Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.559
Filtrar
1.
Medicina (Kaunas) ; 57(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34441022

RESUMO

BACKGROUND AND OBJECTIVES: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. MATERIALS AND METHODS: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. RESULTS: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. CONCLUSIONS: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Leucocitose/induzido quimicamente , Leucocitose/tratamento farmacológico , Prevalência , Esquizofrenia/tratamento farmacológico
2.
BMJ Case Rep ; 14(8)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400419

RESUMO

We report a 21-year-old man with bipolar disorder who was on a stable dose of escitalopram and risperidone. Tramadol and cough syrup (dextromethorphan) were added for his recent attack of upper respiratory tract infection. However, he developed various neurological symptoms. Haloperidol and ondansetron were added after hospitalisation. However, his condition deteriorated. A diagnosis of serotonin syndrome (SS) was made, and cyproheptadine was started. Cyproheptadine provided relief in most of the symptoms within 48 hours except for the presence of fever and rigidity. The addition of bromocriptine provided a complete resolution of the symptoms. We considered the presence of both SS and neuroleptic malignant syndrome (NMS) in this case. There are four similar cases in the literature. We discussed a diagnostic and therapeutic approach for patients who are on both serotonergic agents and neuroleptics and develop SS-like or NMS-like clinical features.


Assuntos
Antipsicóticos , Síndrome Maligna Neuroléptica , Síndrome da Serotonina , Adulto , Antipsicóticos/efeitos adversos , Haloperidol , Humanos , Masculino , Síndrome Maligna Neuroléptica/diagnóstico , Síndrome Maligna Neuroléptica/etiologia , Risperidona/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/diagnóstico , Adulto Jovem
3.
Syst Rev ; 10(1): 214, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340713

RESUMO

BACKGROUND: Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. METHODS: We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group's Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. DISCUSSION: This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175414.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Humanos , Metanálise como Assunto , Metanálise em Rede , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Revisões Sistemáticas como Assunto
7.
Asian J Psychiatr ; 62: 102745, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216977

RESUMO

OBJECTIVES: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction. METHODS: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction. RESULTS: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction. CONCLUSION: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.


Assuntos
Antipsicóticos , Clozapina , Antipsicóticos/efeitos adversos , Estudos de Casos e Controles , Clozapina/efeitos adversos , Humanos , Japão , Estudos Retrospectivos , Fatores de Risco
8.
Tijdschr Psychiatr ; 63(6): 406-411, 2021.
Artigo em Holandês | MEDLINE | ID: mdl-34231858

RESUMO

Clozapine is an antipsychotic with clozapine-induced agranulocytosis (CIA) as a rare, but potentially life-threatening side-effect, for which the white blood cell count and absolute neutrophil count are routinely monitored. Observed leukopenia may lead to more frequent monitoring, or even acute discontinuation of clozapine treatment. COVID-19 may cause deviating blood parameters such as leukopenia, and more exceptionally even granulocytopenia, just as clozapine does. In case of a SARS-CoV-2 infection and leukopenia, it is important to differentiate whether the reduced white blood cell count is caused by clozapine - in which case it needs to be stopped immediately - or as a consequence of infection with the coronavirus. In case of a mild leukopenia, based on a lymphopenia, clozapine can be safely continued with more frequent blood monitoring. Additionally, the dosage of clozapine should be reduced by half, due to the risk of a sudden increase of clozapine serum levels.


Assuntos
Antipsicóticos , COVID-19 , Clozapina , Leucopenia , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , SARS-CoV-2 , Esquizofrenia/tratamento farmacológico
10.
Forensic Sci Int ; 325: 110889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225211

RESUMO

Medication-induced prolongation of the QT-interval (miQTP) can lead to cardiac arrhythmia. Our aim was to investigate the prevalence of forensic autopsy cases where fatal cardiac arrhythmia related to treatment with QT-prolonging medications (QT-PMs) could be suspected. We performed a cross-sectional study of 741 forensic autopsies undertaken at our institution in non-drug addicts aged 15 years or above from 2017 to 2019. We defined a high risk of miQTP by one detected QT-PM in a concentration above therapeutic level, or two or more detected QT-PMs in post mortem blood. We reviewed the autopsy reports from cases with a high miQTP-risk to identify cases with no other apparent cause of death. We discarded suicides and cases with lethal levels of QT-PMs. We identified 167 cases (22.5%) with high risk of miQTP, and discarded 36 suicides (4.9%) and 7 (0.9%) with lethal levels of QT-PMs. Apart from a high risk of miQTP, no other apparent explanation of the cause of death was present in seven (0.9%). In 18 cases (2.4%) with high miQTP-risk, the cause of death was primarily attributed to cardiac changes other than acute cardiovascular events. In conclusion, 22.5% had a high risk of miQTP, and fatal cardiac arrhythmia related to treatment with QT-PMs could be suspected in 0.9%. However, a genetic pro-arrhythmic background could not be excluded in our study. Furthermore, it is possible that QT-PMs could have played a role in some of the 2.4% of cases where the cause of death was mainly attributed to cardiac changes and the risk of miQTP was high.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/sangue , Anestésicos/efeitos adversos , Anestésicos/sangue , Antidepressivos/efeitos adversos , Antidepressivos/sangue , Antieméticos/efeitos adversos , Antieméticos/sangue , Antipsicóticos/efeitos adversos , Antipsicóticos/sangue , Autopsia , Estudos Transversais , Dinamarca , Diuréticos/efeitos adversos , Diuréticos/sangue , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/sangue , Humanos , Masculino , Pessoa de Meia-Idade
11.
BMJ Case Rep ; 14(7)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330723

RESUMO

Lithium is an effective mood stabiliser used to treat bipolar affective disorder (BPAD); however, it can also adversely affect the kidneys, causing acute toxic effects, nephrogenic diabetes insipidus, chronic renal dysfunction and end-stage kidney disease (ESKD) in a minority of patients. We describe the case of a man with a 34-year history of BPAD type-1 and a 2-year history of ESKD secondary to lithium-induced nephropathy who experienced a manic relapse. He previously responded well to lithium but, following a deterioration in kidney function, was switched to olanzapine and sodium valproate. This precipitated a period of instability, which culminated in a treatment-resistant manic episode requiring hospital admission. After a multidisciplinary team discussion, lithium therapy was restarted and provided remission. This was achieved safely through a reduced dosing schedule of three times a week post dialysis, slow dose titration and blood level monitoring prior to each dialysis session.


Assuntos
Antipsicóticos , Transtorno Bipolar , Nefropatias , Antimaníacos/efeitos adversos , Antipsicóticos/efeitos adversos , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Nefropatias/tratamento farmacológico , Lítio/efeitos adversos , Masculino , Transtornos do Humor , Recidiva Local de Neoplasia/tratamento farmacológico , Diálise Renal , Ácido Valproico/efeitos adversos
12.
Handb Clin Neurol ; 179: 371-382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34225976

RESUMO

Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect profile, which resembles the metabolic syndrome, represents a significant clinical problem that increases morbidity and limits treatment adherence. Moreover, the mechanisms involved in antipsychotic-induced adverse metabolic effects (AMEs) are unknown and mitigating strategies and interventions are limited. However, recent clinical trials show that nightly administration of exogenous melatonin may mitigate or even prevent antipsychotic-induced AMEs. This clinical evidence in combination with recent preclinical data implicate the circadian system in antipsychotic-induced AMEs and their mitigation. In this chapter, we provide an overview on the circadian system and its involvement in antipsychotic-induced AMEs, as well as the potential beneficial effect of nightly melatonin administration to mitigate them.


Assuntos
Antipsicóticos , Melatonina , Transtornos Mentais , Síndrome Metabólica , Antipsicóticos/efeitos adversos , Humanos , Melatonina/uso terapêutico , Transtornos Mentais/tratamento farmacológico
13.
Alzheimers Res Ther ; 13(1): 131, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271969

RESUMO

BACKGROUND: Many patients with Alzheimer's disease (AD) are physically frail or have substantial functional impairments. There is growing evidence that such patients are at higher risk for medication-induced adverse events. Furthermore, frailty seems to be more predictive of poor clinical outcomes than chronological age alone. To our knowledge, no systematic review of clinical trials examining drug therapy of AD or behavioural and psychological symptoms of dementia (BPSD) has specifically focused on the topic of physical frailty. Our objective was to evaluate the efficacy and safety of pharmacotherapy in AD patients with frailty or significant functional impairments. METHODS: We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) of drug therapy of AD and BPSD in patients with significant functional impairments according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Cochrane research criteria. Significant functionally impaired patient populations were identified using the recommendations of the Medication and Quality of Life in frail older persons (MedQoL) Research Group. Screening, selection of studies, data extraction and risk of bias assessment were performed independently by two reviewers. Outcomes including functional status, cognitive function, changes in BPSD symptoms, clinical global impression and quality of life were analysed. For assessing harm, we assessed adverse events, drop-outs as a proxy for treatment tolerability and death. Results were analysed according to Cochrane standards and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 45,045 search results, 38,447 abstracts and 187 full texts were screened, and finally, 10 RCTs were included in the systematic review. Selected articles evaluated pharmacotherapy with acetylcholinesterase-inhibitors (AChEI), anticonvulsants, antidepressants and antipsychotics. Studies of AChEIs suggested that patients with significant functional impairments had slight but significant improvements in cognition and that AChEIs were generally well tolerated. Studies of antidepressants did not show significant improvements in depressive symptoms. Antipsychotics and anticonvulsants showed small effects on some BPSD items but also higher rates of adverse events. However, due to the very small number of identified trials, the quality of evidence for all outcomes was low to very low. Overall, the small number of eligible studies demonstrates that significantly functional impaired older patients have not been adequately taken into consideration in most clinical trials investigating drug therapy of AD and BPSD. CONCLUSION: Due to lack of evidence, it is not possible to give specific recommendations for drug therapy of AD and BSPD in frail older patients or older patients with significant functional impairments. Therefore, clinical trials focussing on frail older adults are urgently required. A standardized approach to physical frailty in future clinical studies is highly desirable.


Assuntos
Doença de Alzheimer , Antipsicóticos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/efeitos adversos , Inibidores da Colinesterase/uso terapêutico , Cognição , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204223

RESUMO

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient's pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.


Assuntos
Citocromo P-450 CYP2D6/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Variantes Farmacogenômicos , Fumarato de Quetiapina/efeitos adversos , Alelos , Antipsicóticos/efeitos adversos , Antipsicóticos/química , Antipsicóticos/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Estudos de Associação Genética , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Fumarato de Quetiapina/administração & dosagem , Fumarato de Quetiapina/química , Fumarato de Quetiapina/metabolismo , Índice de Gravidade de Doença
15.
Clin Pharmacol Ther ; 110(3): 582-588, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34129738

RESUMO

Pharmacogenetics (PGx) research over the past 2 decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of these findings to optimize treatment outcomes for patients in clinical practice has been limited. This paper presents a meta-review of key PGx findings related to antipsychotic response and common adverse effects, including antipsychotic-induced weight gain, tardive dyskinesia (TD), and clozapine-induced agranulocytosis (CIAG), and highlights advances and challenges in clinical implementation. Most robust findings from candidate gene and genomewide association studies were reported for associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. As a result, product labels and guidelines from various PGx expert groups have provided selection and dosing recommendations based on CYP2D6 metabolizer phenotypes for commonly prescribed antipsychotics. Other interesting genetic targets include DRD2 for antipsychotic response, SLC18A2 for TD, and the human leukocyte antigen (HLA) genes, HLA-DQB1 and HLA-B, for CIAG. Well-designed studies using large, well-characterized samples that leverages international collaborations are needed to validate previous findings, as well as discover new genetic variants involved in antipsychotic response and adverse effects.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Citocromo P-450 CYP2D6/genética , Variação Genética/efeitos dos fármacos , Variação Genética/genética , Antígenos HLA-B/genética , Humanos , Farmacogenética/métodos , Resultado do Tratamento
16.
J Psychiatr Res ; 141: 116-123, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34192602

RESUMO

Clozapine is the only effective antipsychotic drug used for the treatment of treatment-resistant schizophrenia. Although it has been shown that the frequency of clozapine use is very low in Japan, our previous study revealed that the number of clozapine prescriptions has been increasing in recent years, and that risk factors leading to discontinuation of clozapine were also identified as age ≥40 years, poor tolerability to olanzapine, previous treatment with clozapine, and white blood cell count <6000/mm3. The main cause for discontinuation of clozapine is the occurrence of a wide range of adverse events, including neutropenia/leukopenia and fatal cardiac disorders. In this study, we analyzed the physical details and backgrounds of patients with adverse events that led to clozapine discontinuation using a national registry database of more than 8000 Japanese patients. The physical adverse events that led to discontinuation of clozapine were neutropenia/leukopenia, glucose intolerance, cardiac disorders, gastrointestinal disorders, neuroleptic malignant syndrome, pleurisy, pulmonary embolism, sedation/somnolence, and seizures. Neutropenia/leukopenia had the highest incidence (5.0%). Neutropenia/leukopenia and cardiac disorders tended to occur early in the treatment period, indicating the need for careful monitoring for these adverse events in the early stages of clozapine treatment. Gastrointestinal disorders occurred over a long period of time, suggesting the need for careful observation during the maintenance period. The data obtained in our study will lead to the optimal and safe use of clozapine treatment.


Assuntos
Antipsicóticos , Clozapina , Neutropenia , Adulto , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Japão/epidemiologia , Sistema de Registros
17.
Medicine (Baltimore) ; 100(26): e26465, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190170

RESUMO

ABSTRACT: Acute dystonic reactions are a worrying reason for presentation to the pediatric emergency department and the pediatric neurology clinic in childhood. It must be diagnosed and treated quickly. The aim of this study was to examine the clinical presentations, etiological factors, and prognosis of patients presenting to our regional tertiary pediatric neurology clinic with a diagnosis of acute dystonic reactions in children.Nine pediatric patients who were treated for acute dystonic reactions between May, 2018 and May, 2020 and had adequate follow-up were included in the study. Medical record data were reviewed age, gender, etiology, features of family, treatment, and results.Three of the patients were female and 6 were male. Their average age was 11 years (4-17). All patients were evaluated as a drug-induced acute dystonic reaction. Of the 9 patients, 5 were due to metoclopramide, 3 were due to risperidone, and 1 was due to aripiprazole. It was learned that a similar situation against other drugs developed in the family history of 3 patients. As a treatment, all of them were intramuscularly applied biperiden suitable for their weight and 30 minutes dramatic improvement was observed. Additional dose had to be administered in only 1 case. All cases were discharged for 24 hours. No problem was observed in their follow-up.Drug-induced acute dystonic reaction can be diagnosed and has a clinical picture that completely resolves when effective treatment is applied. However, it should not be forgotten that it can reach life-threatening dimensions clinically.


Assuntos
Aripiprazol/efeitos adversos , Biperideno/administração & dosagem , Distonia , Metoclopramida/efeitos adversos , Risperidona/efeitos adversos , Idade de Início , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Criança , Suscetibilidade a Doenças , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/efeitos adversos , Distonia/induzido quimicamente , Distonia/diagnóstico , Distonia/tratamento farmacológico , Distonia/epidemiologia , Feminino , Humanos , Injeções Intramusculares , Masculino , Anamnese , Metoclopramida/administração & dosagem , Parassimpatolíticos/administração & dosagem , Risperidona/administração & dosagem , Resultado do Tratamento , Turquia/epidemiologia
18.
Autism Res ; 14(8): 1800-1814, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34080319

RESUMO

Risperidone and aripiprazole, commonly used antipsychotics in children with autism spectrum disorder (ASD), have previously been associated with elevated fracture risk in other populations. The aim of this study was to evaluate and compare the risk of fracture among children with ASD using risperidone or aripiprazole. This was a retrospective, propensity-score matched cohort study, set between January 2013 and December 2018. We used the MarketScan Medicaid insurance data, which covers multiple states of the United States. We included ASD children aged 2-18 years, who were new users of aripiprazole or risperidone and with no prior history of antipsychotic use or fractures. The main exposure was the continued use of aripiprazole or risperidone. The incidence rates of any fracture during follow-up were evaluated, and the risk between aripiprazole and risperidone was compared via Cox-proportional hazard models. Results were stratified by age, sex, duration of exposure and fracture site. In total, 3312 patients (78% male; mean [SD] age 11.0 [3.7] years) were identified for each cohort. Over the full duration of follow-up, fracture incidence rates per 1000 patient-years were 23.2 for risperidone and 38.4 for aripiprazole (hazard ratio and 95% confidence interval: 0.60 [0.44-0.83]). Risks were similar between cohorts throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. Extremity fractures drove most of the increased risk, with the biggest differences in lower leg and ankle fractures. Differences widened for children aged 10 years or younger (HR [95% CI]: 0.47 [0.30-0.74]). In conclusion, compared to aripiprazole, risperidone was associated with 40% lower risk of fracture. Further analysis on the mechanism and long-term bone health of antipsychotic-treated children with ASD is warranted. LAY SUMMARY: We compared the risk of bone fractures among 6624 children with autism spectrum disorder (ASD), half of whom used risperidone and half of whom used aripiprazole. Taking other factors into account, risks were similar between the two groups throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. The biggest differences were in lower leg and ankle fractures. Overall, compared with aripiprazole, risperidone was associated with 40% lower risk of fracture.


Assuntos
Antipsicóticos , Transtorno do Espectro Autista , Fraturas Ósseas , Adolescente , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/epidemiologia , Criança , Estudos de Coortes , Feminino , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Risperidona/efeitos adversos , Estados Unidos/epidemiologia
19.
J Psychiatr Res ; 140: 409-415, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144444

RESUMO

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.


Assuntos
Antipsicóticos , Preparações Farmacêuticas , Esquizofrenia , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Feminino , Humanos , Metabolômica , Olanzapina , Esquizofrenia/tratamento farmacológico , Ganho de Peso
20.
BMC Psychiatry ; 21(1): 289, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082747

RESUMO

BACKGROUND: Parkinsonian symptoms are common adverse effects of antipsychotics. Older adults are particularly vulnerable to drug-induced parkinsonism. Nonetheless, parkinsonian symptoms in seniors treated with antipsychotics cannot be straightforwardly attributed to antipsychotic medication. A comprehensive diagnostic workup is necessary in many cases in order to shed light on the cause of such symptoms in this patient population. CASE SERIES: Eight cases of hospitalized depressed older adults with parkinsonian symptoms, who were treated for at least one year with antipsychotics, are reported. Based on neurological consultation, structural brain imaging and Ioflupane (I-123) dopamine transporter (DAT) single photon emission computerized tomography (SPECT), Parkinson's disease was diagnosed in one case, idiopathic tremor in another, vascular parkinsonism in another one, while in another individual parkinsonian symptoms persisted at 12-month post-discharge follow-up even though his/her symptoms were classified as drug-induced on discharge. In four patients, parkinsonian symptoms were definitely drug-induced and no movement disturbances were reported at follow-up. CONCLUSIONS: Differences in the cause and outcome of parkinsonian symptoms in seniors treated with antipsychotics merit systematic and in-depth study considering the therapeutic and prognostic implications of an accurate detection of the cause of such symptoms. Familiarizing clinical psychiatrists with these differences could pave the way towards approaching seniors with severe, atypical and/or persistent parkinsonian symptoms in a more individualized diagnostic and therapeutic manner, and towards more cautious prescribing of antipsychotics in this age group.


Assuntos
Antipsicóticos , Transtornos Parkinsonianos , Assistência ao Convalescente , Idoso , Antipsicóticos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Alta do Paciente , Tomografia Computadorizada de Emissão de Fóton Único
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...