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.

A Systematic Review on Effectiveness of Nicotine-Based and NonNicotine Based Drug Delivery System for Smoking Cessation Among the Elderly

@#Introduction: Smoking is associated with a higher risk of mortality, especially in smokers with cardiovascular and respiratory diseases. Smoking cessation remains the most effective approach in reducing smoking-related illness risks at all ages. For elderly smokers, smoking cessation has been proved to prolong life expectancy and reduce the risk of stroke and ischemic heart disease. However, a wide selection of smoking cessation medications makes prescribing challenging, especially among elderly smokers. Inability to recommend the best treatment may reduce the smoking cessation success rate in the elderly. Therefore, this study compares the effectiveness of pharmacotherapy available and correlate the effect of ageing on the effectiveness, leading to the recommendation of the best medication for elderly smokers. Method: A systematic searching strategy was performed in three different databases by using predetermined search strings. Results: Overall, this systematic review revealed that varenicline showed the greatest smoking cessation rate among the elderly, followed by bupropion and NRT. Conclusion: It is suggested that varenicline offered the best medical aid for smoking cessation in the elderly.

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.

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.

Determination of UV-Vis Spectrophotometric Method of Metal Complexes Stoichiometry between Cu(II), Ca(II), Cd(II), Mg(II) and Zn(II) with Bupropion Hydrochloride

In this study, simple, rapid and accurate UV-Vis spectrophotometric method was developed for the determination ofcomplexes stoichiometry of Cu(II)-bupropion hydrochloride, Ca(II)-bupropion hydrochloride, Cd(II)-bupropionhydrochloride, Mg(II)-bupropion hydrochloride and Zn(II)-bupropion hydrochloride. The spectrums of the complexesformed between bupropion hydrochloride with Cu (II), Ca (II), Cd (II), Mg (II) and Zn (II) metal cations were taken in therange of 500 to 190 nm and the stoichiometry of the complexes formed between bupropion hydrochloride with Cu (II), Ca(II), Cd (II), Mg (II) and Zn (II) metal cations were determined by using the mole ratio method at maximum wavelength(λmax=252 nm). The stoichiometry of Cu(II)-bupropion hydrochloride, Ca(II)-bupropion hydrochloride, Cd(II)-bupropionhydrochloride and Zn(II)-bupropion hydrochloride were calculated as 1:1, but Mg(II)-bupropion hydrochloride complexwas calculated as 1:2. The recovery was found 95.0% for bupropion hydrochloride. Lambert-Beer’s obeyed theconcentration range of 1.40-6.91 µg/mL for bupropion hydrochloride. The LOD and LOQ were found to be 13.81 and 1.38µg/mL for bupropion hydrochloride, respectively. The interaction between bupropion hydrochloride with Cu (II), Ca (II), Cd(II), Mg (II) and Zn (II) were investigated by applying UV-visible spectrophotometric method, and satisfactory results wereobtained

A study on the real world effect of the combination of bupropion hydrochloride sustained release tablets with behavior intervention on smoking cessation / 中国实用内科杂志

OBJECTIVE: To discuss the real world effect of bupropion hydrochloride sustained-release tablets and psychological intervention as well as WeChat publicity and follow-up on smoking cessation. METHODS: Totally 283 subjects were divided into two groups according to their own wishes: 84 people chose WeChant and psycholigical intervention, and were defined as control group; 199 people chose bupropion hydrochloride and WeChant and psycholigical intervention, and were defined as treatment group. The one-month smoking cessation rate and weight changes of the two groups in 3 months was compared, and the factors affecting the smoking cessation rate were analyzed. RESULTS: The success rate was 57.8% in treatment group, and the success rate of the control group was 10.7%. There was a statistically significant difference between the two groups. The average weight gain was 2.6 kg in the treatment group, and in the control group it was 3.5 kg, with no statistically significant difference. The presence of depression, intervention pattern, smoking-related disease, the number of cigarettes smoked per day, and the need to quit smoking for family members and the readiness to quit were statistically siginificant factors. The faliure rate of smoking cessation in depressed smokers was 7.772 times that of non-derpessed smokers, and it was4.492 times that of people with smoking related deseases. The failure rate of smoking cessation in people smoking more than20 cigarettes a day was 4.090 times that of pepople smoking less than 20. The failure rate in smokers without family requests of quiting smoking was 0.463 times that of those with requests; the failure rate in smokers without readiness was0.274 times that of those with proper readiness. The failure rate in control group was 14.292 times that of the treatment group. CONCLUSION: Bupropion hydrochloride sustained-release tablets + psychological intervention + WeChat platform promotion can significally increase the rate of sucessful smoking cessation. Factors affecting the success rate of smoking cessation are depression, intervention methods, smoking-related deseases, the number of cigarettes smoked, family requirements and smoking cessation preparations.

Augmentation of Aripiprazole versus Bupropion on Specific Symptoms of Depression in Older Adult Patients : A Post-Hoc, Multi-Center, Open-Label, Randomized Study / 생물치료정신의학

OBJECTIVES: The purpose of this study was to compare aripiprazole versus bupropion augmentation therapy in older adult patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors(SSRIs).METHODS: This is a post-hoc analysis of a 6-week, randomized prospective open-label multi-center study in thirty older adult patients with major depressive disorder. Participants were randomized to receive aripiprazole(N=16, 2.5–10mg/day) or bupropion(N=14, 150–300mg/day) for 6 weeks. Montgomery Asberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating scale(HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales(anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: There was a significantly greater decrease in MADRS scores in aripiprazole group compared to bupropion group at 4(p<0.05) and 6(p<0.05) weeks. There were significantly higher response rate at week 4(p<0.05) and 6(p<0.05) and remission rate at week 6 in aripiprazole group compared to bupropion group. Individual HAM-D17 items showing significantly greater change with adjunctive aripiprazole than bupropion: insomnia, late(ES=0.81 vs. −0.24, p=0.043), psychomotor retardation(ES=1.30 vs. 0.66, p=0.024), general somatic symptoms(ES=1.24 vs. 0.00, p=0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than bupropion with respect to mean change for drive(p=0.005).CONCLUSION: Results of this study suggested that aripiprazole augmentation have superior efficacy in treating general and core symptoms of depression in older adult patients. Aripiprazole augmentation is associated with greater improvement in specific symptoms of depression such as psychomotor retardation, general somatic symptoms and drive.

Effectiveness and Safety of Bupropion in Children and Adolescents with Depressive Disorders: A Retrospective Chart Review

OBJECTIVE: This study aimed to investigate the effectiveness and safety of bupropion extended-release for the treatment of depressive disorder in children and adolescents. METHODS: This was a 12-week, retrospective chart review of bupropion, which included 127 youth (age, 15.3 ± 2.3 years; 66 boys) with depressive disorders (105 with major depressive disorder, 14 with dysthymia, 11 with adjustment disorder with depressed mood, and seven with depressive disorder not otherwise specified). Illness severity at baseline and at the 4th, 8th, and 12th weeks was retrospectively scored using the Clinical Global Impressions-Depression-Severity (CGI-Depression-S) and/or Clinical Global Impressions-Depression-Improvement (CGI-Depression-I). RESULTS: The mean dose of bupropion was 180.0 ± 52.6 (range, 75–300) mg/day and the mean duration 33.9 ± 53.1 (range, 7–295) weeks. The CGI-Depression-S scores were significantly decreased over 12 weeks (F = 132.125, p < 0.001, partial η² = 0.508). Fifty-eight subjects (45.7%) were determined to be responders at 12 weeks (defined by a CGI-Depression-I score ≤ 2). Forty-six patients (36.2%) discontinued bupropion before the 12 weeks (19 due to adverse events, 15 due to poor effectiveness, three due to referral to other clinics, and nine due to follow-up loss for unknown reasons). Overall, bupropion was well tolerated. The most common adverse event was irritability (n = 12, 9.4%), which resolved spontaneously in eight subjects or after drug discontinuation in four subjects. CONCLUSION: Our results provide preliminary evidence of the effectiveness and safety of bupropion in children and adolescents with depressive episodes. Large, prospective, placebo-controlled studies are needed to confirm these findings.

Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.

Comparative study of acupoint catgut embedding and bupropion hydrochloride sustained-release tablets for tobacco dependence / 中国针灸

OBJECTIVE@#To compare the clinical efficacy of acupoint catgut embedding and bupropion hydrochloride sustained-release tablets in the treatment of tobacco dependence.@*METHODS@#A total of 100 patients with tobacco dependence who met the inclusion criteria were randomly divided into an acupoint catgut embedding group and a drug group, 50 cases in each group. In the acupoint catgut embedding group, acupoint catgut embedding was applied at Xinshu (BL 15), Shenmen (HT 7), Tianmei (Extra), Taichong (LR 3), the treatment was given once every 2 weeks for 4 times; The bupropion hydrochloride sustained-release tablets was orally administered in the drug group for 7 weeks, 150 mg each time, once a day for the first 3 days, twice daily from day 4 to day 7, and once a day after day 8. The Fagerström test for nicotine dependence (FTND) score before and after treatment, the 4th and 8th week smoking cessation rate, the continuous smoking cessation rate and efficacy, compliance rate and adverse reaction rate were compared in the two groups.@*RESULTS@#A total of 100 patients were enrolled, and 97 patients completed the study (loss rate was 3%), including 49 cases in the acupoint catgut embedding group and 48 cases in the drug group. The FTND scores in the two groups were lower than those before treatment (both 0.05). At the 4th and the 8th week, the smoking cessation rate in the acupoint catgut embedding group was 40.8% (20/49) and 79.6% (39/49) respectively, the smoking cessation rate in the drug group was 41.7% (20/48) and 83.3% (40/48) respectively, the two groups were equally effective (both >0.05). The continuous smoking cessation rate in the acupoint embedding group was 40.8% (20/49), which was equivalent to 41.7% (20/48) in the drug group (>0.05). The rate of complete compliance in the acupoint embedding group was 61.2% (30/49), which was significantly better than 37.5% (18/48) in the drug group (<0.05). The adverse reaction rate in the acupoint catgut embedding group was 12.2% (6/49), which was significantly lower than 29.2% (16/48) in the drug group (<0.05).@*CONCLUSION@#Acupoint catgut embedding can effectively improve the symptoms of tobacco dependence after smoking cessation. Its curative effect is close to that of bupropion hydrochloride sustained-release tablets, and it has good clinical compliance and less adverse reactions.

Understanding the Mechanism of Action and Clinical Implications of Anti-Obesity Drugs Recently Approved in Korea / 가정의학회지

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.

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.

A study of the outcome of Nicotine use disorder treatment devised as per an evidence-based treatment protocol

Introduction: Tobacco is the most common form of nicotine. It is smoked most commonly in cigarettes,then, in descending order, cigars, snuff, chewing tobacco, and in pipes. Effective treatments have now beenidentified and should be used with every current and former smoker. Guidelines that are available mightnot be specific and tailor made for patient population we come across. Hence, we reviewed and criticallyappraised available guidelines, systemic reviews, meta-analysis, review articles etc and we designed ourevidence-based treatment protocols accordingly and this study will test the treatment effectiveness innicotine use disorder.Material & Methods: It was a prospective observational study. Individuals aged above 18 years withnicotine use disorder were enrolled into the study. The participants were assessed using structuredPerforma including demographic data, quit attempts and severity of Nicotine dependence using theFagerström Nicotine Dependence Scale. Group A includes participants who were given Bupropion andGroup B were given varenicline. Follow up was done at 1 and 3 month and patients assessed for relapse.Results: Out of 90 participants 40 patients dropped out and 50 patients who completed the study, at 1month of follow up there was no significant difference in relapse between two groups but at 3 monthsfollow up compared to Group B (Varenicline), in group A (Bupropion) number of relapse is significantlyhigher (p value = 0.044).Conclusion: At the end of the 3 months, significant difference was found between the medications interms of the success of smoking cessation. Patients taking Bupropion had significantly higher relapse rateas compare to varenicline.

Comparison of the Bupropion versus Aripiprazole Adjunctive Therapy for the Treatment of Female Depression : Post-Hoc Analyses from a Randomized Prospective Open-Label Multi-Center Study / 우울ㆍ조울병

OBJECTIVES: The purpose of this study was to examine effects of adjunctive aripiprazole versus bupropion, on depressive symptoms of female depression.METHODS: Sixty six female patients with major depressive disorders were enrolled from a six-week, randomized prospective open-label multi-center study. Participants were randomized to receive aripiprazole (2.5–10 mg/day) or bupropion (150–300 mg/day). Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale (HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales (anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: Overall, both treatments improved depressive symptoms, without causing serious adverse events. There were significant differences in the HAM-D17 total score (p=0.046) and CGI-S (p=0.004), between aripiprazole and bupropion augmentation, favoring aripiprazole over bupropion. Aripiprazole revealed significantly greater effect size in depressed mood (p=0.006), retardation (p=0.005), anxiety psychic (p=0.032), and general somatic symptom (p=0.01).CONCLUSION: While both treatments were effective, results of this study suggested that aripiprazole may be preferable, in treating general and core symptoms of female depression.

National Trends in Smoking Cessation Medication Prescriptions for Smokers With Chronic Obstructive Pulmonary Disease in the United States, 2007-2012 / 예방의학회지

OBJECTIVES: Smoking cessation decreases morbidity and mortality due to chronic obstructive pulmonary disease (COPD). Pharmacotherapy for smoking cessation is highly effective. However, the optimal prescription rate of smoking cessation medications among smokers with COPD has not been systemically studied. The purpose of this study was to estimate the national prescription rates of smoking cessation medications among smokers with COPD and to examine any disparities therein. METHODS: We conducted a retrospective study using National Ambulatory Medical Care Survey data from 2007 to 2012. We estimated the national prescription rate for any smoking cessation medication (varenicline, bupropion, and nicotine replacement therapy) each year. Multiple survey logistic regression was performed to characterize the effects of demographic variables and comorbidities on prescriptions. RESULTS: The average prescription rate of any smoking cessation medication over 5 years was 3.64%. The prescription rate declined each year, except for a slight increase in 2012: 9.91% in 2007, 4.47% in 2008, 2.42% in 2009, 1.88% in 2010, 1.46% in 2011, and 3.67% in 2012. Hispanic race and depression were associated with higher prescription rates (odds ratio [OR], 5.15; 95% confidence interval [CI], 1.59 to 16.67 and OR, 2.64; 95% CI, 1.26 to 5.51, respectively). There were no significant differences according to insurance, location of the physician, or other comorbidities. The high OR among Hispanic population and those with depression was driven by the high prescription rate of bupropion. CONCLUSIONS: The prescription rate of smoking cessation medications among smokers with COPD remained low throughout the study period. Further studies are necessary to identify barriers and to develop strategies to overcome them.

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. Palabras clave: Guías de práctica clínica, vareniclina, bupropión, nicotina, cesación 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. Keywords: clinical practice guidelines, varenicline, bupropion , nicotine, 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.