RESUMO
PURPOSE: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.
Assuntos
Neoplasias da Mama/terapia , Bupropiona/administração & dosagem , Sobreviventes de Câncer/psicologia , Inibidores da Captação de Dopamina/administração & dosagem , Neoplasias dos Genitais Femininos/terapia , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Adulto , Idoso , Bupropiona/efeitos adversos , Preparações de Ação Retardada , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Pós-Menopausa , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/psicologia , Fatores de Tempo , Resultado do Tratamento , Estados UnidosAssuntos
Bupropiona/efeitos adversos , Inibidores da Colinesterase/efeitos adversos , Demência Vascular/tratamento farmacológico , Demência Vascular/fisiopatologia , Donepezila/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Comportamento Sexual/efeitos dos fármacos , Idoso , Quimioterapia Combinada , HumanosAssuntos
Encéfalo/diagnóstico por imagem , Cocaína/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Adulto , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Imageamento por Ressonância Magnética , MasculinoRESUMO
Evidence linking cocaine to the risk of pulmonary hypertension (PH) is limited and inconsistent. We examined whether cocaine use, in the absence of other known causes of PH, was associated with elevated systolic pulmonary artery pressure (sPAP) and increased probability of PH. We compared patients with documented cocaine use to a randomly selected age, sex, and race-matched control group without history of cocaine use. All participants had no known causes of PH and underwent echocardiography for noninvasive estimation of sPAP. We used routinely reported echocardiographic parameters and contemporary guidelines to grade the probability of PH. In 88 patients with documented cocaine use (mean age ± standard deviation 51.7 ± 9.5 years), 33% were women and 89% were of Black race. The commonest route of cocaine use was smoking (74%). Cocaine users compared with the control group had significantly higher sPAP (mean ± standard deviation, 30.1 ± 13.1 vs 22.0 ± 9.8 mm Hg, p <0.001) and greater likelihood of PH (25% vs 10%, pâ¯=â¯0.012). In multivariable analyses adjusted for potential confounders including left ventricular diastolic dysfunction, cocaine use conferred a fivefold greater odds of echocardiographic PH (pâ¯=â¯0.006). Additionally, a stepwise increase in the likelihood of PH was noted across cocaine users with negative or no drug screen on the day of echocardiography to cocaine users with a positive drug screen (multivariable p for trendâ¯=â¯0.008). In conclusion, cocaine use was associated with a higher sPAP and an increased likelihood of echocardiographic PH with a probable acute-on-chronic effect.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína/efeitos adversos , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Artéria Pulmonar/diagnóstico por imagem , Pressão Propulsora Pulmonar/efeitos dos fármacos , Cateterismo Cardíaco , Inibidores da Captação de Dopamina/efeitos adversos , Feminino , Seguimentos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SístoleAssuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Bupropiona/efeitos adversos , Clonidina/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores da Captação de Dopamina/efeitos adversos , Sonhos/efeitos dos fármacos , Sono REM/efeitos dos fármacos , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Clonidina/administração & dosagem , Feminino , HumanosRESUMO
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 JovemRESUMO
RATIONALE: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI). OBJECTIVES: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse. METHODS: rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10â¯mg/kg) or bupropion (20â¯mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems. RESULTS: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems. CONCLUSIONS: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.
Assuntos
Alcoolismo/tratamento farmacológico , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/uso terapêutico , Consumo de Bebidas Alcoólicas , Alcoolismo/psicologia , Animais , Endocanabinoides/metabolismo , Fluoxetina/uso terapêutico , Masculino , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores de Glutamato/biossíntese , Receptores de Glutamato/genética , Recidiva , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
BACKGROUND: The consequences of cocaine use are multisystemic, such as, for instance, renal failure, hepatotoxicity and pulmonary toxicity, with renal alterations being the focus of the present study. The use of substances that modify the base composition of cocaine (or adulterants) aiming to potentiate its effects also has an impact on these manifestations. The present study aims to report three cases with different diagnosis of acute kidney injury related to cocaine use. CASE PRESENTATION: Case 01 - A 30-year-old female patient, who regularly used cocaine, started to have lower-limb edema, which showed a progressive and ascending evolution, affecting the face a few days later, associated with an isolated febrile episode and oligoanuria. The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) was verified: reactive 1:80, with renal biopsy compatible with rapidly progressive glomerulonephritis (RPGN). Case 02 - A 34-year-old female patient, with difficult-to-control hypertension and a frequent user of cocaine, showed generalized sudden edema together with diffuse and progressive pruritus associated with oliguria, fever, nausea, and vomiting. Schistocyte screening was positive, with negative direct Coombs test, and negative serologies for hepatitis B, C and HIV, as well as negative anti-double-stranded DNA, Anti-SSA and Anti-SSB. The renal biopsy was compatible with thrombotic microangiopathy, associated with moderate interstitial fibrosis and acute tubular necrosis Case 03 - A 25-year-old male patient who had been a cocaine user for 5 years had a sudden onset of generalized disabling myalgia (especially in the lower limbs) associated with recent frontotemporal headache, palpitation, dizziness, and a non-measured febrile episode; the patient had used cocaine at the night before symptom onset. CPK was 1731 U/L.The final probable diagnosis was AKI secondary to cocaine-induced rhabdomyolysis. CONCLUSIONS: In conclusion basically, 05 etiologies of acute kidney injury should always be remembered: rhabdomyolysis, thrombotic microangiopathy, vasculitis, acute interstitial nephritis and renal infarction. Emphasis should be given to rhabdomyolysis due to its higher prevalence. Considering the increasing rates of cocaine use, especially with the use of adulterating substances, these pathologies will likely be increasingly prevalent.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Cocaína/efeitos adversos , Vasoconstritores/efeitos adversos , Injúria Renal Aguda/sangue , Adulto , Transtornos Relacionados ao Uso de Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/complicações , Inibidores da Captação de Dopamina/efeitos adversos , Feminino , Humanos , MasculinoRESUMO
BACKGROUND Serotonin syndrome is a condition characterized predominantly by neuromuscular symptoms and altered thermoregulation in response to serotonergic overtone. Treatment is focused on withdrawal of serotonergic agents, which leads to resolution in the majority of cases. In the setting of serotonergic overdose, the onset of serotonin syndrome is usually within 4 to 13 h. Here, we report a case of delayed-onset serotonin syndrome in a patient who ingested a mixture of longer-acting serotonin agonists with serotonin antagonists. CASE REPORT A 24-year-old male was transferred to our medical intensive care unit with hypotension and altered mental status after an overdose of fluoxetine, cyproheptadine, trazodone, olanzapine, risperidone, and bupropion. After approximately 72 h, the patient developed symptoms of fever, lower leg clonus, hyperreflexia, and agitation. He was diagnosed with delayed-onset serotonin syndrome, which responded well to re-administration of cyproheptadine, leading to resolution of symptoms by day 5 of his stay. CONCLUSIONS In this present case, our patient presented with the longest reported delay in the onset of serotonin syndrome after intentional ingestion. This was likely secondary to co-ingestion of long-acting serotonin agonists with protective shorter-acting serotonin antagonists (cyproheptadine and olanzapine). Clinicians should consider delayed-onset serotonin syndrome when patients ingest longer-acting serotonergic agents with serotonin antagonists.
Assuntos
Overdose de Drogas/tratamento farmacológico , Fluoxetina/efeitos adversos , Serotoninérgicos/efeitos adversos , Serotoninérgicos/uso terapêutico , Síndrome da Serotonina/induzido quimicamente , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Ciproeptadina/administração & dosagem , Ciproeptadina/efeitos adversos , Ciproeptadina/uso terapêutico , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/efeitos adversos , Overdose de Drogas/complicações , Fluoxetina/administração & dosagem , Humanos , Masculino , Olanzapina , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Serotoninérgicos/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/efeitos adversos , Síndrome da Serotonina/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Fatores de Tempo , Trazodona/administração & dosagem , Trazodona/efeitos adversos , Adulto JovemAssuntos
Bupropiona/efeitos adversos , Dopaminérgicos/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Memantina/efeitos adversos , Mioclonia/etiologia , Náusea/induzido quimicamente , Náusea/complicações , Vômito/induzido quimicamente , Vômito/complicações , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Feminino , Humanos , Doença de Parkinson/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate data on birth outcomes following bupropion use during pregnancy. DATA SOURCES: A systematic literature review of PubMed and PsycINFO was performed through June 2017 for clinical studies published in English. The following keywords were used: bupropion, pregnancy, depression, smoking cessation, birth outcomes, miscarriage, and spontaneous abortion. References and related articles were also searched to yield additional publications. With the exception of limiting the search to human subjects, no other limitations were applied in an effort to capture all relevant published studies. STUDY SELECTION/DATA EXTRACTION: No studies were excluded. A total of 8 studies were included in this review. RESULTS: Bupropion's use in the first trimester has been linked with a small elevation in the risk of cardiovascular defects, although the absolute risk was low and confounding by indication (eg, use for smoking cessation) cannot be excluded. While the risk of miscarriage following prenatal bupropion exposure was higher than that of a control group of women in one study, it remained within the general population rate. CONCLUSIONS: While more studies are needed, research to date suggests that bupropion may be a reasonable treatment option for depressed pregnant women who require pharmacotherapy, particularly when they also are attempting to reduce nicotine use during pregnancy.
Assuntos
Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Abandono do Hábito de Fumar , Aborto Espontâneo/epidemiologia , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD. OBJECTIVE: To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD. METHODS: In a retrospective cohort study, we used data from 14â 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10â 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6â months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders. RESULTS: Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely. CONCLUSION: In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT.
Assuntos
Bupropiona/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Inibidores da Captação de Dopamina/efeitos adversos , Transtornos Mentais/epidemiologia , Agonistas Nicotínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Vareniclina/efeitos adversos , Adulto , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Methods: Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Results: Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. Conclusions: These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients.
Assuntos
Bupropiona/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Afeto/efeitos dos fármacos , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Anedonia/efeitos dos fármacos , Mapeamento Encefálico , Bupropiona/efeitos adversos , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Estudos Cross-Over , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Oxigênio/sangue , Córtex Pré-Frontal/diagnóstico por imagem , Descanso , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to compare the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder (MDD) unresponsive to selective serotonin reuptake inhibitors (SSRIs). METHODS: This is the first randomized, prospective, open-label, direct comparison study between aripiprazole and bupropion augmentation. Participants had at least moderately severe depressive symptoms after 4 weeks or more of SSRI treatment. A total of 103 patients were randomized to either aripiprazole (n = 56) or bupropion (n = 47) augmentation for 6 weeks. Concomitant use of psychotropic agents was prohibited. Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores were obtained at baseline and after 1, 2, 4, and 6 weeks of treatment. RESULTS: Overall, both treatments significantly improved depressive symptoms without causing serious adverse events. There were no significant differences in the Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, and Iowa Fatigue Scale scores, and response rates. However, significant differences in remission rates between the 2 groups were evident at week 6 (55.4% vs 34.0%, respectively; P = 0.031), favoring aripiprazole over bupropion. There were no significant differences in adverse sexual events, extrapyramidal symptoms, or akathisia between the 2 groups. CONCLUSIONS: The present study suggests that aripiprazole augmentation is at least comparable to bupropion augmentation in combination with SSRI in terms of efficacy and tolerability in patients with MDD. Both aripiprazole and bupropion could help reduce sexual dysfunction and fatigue in patients with MDD. Aripiprazole and bupropion may offer effective and safe augmentation strategies in patients with MDD who are unresponsive to SSRIs. Double-blinded trials are warranted to confirm the present findings.
Assuntos
Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Bupropiona/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Inibidores da Captação de Dopamina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Aripiprazol/efeitos adversos , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/efeitos adversos , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Metilfenidato/uso terapêutico , Farmacogenética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Inibidores da Captação de Dopamina/efeitos adversos , Dopamina beta-Hidroxilase/genética , Feminino , Frequência do Gene , Interação Gene-Ambiente , Haplótipos , Humanos , Metilfenidato/efeitos adversos , Razão de Chances , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética , Fatores de Risco , Fumar/efeitos adversos , Resultado do Tratamento , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse.
Assuntos
Tonsila do Cerebelo/metabolismo , Analgésicos Opioides/efeitos adversos , Comportamento Animal , Agonistas de Receptores de Canabinoides/efeitos adversos , Depressores do Sistema Nervoso Central/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Comportamento Social , Síndrome de Abstinência a Substâncias/fisiopatologia , Abstinência de Álcool , Animais , Ansiedade/psicologia , Encéfalo/metabolismo , Cocaína/efeitos adversos , Dronabinol/efeitos adversos , Comportamento de Procura de Droga , Emoções , Etanol/efeitos adversos , Masculino , Camundongos , Morfina/efeitos adversos , Motivação , Nicotina/efeitos adversos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Comportamento Estereotipado/fisiologia , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologiaRESUMO
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders of childhood and adolescence. Stimulants are usually the first choice of drug; however, as many as 20% of patients do not respond to them. Stimulants may also worsen comorbid sleep, mood, and anxiety disorders, and they are associated with problems of misuse and diversion. Bupropion, a dopamine and norepinephrine reuptake inhibitor, is a promising nonstimulant alternative with reports of positive outcomes for ADHD management in both adolescent and adult populations. This study systematically reviews clinical trials on the subject. METHODS: Using the keywords bupropion or Wellbutrin or Zyban or Elontril and attention deficit hyperactivity disorder or ADHD or ADDH, a preliminary search on the PubMed and Ovid databases yielded 25,455 articles published in English between January 1, 1988 and May 1, 2016. Of these, there were only six articles on clinical trials involving children. Full articles were also reviewed for references of interest. RESULTS: All available open, controlled, and randomized trials demonstrated bupropion's efficacy in improving ADHD symptoms. The three head-to-head trials found that bupropion had efficacy comparable to methylphenidate (p > 0.05). However, a large double-blind, placebo-controlled multicenter study of bupropion found smaller effect sizes for bupropion, as quantified using teacher and parent ratings of ADHD symptoms, than methylphenidate. In terms of tolerability, a head-to-head trial found that headache was observed more frequently in the methylphenidate-treated group than in the bupropion-treated group, whereas the frequency of other side effects did not differ significantly. CONCLUSION: Current findings should be interpreted with caution because of the very limited database. Bupropion should be considered for pharmacological management of childhood and adolescent ADHD, but more randomized controlled trials with larger sample sizes are warranted. There is also some evidence of its benefits in children with comorbid ADHD and conduct, substance use, or depressive disorders.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Bupropiona/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Bupropiona/efeitos adversos , Bupropiona/farmacologia , Criança , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/farmacologia , Humanos , Metilfenidato/efeitos adversos , Metilfenidato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: This 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder. METHODS: The study was conducted in 2 stages of recruitment across 3 sites; 20 participants were enrolled in stage 1 and 29 participants were enrolled in stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol) plus extended-release oral bupropion (BRP; Wellbutrin XL) were provided with a smartphone-assisted medication adherence platform. Participants met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for severe MA use disorder, self-reported ≥20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in week 9. RESULTS: Analyses evaluated effects of XR-NTXâ+âBRP to determine the number of "responders" according to a statistically predefined response criterion (6 of 8 MA-negative UDS during the last 4 weeks of medication). The 2-stage design required that stage 1 yield ≥3 responders to continue to stage 2; 11 of the 49 participants met responder criteria across both stages (5 in stage 1, 6 in stage 2). CONCLUSIONS: Under the statistical analysis plan, study "success" required ≥9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Bupropiona/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Metanfetamina/efeitos adversos , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Preparações de Ação Retardada , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos , Projetos Piloto , Adulto JovemRESUMO
BACKGROUND: Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion. Their efficacy relative to nicotine patch largely relies on indirect comparisons, and there is limited information on safety and efficacy in smokers with psychiatric disorders. We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders. METHODS: We did a randomised, double-blind, triple-dummy, placebo-controlled and active-controlled (nicotine patch; 21 mg per day with taper) trial of varenicline (1 mg twice a day) and bupropion (150 mg twice a day) for 12 weeks with 12-week non-treatment follow-up done at 140 centres (clinical trial centres, academic centres, and outpatient clinics) in 16 countries between Nov 30, 2011, and Jan 13, 2015. Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit. Randomisation was computer generated (1:1:1:1 ratio). Participants, investigators, and research personnel were masked to treatment assignments. The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events. The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9-12. All participants randomly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis. The trial is registered at ClinicalTrials.gov (number NCT01456936) and is now closed. FINDINGS: 8144 participants were randomly assigned, 4116 to the psychiatric cohort (4074 included in the safety analysis) and 4028 to the non-psychiatric cohort (3984 included in the safety analysis). In the non-psychiatric cohort, 13 (1·3%) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group, 22 (2·2%) of 989 in the bupropion group, 25 (2·5%) of 1006 in the nicotine patch group, and 24 (2·4%) of 999 in the placebo group. The varenicline-placebo and bupropion-placebo risk differences (RDs) for moderate and severe neuropsychiatric adverse events were -1·28 (95% CI -2·40 to -0·15) and -0·08 (-1·37 to 1·21), respectively; the RDs for comparisons with nicotine patch were -1·07 (-2·21 to 0·08) and 0·13 (-1·19 to 1·45), respectively. In the psychiatric cohort, moderate and severe neuropsychiatric adverse events were reported in 67 (6·5%) of 1026 participants in the varenicline group, 68 (6·7%) of 1017 in the bupropion group, 53 (5·2%) of 1016 in the nicotine patch group, and 50 (4·9%) of 1015 in the placebo group. The varenicline-placebo and bupropion-placebo RDs were 1·59 (95% CI -0·42 to 3·59) and 1·78 (-0·24 to 3·81), respectively; the RDs versus nicotine patch were 1·22 (-0·81 to 3·25) and 1·42 (-0·63 to 3·46), respectively. Varenicline-treated participants achieved higher abstinence rates than those on placebo (odds ratio [OR] 3·61, 95% CI 3·07 to 4·24), nicotine patch (1·68, 1·46 to 1·93), and bupropion (1·75, 1·52 to 2·01). Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo (OR 2·07 [1·75 to 2·45] and 2·15 [1·82 to 2·54], respectively). Across cohorts, the most frequent adverse events by treatment group were nausea (varenicline, 25% [511 of 2016 participants]), insomnia (bupropion, 12% [245 of 2006 participants]), abnormal dreams (nicotine patch, 12% [251 of 2022 participants]), and headache (placebo, 10% [199 of 2014 participants]). Efficacy treatment comparison did not differ by cohort. INTERPRETATION: The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo. Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence, whereas bupropion and nicotine patch were more effective than placebo. FUNDING: Pfizer and GlaxoSmithKline.