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2.
Turk Psikiyatri Derg ; 30(2): 145-148, 2019.
Artigo em Turco | MEDLINE | ID: mdl-31487381

RESUMO

Bupropion is a selective norepinephrine and dopamine reuptakeinhibitor. It is used in the treatment of depression and nicotineaddiction. When compared to the other antidepressants, bupropion hasa relatively lower risk of triggering shift to hypomania or mania in bipolardepression treatment. Here we report two cases of bipolar depressionpatients with manic shift when bupropion was used as an adjunct tomood stabilizer treatment. The first was a 43-year old female patient.Manic symptoms occurred after bupropion was added to lithium andquetiapine treatment for bipolar disorder (BD) depressive episode.Her manic symptoms regressed rapidly after discontinuing bupropiontreatment. The second patient was a 26-year old male on lithium andvalproate therapy with a BD diagnosis. After bupropion was added tohis treatment for depressive symptoms, psychotic mania ensued and hehad to be admitted to the hospital. Significant improvement was notedshortly after bupropion was discontinued and antipsychotic treatmentwas initiated.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antipsicóticos/administração & dosagem , Transtorno Bipolar/psicologia , Bupropiona/efeitos adversos , Transtorno Depressivo/psicologia , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino
3.
Trials ; 20(1): 468, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362784

RESUMO

BACKGROUND: The purpose of this study was to compare the effect of 300 mg of bupropion and 8 mg of buprenorphine per day on the treatment of methamphetamine withdrawal cravings over a 2-week treatment interval. METHOD: Sixty-five methamphetamine-dependent men who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria for methamphetamine dependence and withdrawal were randomly divided into two groups. Subjects randomly received 300 mg of bupropion or 8 mg of buprenorphine per day in a psychiatric ward. Of the 65 subjects, 35 (53.8%) received buprenorphine and 30 (46.2%) received bupropion. The subjects were assessed by using methamphetamine craving score, interview, and negative urine drug test. FINDINGS: There were no statistically significant differences between the two groups in regard to age, education, duration of methamphetamine dependency, marital status, employment, and income. The mean ages were 32.8 years (standard deviation (SD) = 7.26, range = 22 to 59) for the buprenorphine group and 32.21 years (SD = 8.45, range = 17 to 51) for the bupropion group. All 65 patients completed the 2-week study. Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group (P = 0.011). Overall, a significant main effect of day (P <0.001) and group (P = 0.011) and a non-significant group-by-day interaction (P >0.05) were detected. CONCLUSIONS: The results support the safety and effectiveness of buprenorphine and bupropion in the treatment of methamphetamine withdrawal craving. Administration of 8 mg of buprenorphine per day can be recommended for the treatment of methamphetamine withdrawal cravings. We should note that it is to be expected that craving decreases over time without any medication. So the conclusion may not be that bupropion and buprenorphine both lower the craving. As the buprenorphine is superior to bupropion, only buprenorphine does so for sure. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) registration number: IRCT2015010320540N1 . Date registered: April 10, 2015.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Comportamento Aditivo/tratamento farmacológico , Buprenorfina/uso terapêutico , Bupropiona/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Fissura/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Metanfetamina/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Analgésicos Opioides/efeitos adversos , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/psicologia , Buprenorfina/efeitos adversos , Bupropiona/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
Drug Metab Rev ; 51(3): 293-313, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31124380

RESUMO

Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion reach higher plasma concentrations than bupropion. Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors. Recent reports highlight recreational use of bupropion via intranasal insufflation and intravenous use. Seizures, insomnia, agitation, headache, dry mouth, and nausea are some of the reported adverse effects. Neurologic effects are major signs of intoxication that should be carefully managed. Finally, the characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure, including the evaluation of potential drug-drug interactions and pharmacogenetic implications.


Assuntos
Bupropiona/farmacologia , Bupropiona/farmacocinética , Animais , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/química , Antidepressivos de Segunda Geração/farmacocinética , Antidepressivos de Segunda Geração/farmacologia , Bupropiona/efeitos adversos , Bupropiona/química , Toxicologia Forense , Humanos
6.
Cochrane Database Syst Rev ; 3: CD011268, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883669

RESUMO

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


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Diarreia/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Incidência , Náusea/induzido quimicamente , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Transtorno Afetivo Sazonal/epidemiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
7.
Andrologia ; 51(6): e13268, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30873645

RESUMO

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.


Assuntos
Antidepressivos/efeitos adversos , Bupropiona/efeitos adversos , Fertilidade/efeitos dos fármacos , Paroxetina/efeitos adversos , Maturidade Sexual/efeitos dos fármacos , Adolescente , Animais , Humanos , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Fatores de Tempo
8.
J Clin Psychopharmacol ; 39(2): 108-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30811371

RESUMO

BACKGROUND: Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest. METHODS: We performed secondary analyses of safety and efficacy outcomes by psychiatric diagnosis in EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), a 12-week, randomized, double-blind, triple-dummy, placebo- and active (NRT)-controlled trial of varenicline and bupropion with 12-week follow-up, in a subset population, n = 4092, with a primary psychotic (n = 390), anxiety (n = 792), or mood (n = 2910) disorder. Primary end-point parameters were incidence of prespecified moderate and severe neuropsychiatric adverse events (NPSAEs) and weeks 9 to 12 continuous abstinence rates (9-12CAR). RESULTS: The observed NPSAE incidence across treatments was 5.1% to 6.3% in those with a psychotic disorder, 4.6% to 8.0% in those with an anxiety disorder, and 4.6% to 6.8% in those with a mood disorder. Neither varenicline nor bupropion was associated with significantly increased NPSAEs relative to NRT or placebo in the psychiatric cohort or any psychiatric diagnostic subcohort. There was a significant effect of treatment on 9-12CAR (P < 0.0001) and no significant treatment-by-diagnostic subcohort interaction (P = 0.24). Abstinence rates with varenicline were superior to bupropion, NRT, and placebo, and abstinence with bupropion and NRT was superior to placebo. Within-diagnostic subcohort comparisons of treatment efficacy yielded estimated odds ratios for 9-12CAR versus placebo of greater than 3.00 for varenicline, greater than 1.90 for bupropion, and greater than 1.80 for NRT for all diagnostic groups. CONCLUSIONS: Varenicline, bupropion, and nicotine patch are well tolerated and effective in adults with psychotic, anxiety, and mood disorders. The relative effectiveness of varenicline, bupropion, and NRT versus placebo did not vary across psychiatric diagnoses.


Assuntos
Bupropiona/administração & dosagem , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco , Vareniclina/administração & dosagem , Adulto , Transtornos de Ansiedade/complicações , Bupropiona/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos Psicóticos/complicações , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Resultado do Tratamento , Vareniclina/efeitos adversos
9.
Clin Neuropharmacol ; 42(1): 19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30499776

RESUMO

Bupropion is antidepressant and a smoking cessation aid medication related to dopaminergic activity. We report for the first time a case of an older adult with a known tic disorder, which was in remission but exacerbated during treatment with bupropion. It has been reported that other dopaminergic compounds such as methylphenidate can exacerbate tic disorder. Clinicians should be aware of this potential adverse effect when prescribing bupropion to adults with tic and other motor disorders.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Transtornos de Tique/induzido quimicamente , Idoso , Antidepressivos de Segunda Geração/administração & dosagem , Bupropiona/administração & dosagem , Preparações de Ação Retardada , Humanos , Masculino
10.
Eur J Drug Metab Pharmacokinet ; 44(3): 339-352, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30520001

RESUMO

BACKGROUND AND OBJECTIVE: Bupropion is used for the treatment of major depressive disorder. We determined the pharmacokinetics, safety, and tolerability of extended-release bupropion XL in healthy Chinese volunteers. METHODS: This open-label, single-center pharmacokinetic study was conducted between May 2016 and June 2016. Eligible volunteers received bupropion XL 150 mg once daily for 5 days, then 300 mg once daily from days 6 to 14. Pharmacokinetic parameters were evaluated after first and repeated doses by non-compartmental and population pharmacokinetic analyses. RESULTS: Fifteen out of 16 enrolled volunteers completed the study. The geometric mean of the bupropion area under the concentration-time curve from 0 to 24 h (AUC0-24) was 498.2 and 1,165.7 h·ng/mL on days 1 and 14, respectively; maximum plasma concentration (Cmax) was 49.9 ng/mL on day 1 and steady-state maximum observed plasma concentration (Css_max) was 111.9 ng/mL on day 14. Among the three metabolites, hydroxybupropion showed the highest AUC0-24 and Cmax. The population pharmacokinetic model findings indicated an apparent oral clearance of 221 L/h for bupropion in a typical healthy 60.9-kg Chinese volunteer. CONCLUSIONS: This was the first pharmacokinetic study for bupropion XL and its active metabolites in the Chinese population. The AUC and Cmax of bupropion XL and its three metabolites increased approximately in a dose-proportional manner with an increase from 150 mg to 300 mg. Adverse events were similar to those reported in studies outside China. A population pharmacokinetic model was developed for bupropion XL, with pharmacokinetics of bupropion adequately described by a two-compartment model with first-order absorption and linear elimination plus lag time. TRIAL REGISTRATION NUMBER: NCT02698553.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacocinética , Bupropiona/efeitos adversos , Bupropiona/farmacocinética , Modelos Biológicos , Administração Oral , Adulto , Antidepressivos de Segunda Geração/administração & dosagem , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Bupropiona/administração & dosagem , China , Preparações de Ação Retardada , Transtorno Depressivo Maior/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino
11.
Ann Pharmacother ; 53(2): 186-194, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30081645

RESUMO

OBJECTIVE: This nonsystematic review describes risk of bleeding in treatment with serotonin reuptake inhibitors (SRIs) and provide recommendations for the management of patients at risk of bleeding. DATA SOURCES: Articles were identified by English-language MEDLINE search published prior to June 2018 using the terms SRI, serotonin and noradrenaline reuptake inhibitors, OR antidepressive agents, AND hemorrhage OR stroke. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses were utilized to identify information regarding risk of bleeding with antidepressants. Individual studies were included if they had information regarding bleeding risk with specific SRIs, timing of risk, or risk with medications of interest. DATA SYNTHESIS: SRIs increase risk of bleeding by 1.16- to 2.36-fold. The risk is synergistic between SRIs and nonsteroidal anti-inflammatory drugs (NSAIDs; odds ratio [OR] range between studies 3.17-10.9). Acid-reducing medications may mitigate risk of gastrointestinal bleeds in chronic NSAIDs and SRI users (OR range between studies 0.98-1.1). Antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be appropriate alternatives for patients at risk of bleeding. Relevance to Patient Care and Clinical Practice: This review includes data regarding bleeding risk for specific antidepressants, concomitant medications, and risk related to duration of SRI use. Considerations and evidence-based recommendations are provided for management of SRI users at high bleeding risk. CONCLUSIONS: Clinicians must be aware of the risk of bleeding with SRI use, especially for patients taking NSAIDs. Patient education is prudent for those prescribed NSAIDs and SRIs concurrently.


Assuntos
Antidepressivos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/terapia , Inibidores de Captação de Serotonina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Antidepressivos/administração & dosagem , Bupropiona/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Hemorragia/epidemiologia , Humanos , Mirtazapina/efeitos adversos , Fatores de Risco , Inibidores de Captação de Serotonina/administração & dosagem
12.
Clin Pharmacol Ther ; 105(5): 1164-1174, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30460996

RESUMO

Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double-blinded crossover in 70 adults with major depression in stable remission taking any bupropion XL 300 mg tested bioequivalence and therapeutic equivalence of available XL 300 mg products. After a 4-week lead-in on patients' existing bupropion, four 6-week phases evaluated brand and three generics. Patients were uninformed of switching. Drug overencapsulation ensured blinding. There were no differences between any generic and brand, or between generics, in peak plasma concentration (Cmax ) and area under the plasma concentration-time curve over the 24-hour dosing interval (AUC0-24 ) for racemic bupropion or major metabolites. All generics met formal bioequivalence criteria for bupropion and metabolites. There were no differences between generics and brand, or between generics, in depression symptoms or side effects, assessed by every 3-week in-person interview and daily smartphone-based self-report. There were no differences in patients' perceptions of bupropion products. Results show three bupropion XL 300 mg generic products are both bioequivalent and not therapeutically different from brand drug and each other.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Medicamentos Genéricos/uso terapêutico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacocinética , Bupropiona/efeitos adversos , Bupropiona/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Medicamentos Genéricos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Equivalência Terapêutica , Resultado do Tratamento
13.
Pharmacopsychiatry ; 52(3): 134-141, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29660754

RESUMO

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


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/induzido quimicamente , Masculino , Programas Nacionais de Saúde/estatística & dados numéricos , Prescrições/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
14.
J Clin Pharm Ther ; 44(2): 174-179, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30578565

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Pharmacogenomics holds promise in smoking cessation because of its potential to shed light on the complexity of drug metabolism and improve treatments using therapeutic agents. The cytochrome P450 2B6 gene (CYP2B6) encodes CYP2B6 enzyme that has been found to mediate the hydroxylation of bupropion, a smoking cessation aid. CYP2B6 exhibits a range of polymorphic variants that alter the pharmacokinetics and pharmacodynamics of bupropion. Genetic variations in CYP2B6 may influence the risk of adverse effects or efficacy of treatment with bupropion. The objective of this review was to investigate the influence of pharmacogenomics on smoking cessation therapy. METHODS: A thorough literature search was conducted on PubMed, SCOPUS and EMBASE using keywords related to bupropion, smoking cessation, pharmacogenomics and CYP2B6. Research and review articles, case reports and clinical and preclinical studies pertinent to the research topic were identified, evaluated and summarized. Cited articles within the above-mentioned sources also provided pertinent information. RESULTS: There is strong literature evidence to prove that CYP2B6 polymorphisms affect pharmacokinetic and pharmacodynamic properties of bupropion, thus affecting the therapeutic outcome of smoking cessation therapy. WHAT IS NEW AND CONCLUSIONS: Complete understanding of pharmacogenetic variation of bupropion pharmacokinetics and pharmacodynamics will be beneficial for designing safer and more personalized smoking cessation therapy with improved outcomes.


Assuntos
Bupropiona/administração & dosagem , Citocromo P-450 CYP2B6/genética , Abandono do Hábito de Fumar/métodos , Bupropiona/efeitos adversos , Bupropiona/farmacocinética , Variação Genética , Humanos , Farmacogenética , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Agentes de Cessação do Hábito de Fumar/farmacocinética
15.
Pharm Res ; 36(1): 1, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30402714

RESUMO

PURPOSE: A three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition. METHODS: Monkeys were administered either an i.v. infusion (0.1 mg/kg) or an oral dose of digoxin (0.2 mg/kg) as control. In single-dosing period, monkeys received an i.v. infusion of bupropion at 1.5 mg/kg together with an infusion or oral dosing of digoxin, respectively. During multiple-dosing period, bupropion was orally administered q.d. at 7.72 mg/kg for 12-day. Then it was co-administered with an i.v. infusion or oral dosing of digoxin, respectively. Renal expression of OATP4C1 and P-gp was examined. RESULTS: Bupropion significantly increased i.v. digoxin CLrenal0-48h by 1 fold in single-dosing period. But it had no effect on the systemic disposition of digoxin. In multiple-dosing period, bupropion significantly increased oral digoxin CLrenal0-48h, CLtotal0-48h, CLnon-renal0-48h and decreased its plasma exposure. Bupropion and its metabolites did not alter creatinine clearance. OATP4C1 was located at the basolateral membrane of proximal tubule cells, while P-gp was on the apical membrane. CONCLUSIONS: The effect of multiple dosing with bupropion on the pharmacokinetics of digoxin is more pronounced. The magnitude of increase in digoxin CLrenal0-48h contributed to the decrease in AUC of digoxin in some extent, but certainly is not the major driving force. The lack of systemic exposure after a single dose but a significant decrease in exposure mediated by an increase in the digoxin CLnon-renal0-48h with repeated dosing is likely to be the more clinically relevant.


Assuntos
Bupropiona/farmacocinética , Digoxina/farmacocinética , Administração Oral , Animais , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Digoxina/administração & dosagem , Digoxina/efeitos adversos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Macaca fascicularis , Metaboloma , Metabolômica , Distribuição Tecidual
16.
Rev Med Chil ; 146(5): 665-669, 2018 May.
Artigo em Espanhol | MEDLINE | ID: mdl-30148931

RESUMO

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.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Coma/induzido quimicamente , Overdose de Drogas/complicações , Hipóxia Encefálica/induzido quimicamente , Transtornos da Motilidade Ocular/induzido quimicamente , Idoso , Evolução Fatal , Feminino , Humanos , Imagem por Ressonância Magnética , Transtornos da Personalidade/tratamento farmacológico , Suicídio
17.
Am J Mens Health ; 12(5): 1705-1718, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29973132

RESUMO

Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of "much/very much improved" (CGI-SF score = 2) was reported by 58.3% ( n = 21/36) of bupropion SR-assigned versus 27.7% ( n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.


Assuntos
Bupropiona/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Metadona/efeitos adversos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Adulto , Bupropiona/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Disfunção Erétil/induzido quimicamente , Humanos , Masculino , Metadona/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Resultado do Tratamento
18.
Clin Toxicol (Phila) ; 56(12): 1179-1184, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29989445

RESUMO

BACKGROUND: Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants. METHODS: We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index. RESULTS: We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk. CONCLUSIONS: The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.


Assuntos
Idoso/estatística & dados numéricos , Antidepressivos de Segunda Geração/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Idoso de 80 Anos ou mais , Bupropiona/efeitos adversos , Estudos de Casos e Controles , Citalopram/efeitos adversos , Cloridrato de Duloxetina/efeitos adversos , Feminino , Fluvoxamina/efeitos adversos , Humanos , Masculino , Razão de Chances , Ontário/epidemiologia , População
19.
J Clin Psychopharmacol ; 38(4): 349-356, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901567

RESUMO

BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.


Assuntos
Antidepressivos/efeitos adversos , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/epidemiologia , Bupropiona/efeitos adversos , Estudos de Casos e Controles , Citalopram/efeitos adversos , Cloridrato de Duloxetina/efeitos adversos , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Mianserina/efeitos adversos , Mianserina/análogos & derivados , Pessoa de Meia-Idade , Mirtazapina , Paroxetina/efeitos adversos , Farmacoepidemiologia , Sertralina/efeitos adversos , Estados Unidos/epidemiologia , Cloridrato de Venlafaxina/efeitos adversos
20.
Artigo em Inglês | MEDLINE | ID: mdl-29873957

RESUMO

Objective: Use of second-generation antipsychotics (SGAs) for treatment of depression has increased, and patients with depression and comorbid diabetes or cardiovascular disease are more likely to use SGAs than those without these conditions. We compared SGA and non-SGA depression pharmacotherapies on the risk of diabetes hospitalization or treatment intensification in adults with depression and preexisting diabetes. Methods: This was a retrospective cohort study of US commercially insured adults (2009-2015 Truven MarketScan Commercial Claims and Encounters Database) aged 18-64 years old with type 2 diabetes mellitus and unipolar depression previously treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. New users of SGAs versus non-SGAs, as well as specific treatments (aripiprazole, quetiapine, bupropion, mirtazapine, and tricyclic antidepressants [TCAs]) were matched on class/medication-specific high-dimensional propensity score. Cox proportional hazard models were used to compare the risk of diabetes-related hospitalization or treatment intensification. Results: We identified 6,625 SGA (aripiprazole = 3,461; quetiapine = 1,977; other = 1,187) and 23,921 non-SGA patients for inclusion (bupropion = 15,511; mirtazapine = 1,837; TCAs = 5,989; other = 584) with a mean age of 51 years. In the matched cohort, the rate of diabetes-related hospitalization or drug intensification was 47.9 per 100 person-years in the SGA group and 43.5 per 100 person-years in the non-SGA group (adjusted hazard ratio [aHR] = 1.03; 95% CI, 0.96-1.11). When comparing treatment subgroups, the risk of events was lower for bupropion versus TCAs (aHR = 0.85; 95% CI, 0.76-0.98), quetiapine versus mirtazapine (aHR = 0.82; 95% CI, 0.67-0.99), and quetiapine versus TCAs (aHR = 0.84; 95% CI, 0.72-0.98). For other comparisons, differences were small and not statistically significant. Conclusions: While drug-specific effects on risk of diabetes hospitalization or treatment intensification most likely guide clinical decision making, we observed only modest differences in risk. The overall impact of SGAs on diabetes control depends not only on direct effects on glucose metabolism but also on effectiveness of depression symptom relief. Future studies evaluating other diabetes outcomes (glycosylated hemoglobin, diabetes complications) are needed.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Depressivo/tratamento farmacológico , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Bupropiona/efeitos adversos , Comorbidade , Transtorno Depressivo/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Mianserina/efeitos adversos , Mianserina/análogos & derivados , Pessoa de Meia-Idade , Mirtazapina , Modelos de Riscos Proporcionais , Fumarato de Quetiapina/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
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