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1.
Rev Med Liege ; 75(11): 754-758, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33155451

RESUMO

The article describes a clinical case of catatonic syndrome. We describe the manifestations of the syndrome, its diagnostic criteria and associated scales. The modalities of the challenge test, constituting a diagnostic test, and first line treatment are detailed. Clinical and paraclinical investigations are proposed to determine the etiology. The benzodiazepine withdrawal as an etiology of catatonic syndrome is detailed.


Assuntos
Catatonia , Síndrome de Abstinência a Substâncias , Benzodiazepinas/efeitos adversos , Catatonia/induzido quimicamente , Catatonia/diagnóstico , Catatonia/tratamento farmacológico , Humanos , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/etiologia
2.
Yakugaku Zasshi ; 140(10): 1199-1206, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999198

RESUMO

Potential risks to the fetus or infant should be considered prior to medication during pregnancy and lactation. It is essential to evaluate the exposure levels of drugs and their related factors in addition to toxicological effects. Epilepsy is one of the most common neurological complications in pregnancy; some women continue to use antiepileptic drugs (AEDs) to control seizures. Benzodiazepines (BZDs) are widely prescribed for several women who experience symptoms such as anxiety and insomnia during the postpartum period. In this review, we describe the 1) transport mechanisms of AEDs across the placenta and the effects of these drugs on placental transporters, and 2) the transfer of BZDs into breast milk. Our findings indicated that carrier systems were involved in the uptake of gabapentin (GBP) and lamotrigine (LTG) in placental trophoblast cell lines. SLC7A5 was the main contributor to GBP transport in placental cells. LTG was transported by a carrier that was sensitive to chloroquine, imipramine, quinidine, and verapamil. Short-term exposure to 16 AEDs had no effect on folic acid uptake in placental cells. However, long-term exposure to valproic acid (VPA) affected the expression of folate carriers (FOLR1, SLC46A1). Furthermore, VPA administration changed the expression levels of various transporters in rat placenta, suggesting that sensitivity to VPA differed across gestational stages. Lastly, we developed a method for quantifying eight BZDs in human breast milk and plasma using LC/MS/MS, and successfully applied it to quantify alprazolam in breast milk and plasma donated by a lactating woman.


Assuntos
Anticonvulsivantes/metabolismo , Benzodiazepinas/metabolismo , Transporte Biológico/genética , Aleitamento Materno , Gabapentina/metabolismo , Lactação/metabolismo , Lamotrigina/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/fisiologia , Troca Materno-Fetal , Leite Humano/metabolismo , Placenta/metabolismo , Ácido Valproico/metabolismo , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Linhagem Celular , Epilepsia/tratamento farmacológico , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Gabapentina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Humanos , Lamotrigina/efeitos adversos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Transportador de Folato Acoplado a Próton/genética , Transportador de Folato Acoplado a Próton/metabolismo , Ácido Valproico/efeitos adversos
3.
JAMA Netw Open ; 3(10): e2019029, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33119104

RESUMO

Importance: The proportion of patients who develop long-term benzodiazepine use remains controversial, as do the length of time before long-term use develops and the factors associated with long-term use. Objective: To investigate the incidence of long-term benzodiazepine and related drug (BZDR) use and factors associated with the development of long-term use implementing a follow-up design with new BZDR users. Design, Setting, and Participants: This population-based cohort study used a nationwide cohort of 129 732 new BZDR users in Finland. New users of BZDRs aged 18 years or older were identified from the prescription register maintained by the Social Insurance Institution of Finland as individuals who initiated BZDR use during 2006 and had not used BZDRs from 2004 to 2005. The follow-up continued until death, long-term hospitalization, a gap of 2 years in BZDR use, or December 31, 2015. The population was analyzed according to age at treatment initiation, categorized into younger (<65 years) and older (≥65 years) subcohorts. Analyses were conducted from May 2019 to February 2020. Exposures: Use of BZDRs, modeled from register-based data using the PRE2DUP (from prescriptions to drug use periods) method. Main Outcomes and Measures: Long-term BZDR use, defined as continuous use of 180 days or longer, and factors associated with long-term vs short-term use, compared using Cox proportional hazards models. Results: Among the 129 732 incident BZDR users, the mean (SD) age was 52.6 (17.7) years, and 78 017 (60.1%) individuals were women. During the follow-up period, 51 099 BZDR users (39.4%) became long-term users. Long-term treatment was more common in the older subcohort (19 103 individuals [54.5%]) than the younger subcohort (31 996 individuals [33.8%]). At 6 months, 28 586 individuals (22.0%) had become long-term users: 11 805 (33.7%) in the older subcohort and 16 781 (17.7%) in the younger subcohort. The largest proportions of initiators who became long-term users were those persons who initiated treatment with nitrazepam (76.4%; 95% CI, 73.6%-79.1%), temazepam (63.9%; 95% CI, 62.9%-65.0%), lorazepam (62.4%; 95% CI, 59.7%-65.1%), or clonazepam (57.5%; 95% CI, 55.9%-59.2%). Factors associated with the development of long-term use included male sex, older age, receipt of social benefits, psychiatric comorbidities, and substance abuse. Conclusions and Relevance: The findings of this population-based cohort study conducted in Finland suggest that the incidence of subsequent long-term BZDR use in individuals who initiate use of BZDRs is high, especially among older persons, and that the specific BZDR used initially is associated with the development of long-term BZDR use and should be carefully considered when prescribing BZDRs. The observed factors that appear to be associated with development of long-term BZDR use also should be considered in clinical decision-making when starting and monitoring BZDR treatment.


Assuntos
Benzodiazepinas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Adulto Jovem
4.
J Clin Psychiatry ; 81(6)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991792

RESUMO

OBJECTIVE: There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD). METHODS: Secondary analyses of data from 2 clinical trials of antidepressant pharmacotherapy for GAD (escitalopram vs placebo, 2006-2009) or MDD (open treatment with venlafaxine, 2009-2014) were conducted. Participants included 640 adults aged 60+ years with DSM-IV-defined GAD (n = 177) or MDD (n = 463). Benzodiazepine data were collected at baseline. Adherence and treatment response were assessed over 12 weeks. The analysis addressed whether coprescribed benzodiazepines are associated with treatment response, antidepressant medication adherence, dropout, final dose of antidepressant medication, and report of antidepressant-related adverse effects. RESULTS: Participants with GAD and coprescribed benzodiazepines were treated with a lower mean dosage of escitalopram and were less likely to complete the trial; there was no difference in adherence or treatment response. Participants with MDD and coprescribed benzodiazepines were less likely to tolerate a therapeutic dose of venlafaxine and reported more medication-related adverse effects; there was no difference in adherence, dropout, or treatment response. CONCLUSIONS: Coprescription of benzodiazepines was associated with increased dropout in older patients with GAD and more medication-related adverse effects in older patients with MDD. However, with the systematic clinical attention offered in a clinical trial, they do not impede treatment response. Clinicians should be aware that a coprescribed benzodiazepine may be a marker of a more challenging treatment course. Trial Registration: Data analyzed were from studies with ClinicalTrials.gov identifiers NCT00892047 and NCT00105586.


Assuntos
Envelhecimento , Antidepressivos de Segunda Geração/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/farmacologia , Citalopram/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Cloridrato de Venlafaxina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Citalopram/administração & dosagem , Citalopram/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos
6.
PLoS One ; 15(9): e0238723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32916693

RESUMO

The aim of this study was to examine the risk of falls associated with the use of non-gamma amino butyric acid (GABA) sleep medications, suvorexant and ramelteon. This case-control and case-crossover study was performed at the Kudanzaka Hospital, Chiyoda Ward, Tokyo. A total of 325 patients who had falls and 1295 controls matched by sex and age were included. The inclusion criteria for the case group were hospitalized patients who had their first fall and that for the control were patients who were hospitalized and did not have a fall, between January 2016 and November 2018. The internal sleep medications administered were classified as suvorexant, ramelteon, non-benzodiazepines, benzodiazepines, or kampo. In the case-control study, age, sex, clinical department, the fall down risk score, and hospitalized duration were adjusted in the logistic regression model. In the case-control study, multivariable logistic regression showed that the use of suvorexant (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.29-5.28), nonbenzodiazepines (OR: 2.49, 95% CI: 1.73-3.59), and benzodiazepines (OR: 1.65, 95% CI: 1.16-2.34) was significantly associated with an increased OR of falls. However, the use of ramelteon (OR: 1.40, 95% CI: 0.60-3.16) and kampo (OR: 1.55, 95% CI: 0.75-3.19) was not significantly associated with an increased OR of falls. In the case-crossover study, the use of suvorexant (OR: 1.78, 95% CI: 1.05-3.00) and nonbenzodiazepines (OR: 1.63, 95% CI: 1.17-2.27) was significantly associated with an increased OR of falls. Similar patterns were observed in several sensitivity analyses. It was suggested that suvorexant increases the OR of falls. This result is robust in various analyses. This study showed that the risk of falls also exists for non-GABA sleep medication, suvorexant, and thus it is necessary to carefully prescribe hypnotic drugs under appropriate assessment.


Assuntos
Acidentes por Quedas , Azepinas/efeitos adversos , Indenos/efeitos adversos , Medicamentos Indutores do Sono/efeitos adversos , Triazóis/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Azepinas/administração & dosagem , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Estudos Cross-Over , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Indenos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sono/efeitos dos fármacos , Sono/fisiologia , Triazóis/administração & dosagem
7.
Medicine (Baltimore) ; 99(27): e20765, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629656

RESUMO

BACKGROUND: Remimazolam is a newly developed benzodiazepine as an alternative of conventional sedatives in the procedure of anesthesia. For the purpose of evaluating the efficacy and safety of remimazolam sedation during an endoscopy, we will perform a systematic review and meta-analysis of randomized controlled trials that compared remimazolam with midazolam and/or placebo. METHODS: We will search PubMed, Embase, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception to December 2019 for randomized controlled trials that investigated efficacy and safety of remimazolam during an endoscopy. The job will be performed without language restriction. Experimental groups will include the interventions of remimazolam, while control groups will involve midazolam, placebo, or no controls. The primary outcome will be the onset time, followed by the secondary outcomes of the recovery time, the incidence of hypotension, the incidence of hypoxia and the incidence of bradycardia. Relative ratio or standardized mean difference will be used to measure the effect size of remimazolam. We will use I statistics to assess the between-study heterogeneity in each meta-analysis, Eager's test to detect publication bias. RESULTS: The results of this study will be published in a peer-reviewed journal. ETHICS AND DISSEMINATION: There is no need for ethical approval because all data used in this meta-analysis have been published. In addition, all data will be analyzed anonymously during the review process. PROTOCOL REGISTRATION NUMBER: CRD42020170745.


Assuntos
Analgesia/métodos , Benzodiazepinas , Sedação Consciente/métodos , Hipnóticos e Sedativos , Analgesia/efeitos adversos , Benzodiazepinas/efeitos adversos , Sedação Consciente/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos
8.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680879

RESUMO

OBJECTIVES: Cardiorespiratory and pulse oximetry monitoring in children who are hospitalized should balance benefits of detecting deterioration with potential harms of alarm fatigue. We developed recommendations for monitoring outside the ICU on the basis of available evidence and expert opinion. METHODS: We conducted a comprehensive literature search for studies addressing the utility of cardiorespiratory and pulse oximetry monitoring in common pediatric conditions and drafted candidate monitoring recommendations based on our findings. We convened a panel of nominees from national professional organizations with diverse expertise: nursing, medicine, respiratory therapy, biomedical engineering, and family advocacy. Using the RAND/University of California, Los Angeles Appropriateness Method, panelists rated recommendations for appropriateness and necessity in 3 sequential rating sessions and a moderated meeting. RESULTS: The panel evaluated 56 recommendations for intermittent and continuous monitoring for children hospitalized outside the ICU with 7 common conditions (eg, asthma, croup) and/or receiving common therapies (eg, supplemental oxygen, intravenous opioids). The panel reached agreement on the appropriateness of monitoring recommendations for 55 of 56 indications and on necessity of monitoring for 52. For mild or moderate asthma, croup, pneumonia, and bronchiolitis, the panel recommended intermittent vital sign or oximetry measurement only. The panel recommended continuous monitoring for severe disease in each respiratory condition as well as for a new or increased dose of intravenous opiate or benzodiazepine. CONCLUSIONS: Expert panel members agreed that intermittent vital sign assessment, rather than continuous monitoring, is appropriate management for a set of specific conditions of mild or moderate severity that require hospitalization.


Assuntos
Eletrocardiografia , Monitorização Fisiológica/métodos , Oximetria , Guias de Prática Clínica como Assunto , Transtornos Respiratórios/fisiopatologia , Testes de Função Respiratória , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Criança , Criança Hospitalizada , Técnica Delfos , Relação Dose-Resposta a Droga , Humanos , Oxigenoterapia , Respiração/efeitos dos fármacos , Transtornos Respiratórios/etiologia , Sepse/fisiopatologia
9.
BMC Public Health ; 20(1): 1149, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698851

RESUMO

BACKGROUND: Suicide rates have been climbing in the U.S., particularly in Rocky Mountain states such as Colorado. Benzodiazepines have been linked with suicidal ideation, but there have been few population level assessments of this link. We conducted a public health assessment to determine the epidemiology and prevalence of recent benzodiazepine exposure, among suicide deaths in Colorado from 2015 to 17. METHODS: This epidemiologic assessment linked Colorado's Prescription Drug Monitoring Program, death certificate data, and Violent Death Reporting System to determine patterns of benzodiazepine exposure among suicide deaths in Colorado between 2015 and 2017. Recent benzodiazepine exposure was defined as receiving a prescription within 30 days of death or having a positive toxicology screen post-mortem. RESULTS: Among the 3465 suicide deaths in Colorado between 2015 and 2017, 20% had recent benzodiazepine exposure, and nearly 50% of those also had recent opioid exposure. Recent benzodiazepine exposure was more common among females than males (34% versus 16%). Among suicide deaths, those who died via drug overdose were more likely to have had recent benzodiazepine exposure (48%), compared to suicides by firearm (17%), hanging/asphyxiation (13%) and all other methods (approximately 20%). CONCLUSIONS: Benzodiazepines have been linked to suicidal ideation, but population level assessments of benzodiazepine exposure among suicide deaths are rare. Our epidemiologic assessment indicates a relatively high prevalence of recent benzodiazepine exposure that warrants further investigation from both clinical and public health perspectives.


Assuntos
Benzodiazepinas/efeitos adversos , Prescrições de Medicamentos/estatística & dados numéricos , Saúde Pública/estatística & dados numéricos , Comportamento Autodestrutivo/mortalidade , Suicídio/estatística & dados numéricos , Adulto , Analgésicos Opioides/efeitos adversos , Autopsia , Colorado/epidemiologia , Overdose de Drogas/etiologia , Overdose de Drogas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Comportamento Autodestrutivo/induzido quimicamente , Ideação Suicida
10.
Br J Anaesth ; 125(2): 159-167, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32571568

RESUMO

BACKGROUND: Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of ∼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs. METHODS: National data from the Information Service Division, NHS Scotland were analysed for prescribing, sociodemographic, and mortality data from the Health Informatics Centre, University of Dundee. DRDs in which gabapentinoids were implicated were identified from National Records of Scotland and Tayside Drug Death Databases. RESULTS: From 2006 to 2016, the number of gabapentin prescriptions in Scotland increased 4-fold (164 630 to 694 293), and pregabalin 16-fold (27 094 to 435 490). In 2016 'recurrent users' (three or more prescriptions) had mean age 58.1 yr, were mostly females (62.5%), and were more likely to live in deprived areas. Of these, 60% were co-prescribed an opioid, benzodiazepine, or both (opioid 49.9%, benzodiazepine 26.8%, both 17.1%). The age-standardised death rate in those prescribed gabapentinoids was double that in the Scottish population (relative risk 2.16, 95% confidence interval 2.08-2.25). Increases in gabapentinoids contributing to cause of DRDs were reported regionally and nationally (gabapentin 23% vs 15%; pregabalin 21% vs 7%). In Tayside, gabapentinoids were implicated in 22 (39%) of DRDs, 17 (77%) of whom had not received a prescription. CONCLUSIONS: Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death (including DRDs). Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication.


Assuntos
Analgésicos Opioides/efeitos adversos , Benzodiazepinas/efeitos adversos , Overdose de Drogas/epidemiologia , Gabapentina/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Pregabalina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Escócia/epidemiologia , Fatores Sexuais , Adulto Jovem
11.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32499386

RESUMO

BACKGROUND: Benzodiazepines are commonly prescribed to treat anxiety disorders and have been associated with falls and fractures in older adults. It is unknown whether benzodiazepines increase fracture risk in youth. We examined whether youth with anxiety disorders initiating benzodiazepine treatment have an increased risk of fractures compared with youth initiating selective serotonin reuptake inhibitors (SSRIs). METHODS: We used claims from commercially insured children (6-17 years) and young adults (18-24) with a recent anxiety disorder diagnosis, initiating benzodiazepines or SSRIs (2008-2016). Youth were followed until fracture, treatment discontinuation or switching, disenrollment, 3 months, or December 31, 2016. The primary end point was diagnostic codes for upper and lower limb fractures. Incident fracture rates, incident rate ratios (IRRs), and incident rate differences (IRDs) were estimated with propensity score inverse probability of treatment weighting. RESULTS: The cohort included 120 715 children and 179 768 young adults. In children, crude fracture rates during treatment were 33.1 per 1000 person-years (PYs) for benzodiazepine initiators and 25.1 per 1000 PYs for SSRI initiators. Adjusted IRR and IRD were 1.53 (95% confidence interval [CI]: 0.94-2.50) and 13.4 per 1000 PYs. Risk was heightened in children initiating long-acting benzodiazepines versus SSRIs (adjusted IRR = 2.30 [95% CI: 1.08-4.91]). Fracture rates were lower in young adults, with minimal differences between treatments (adjusted IRR = 0.85 [95% CI: 0.57-1.27]; adjusted IRD = -1.3 per 1000 PYs). CONCLUSIONS: An increased rate of fractures in children, but not young adults, with anxiety disorders initiating benzodiazepine treatment compared to SSRI treatment suggests a need for increased caution in the weeks after benzodiazepine initiation in children.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/epidemiologia , Inibidores de Captação de Serotonina/efeitos adversos , Adolescente , Benzodiazepinas/uso terapêutico , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Medição de Risco , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
12.
J Clin Psychiatry ; 81(4)2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32526104

RESUMO

OBJECTIVE: Antipsychotic drugs are known to increase mortality among patients with dementia. Many patients receive concomitant treatment with other psychotropic agents. The aim of this retrospective cohort study was to investigate the impact of benzodiazepines and antidepressants on the risk of death in patients with dementia initiating antipsychotic drug treatment. METHODS: Nationwide registry data on all incident dementia cases among individuals aged 65 years and older in Denmark between 2009 and 2013 for which antipsychotic treatment was initiated were used. The 180-day mortality was evaluated by crude and adjusted hazard ratios (HRs, including adjustment for somatic and psychiatric comorbidity, other prescription drugs, nursing home residency, and time since diagnosis), comparing periods of antipsychotic treatment with periods of concomitant treatment with benzodiazepines or antidepressants. RESULTS: Among 41,494 incident dementia cases, antipsychotic treatment was initiated for 10,291 (24.8%). After 3,140 people were excluded due to recent antipsychotic drug use or hospitalization, 7,151 people were included in the analysis. The total follow-up time during current antipsychotic treatment was 1,146 person-years, and 831 died during antipsychotic treatment. Compared with antipsychotic treatment alone, the risk of death increased during antipsychotic treatment in combination with benzodiazepines (adjusted HR = 2.19; 95% CI, 1.83-2.63), while there was a decreased risk of death during antipsychotic treatment in combination with antidepressants (adjusted HR = 0.61; 95% CI, 0.50-0.74). CONCLUSIONS: The diverse impact of concomitant use of benzodiazepines and antidepressants on mortality may be due to a direct drug-related effect. Alternatively, the findings could reflect differential mortality associated with different indications for therapy. Although the results cannot prove causality, and there may be residual confounding, clinicians should be cautious when considering the combination of antipsychotics and benzodiazepines in patients with dementia.


Assuntos
Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Demência/mortalidade , Quimioterapia Combinada/mortalidade , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Demência/tratamento farmacológico , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
13.
Ann Biol Clin (Paris) ; 78(4): 438-440, 2020 08 01.
Artigo em Francês | MEDLINE | ID: mdl-32576545

RESUMO

Hyperprolactinemia is common and accounts for 20 to 25% of secondary amenorrhea causes. Here, we report a case of moderate hyperprolactinemia observed in a 40-year-old patient consulting for spaniomenorrhea and inguinal pain during a bartholinitis episode. After eliminating all known causes of hyperprolactinemia, alprazolam intake is finally assumed. This hyperprolactinemia is found in a few bibliographic studies and is also noted in the summary of product characteristics. However, benzodiazepines are not known as hyperprolactinemia-inducing drugs by the endocrinologists and do not appear in the list of drugs established by a consensus of experts from the French Society of Endocrinology. This article aims to increase awareness of prescribing physicians and biologists of the possible occurrence of hyperprolactinemia in patients treated by benzodiazepines, especially since the intake of this molecule is particularly common in France, whether it is a medical prescription or self-medication.


Assuntos
Alprazolam/efeitos adversos , Benzodiazepinas/efeitos adversos , Hiperprolactinemia/induzido quimicamente , Adulto , Amenorreia/induzido quimicamente , Amenorreia/complicações , Feminino , Humanos , Hiperprolactinemia/complicações
14.
JAMA Netw Open ; 3(4): e202051, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32242907

RESUMO

Importance: Benzodiazepines, which are associated with safety-related harms for older adults, were not covered when the US Medicare Part D prescription drug benefit began. Coverage was extended to benzodiazepines in 2013. Objective: To examine whether the expansion of benzodiazepine coverage among Medicare Advantage (MA) beneficiaries was associated with increases in fall-related injuries or overdoses among older adults. Design, Setting, and Participants: This ecological study used interrupted time-series with comparison-series analyses of MA claims data from 4 635 312 age-eligible MA beneficiaries and 940 629 commercially insured individuals (comparison group) stratified by age (65-69, 70-74, 75-79, and ≥80 years) to separately compare trends in fall-related injury and overdose before (January 1, 2010, to December 31, 2012) and after (January 1, 2013, to December 31, 2015) coverage expansion for benzodiazepines. Data analysis was performed from September 1, 2018, to August 31, 2019. Exposures: Expansion of benzodiazepine coverage in Medicare Part D in 2013. Main Outcomes and Measures: Monthly rate of fall-related injury and overdose. Results: In 2012 (the year before the policy change), women constituted 57.5% of the MA group and 47.4% of the comparison group. A total of 25.8% of individuals in the MA group were aged 65 to 69 years, and 29.3% were 80 years or older (mean [SD], 75.1 [6.4] years); 56.7% of individuals in the comparison group were aged 65 to 69 years, and 15.1% were 80 years or older (mean [SD] age, 70.9 [6.5] years). In the MA group, 4 635 312 individuals contributed 156 754 749 person-months from 2010 through 2015; in the comparison group, 940 629 individuals contributed 25 104 534 person-months. After coverage of benzodiazepines began, the rate (ie, slope) of fall-related injury among MA beneficiaries increased from before to after coverage among all age groups. Compared with the comparison group, the increase in rate was statistically significant for those 80 years or older (rate changes for the MA vs comparison groups: 0.12 [95% CI, 0.07 to 0.17] vs -0.01 [95% CI, -0.11 to 0.10]; P = .04 for interaction). The overdose trend changed from decreasing to increasing among MA beneficiaries after coverage for all age groups, with a statistically significant increase compared with the comparison group among those aged 65 to 69 years (rate changes for the MA vs comparison groups: 0.23 [95% CI, 0.17 to 0.30] vs 0.02 [95% CI, -0.06 to 0.11]; P < .001 for interaction) and among those 80 years or older (rate changes for the MA vs comparison groups: 0.07 [95% CI, 0.00 to 0.14] vs -0.20 [95% CI, -0.35 to -0.05]; P = .002 for interaction). Results among MA beneficiaries were consistent when stratified by sex and when limited to those prescribed opioids. Conclusions and Relevance: Medicare's expansion of benzodiazepine coverage may have been associated with increases in the rates of overdose among adults ages 65 to 69 years and in the rates of overdose and fall-related injury among those 80 years or older.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Benzodiazepinas/efeitos adversos , Benefícios do Seguro/tendências , Cobertura do Seguro/estatística & dados numéricos , Medicare Part D/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Benzodiazepinas/uso terapêutico , Estudos de Casos e Controles , Overdose de Drogas/epidemiologia , Feminino , Humanos , Benefícios do Seguro/economia , Análise de Séries Temporais Interrompida , Masculino , Medicare Part C , Medicare Part D/economia , Segurança do Paciente , Medicamentos sob Prescrição/efeitos adversos , Medicamentos sob Prescrição/provisão & distribução , Estados Unidos/epidemiologia
15.
JAMA Netw Open ; 3(4): e202361, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271389

RESUMO

Importance: The use of benzodiazepines or alcohol together with opioids increases overdose risk, but characterization of co-involvement by predominant opioid subtype is incomplete to date. Understanding the use of respiratory depressants in opioid overdose deaths (OODs) is important for prevention efforts and policy making. Objective: To assess the prevalence and number of alcohol- or benzodiazepine-involved OODs by opioid subtypes in the United States from 1999 to 2017. Design and Setting: This repeated cross-sectional analysis used data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database of all opioid-involved poisoning deaths from January 1, 1999, to December 31, 2017, for the United States. State-level binge drinking prevalence rates for 2015 to 2017 were obtained from the Behavior Risk Factor Surveillance System of the Centers for Disease Control and Prevention, and benzodiazepine prescribing rates for 2012 (most recent available data) were obtained from IMS Health, a commercial database. Data were analyzed from July 10, 2018, to May 16, 2019. Main Outcomes and Measures: Prevalence of alcohol or benzodiazepine co-involvement for all OODs and by opioid subtype, nationally and by state. Results: From 1999 to 2017, 399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years. Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017. Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r = 0.34; P = .02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r = 0.57; P < .001). Conclusions and Relevance: This study found that alcohol and benzodiazepine co-involvement in opioid-involved overdose deaths was common, varied by opioid subtype, and was associated with state-level binge drinking and benzodiazepine prescribing rates. These results may inform state policy initiatives in harm reduction and overdose prevention efforts.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Analgésicos Opioides/envenenamento , Benzodiazepinas/efeitos adversos , Overdose de Drogas/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologia
18.
Anesthesiology ; 133(1): 119-132, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32349070

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. METHODS: The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. RESULTS: The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). CONCLUSIONS: Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Delírio do Despertar/induzido quimicamente , Delírio do Despertar/epidemiologia , Idoso , Benzodiazepinas/efeitos adversos , Estudos de Coortes , Confusão/etiologia , Confusão/psicologia , Cuidados Críticos , Delírio do Despertar/prevenção & controle , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Pontuação de Propensão
20.
Drugs ; 80(6): 625-633, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32274703

RESUMO

Remimazolam (Anerem® in Japan; ByFavo™ in the USA; Aptimyda™ in the EU) is an ultra-short-acting intravenous (IV) benzodiazepine sedative/anesthetic being developed by PAION AG in conjunction with a number of commercial partners for use in anesthesia and procedural sedation. Remimazolam was approved on 23 January 2020 in Japan for use in general anesthesia in adult patients. Remimazolam is also undergoing regulatory assessment in South Korea for this indication and for use in procedural sedation in the USA, the EU and China. This article summarises the major milestones in the development of remimazolam for this first approval for the induction and maintenance of general anaesthesia, and its potential upcoming approvals in general anaesthesia and procedural sedation.


Assuntos
Anestesia Geral , Anestésicos Intravenosos/uso terapêutico , Benzodiazepinas/uso terapêutico , Aprovação de Drogas , Hipnóticos e Sedativos/uso terapêutico , Anestesia Geral/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/química , Animais , Benzodiazepinas/efeitos adversos , Benzodiazepinas/química , Colonoscopia , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/química , Conformação Molecular
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