliviar la ansiedad por fumar.

This therapy is a combination of medicines consisting of nicotine replacement therapy (NRT) using a prolonged modality such as the patch, along with a short-acting medicine such as chewing gum, lozenge, gum, or nasal inhaler). This means two or more drugs approved and demonstrated useful for cessation of smoking with or without the support of NRT. It is very important to consider medical and psychiatric comorbidity because the population that persists addicted is increasingly complex in terms of comorbidities and high addictive level. Most of the combination therapies use NRT associated with bupropion or varenicline. There is evidence on the effectiveness and safety of TRN used in both modalitres (long and short acting) in combination with varenicline or bupropion. However, safety evidence is not robust for the combination modality as it is for, each drug as monotherapy, since adverse effects are added so it is suggested to reserve the combinations for people with high level of addiction and / or history of failure in previous attempts with monotherapy. In summary, therapy with demonstrated effectiveness as NRT, bupropion and varenicline can be used in double or triple combination, prefering the use of short acting NRT added to one of the oral drugs to alleviate smoking anxiety.

Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy.

OBJECTIVES: The aim of this study was to investigate smoking treatment effectiveness and retention in a population with and without mental disorders (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine patch alone or in combination with other medications (i.e., gum, bupropion, or nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care Center unit (CAPS), taking into account sociodemographics and smoking profile covariates. METHODS: The study involved comparison of treatment success (seven-day point prevalence abstinence at the end of the treatment) and retention (presence of the individual in all of the four medical consultations and six group sessions) in two subsamples of patients with MD (n = 267) and without MD (n = 397) who were included in a six-week treatment provided by a CAPS from 2007 to 2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine patches, nicotine gums, and bupropion and nortriptyline available, prescribed by psychiatrists). RESULTS: Within patients with MD, CBT plus nicotine patch plus bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80, 95% CI [0.65, 0.99], p = .048) were associated with treatment success. No variable was associated with dropout or retention within patients with or without MD. CONCLUSION: Our findings support the use of CBT plus nicotine patch plus bupropion as well as CBT plus nicotine patch plus gum in samples with high rates of medical, psychiatric, and addiction disorders. These findings support those of previous studies in the general population. Pharmacological treatment associated with group CBT based on cognitive-behavioral concepts and combined with ongoing MD treatment seems to be the best option for smoking cessation treatment among patients with MD. Units that deal with patients with MD, such as CAPS in Brazil, should be encouraged to treat smoking addiction in this population. Future studies should investigate retention rates in other samples of patients with MD.