Clinical Presentations of Bupropion Prescription Drug Misuse: A Systematic Review.

BACKGROUND: Among prescribers, bupropion is considered a substance of low misuse potential, with some studies showing lesser misuse potential than caffeine. However, several case reports exist of recreational bupropion misuse and diversion. Our goal is to understand at-risk populations, clinical courses, interventions, and outcomes after acute ingestion of bupropion via oral, intravenous route, and insufflation. METHODS: The systematic review was registered with PROSPERO on August 5, 2023. We conducted a systematic literature search on July 30, 2023, utilizing 8 databases with the help of the Medical Subject Headings (MeSH) term "Bupropion" in the context of misuse and abuse. Ultimately, we found 17 articles with qualitative synthesis relevant to our study objective and meeting our inclusion/exclusion criteria. RESULTS: Bupropion insufflation and intravenous injection occur almost exclusively in patients with a substance use disorder history, with a preponderance of patients with stimulant use disorder or multiple substance use disorders. Additionally, many were dual-diagnosis patients with a history of attention deficit hyperactivity disorder and stimulant use disorder, treated with bupropion. Patients describe the effects of bupropion insufflation/IV injection as a milder "cocaine-like" high that is brief, with less severe withdrawal effects of anxiety and agitation. The most common side effect at presentation was tachycardia, followed by seizures responsive to IV benzodiazepines. IV injection seems particularly insulting to the vascular system, with cellulitis, tissue necrosis, and digital ischemia as documented adverse effects. CONCLUSIONS: This systematic review highlights the bupropion misuse potential in certain patient populations and serves to increase awareness among clinicians. Additional patient screening, monitoring and follow-up, surveillance, and further research are needed to investigate and prevent bupropion misuse in at-risk patient populations entirely.

Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.

AIM: To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity. MATERIALS AND METHODS: This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal. RESULTS: Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels. CONCLUSION: Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity.

Suicide ideation and male-female differences in major depressive disorder.

OBJECTIVE: This study aimed to explore male-female differences in suicide ideation (SI) and suicide risk factors in major depressive disorder (MDD). METHODS: We analysed 482 adults (sample 1) and 438 elderly outpatients (sample 2) with MDD. Sample 1 was treated with different antidepressant combinations (escitalopram; bupropion plus escitalopram; venlafaxine plus mirtazapine) and assessed by means of the Concise Health Risk Tracking (SI), Quick Inventory of Depressive Symptomatology, Altman Mania Rating Scale and Psychiatric Diagnostic Screening Questionnaire. Sample 2 was treated with venlafaxine and assessed using the Hamilton scale for depression, Anxiety Sensitivity Index and Penn State Worry Questionnaire for anxiety, Beck Scale for Suicide Ideation and Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: In sample 1, females had greater depression severity (O.R 0.961 99%CI: 0.929 - 0.995), males reported more alcohol abuse (O.R 1.299 99%CI: 1.118 - 1.509) and active SI (O.R 1.109 99%CI: 1.005 - 1.255). In sample 2 men showed more severe SI (O.R 1.067; 99%CI: 1.014 - 1.122) and weight loss (OR = 5.89 99%CI: 1.01 - 34.19), women more gastrointestinal symptoms. CONCLUSIONS: In these selected samples, although women had more severe depression, men had more suicide risk factors. Such differences might contribute to men's increased suicide risk.

In major depressive disorder sex differences affect the clinical expression of depressive episodes. In comparison to men, women endorse higher levels of overall depression in adult MDD and more somatic anxiety and gastrointestinal symptoms in late-life MDD.After controlling for confounding variables, males have more severe SI and a larger number of suicide risk factors (eg. alcohol abuse; weight loss). The association between male sex and SI is detectable in both adults and elderly patients with MDD.Further studies are necessary to elucidate how sex differences in suicide ideation and suicide risk factors are related to men's increased suicide risk.

Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). METHODS: We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. RESULTS: Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. CONCLUSIONS: A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.

Clinical Evaluation of the Effect of Encorafenib on Bupropion, Rosuvastatin, and Coproporphyrin I and Considerations for Statin Coadministration.

BACKGROUND AND OBJECTIVES: Encorafenib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma or metastatic colorectal cancer, respectively, with selected BRAF V600 mutations. A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of encorafenib on rosuvastatin, a sensitive substrate of OATP1B1/3 and breast cancer resistance protein (BCRP), and bupropion, a sensitive CYP2B6 substrate. Coproporphyrin I (CP-I), an endogenous substrate for OATP1B1, was measured in a separate study to deconvolute the mechanism of transporter DDI. METHODS: DDI study participants received a single oral dose of rosuvastatin (10 mg) and bupropion (75 mg) on days - 7, 1, and 14 and continuous doses of encorafenib (450 mg QD) and binimetinib (45 mg BID) starting on day 1. The CP-I data were collected from participants in a phase 3 study who received encorafenib (300 mg QD) and cetuximab (400 mg/m2 initial dose, then 250 mg/m2 QW). Pharmacokinetic and pharmacodynamic analysis was performed using noncompartmental and compartmental methods. RESULTS: Bupropion exposure was not increased, whereas rosuvastatin Cmax and area under the receiver operating characteristic curve (AUC) increased approximately 2.7 and 1.6-fold, respectively, following repeated doses of encorafenib and binimetinib. Increase in CP-I was minimal, suggesting that the primary effect of encorafenib on rosuvastatin is through BCRP. Categorization of statins on the basis of their metabolic and transporter profile suggests pravastatin would have the least potential for interaction when coadministered with encorafenib. CONCLUSION: The results from these clinical studies suggest that encorafenib does not cause clinically relevant CYP2B6 induction or inhibition but is an inhibitor of BCRP and may also inhibit OATP1B1/3 to a lesser extent. Based on these results, it may be necessary to consider switching statins or reducing statin dosage accordingly for coadministration with encorafenib. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03864042, registered 6 March 2019.

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

PURPOSE: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. METHODS: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. RESULTS: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. CONCLUSION: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

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)

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.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina / Methods for smoking cessation and treatment of nicotine dependence

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Smoking is related to 30 percent of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50 percent reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.

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.

Desenvolvimento e validação de método cromatográfico para o dosamento do cloridrato de bupropiona / Development and validation of a chromatographic method for the determination of bupropion hydrochloride

O cloridrato de bupropiona é utilizado no tratamento da depressão e também indicado no tratamento da dependência à nicotina.O objetivo deste estudo foi desenvolver e validar um método por cromatografia a líquido de alta eficiência (CLAE),alternativo ao oficial preconizado pela Farmacopéia Americana para a determinação quantitativa do cloridrato de bupropiona.O método difere do oficial por apresentar uma fase móvel simples, na qual não é necessária a utilização do solvente tetraidrofurano nem da solução tampão.Outra vantagem do método proposto é a de apresentar um tempo de retenção do fármaco relativamente curto.A estabilidade do fármaco frente a determinadas condições de estresse (hidrólise, oxidação e fotólise), também foi avaliada.O método mostrou-se específico, preciso, linear, exato e robusto podendo ser utilizado como alternativa ao método oficial preconizado pela Farmacopéia Americana em ensaios de controle de qualidade.Os resultados obtidos na avaliação do fármaco quando submetido a determinadas condições de estresse sugerem que o fármaco é susceptível à fotólise