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Neurological and cardiovascular adverse events associated with antimanic treatment in children and adolescents.

ABSTRACT: To identify the factors associated with incident neurological and cardiovascular adverse events in children and adolescents treated with antimanic agents, a retrospective, longitudinal study was conducted. Medicaid medical and pharmacy claims between January 1996 and December 2005 were used to identify 3657 children and adolescents prescribed antimanic medications, and a random sample of 4500 children not treated with psychotropic medications. All adverse events examined (sedation/drowsiness, headaches, involuntary movements/extrapyramidal symptoms (EPS), cardiovascular events, hypertension, and orthostatic hypotension) were more prevalent in the antimanic-treated cohort. The odds of developing incident sedation/drowsiness and headaches were significantly higher for those prescribed carbamazepine, and co-prescribed selective serotonin reuptake inhibitors or antipsychotics. The odds of incident involuntary movements/EPS were significantly higher for those co-prescribed antimanic and antipsychotic agents, and those with comorbid central nervous system (CNS), organic brain disorders/mental retardation, or epilepsy. Incident cardiovascular events, hypertension, and orthostatic hypotension odds were significantly higher for those co-prescribed antimanic agents and antipsychotics, or those with comorbid epilepsy or metabolic conditions. Co-prescription of antimanic and antipsychotic agents is more likely associated with neurological and cardiovascular adverse reactions, especially in young patients with preexisting CNS/neurological disorders.

SUBMITTER: Jerrell JM

PROVIDER: S-EPMC6493784 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Neurological and cardiovascular adverse events associated with antimanic treatment in children and adolescents.

Jerrell Jeanette M JM

CNS neuroscience & therapeutics 20090921 1

To identify the factors associated with incident neurological and cardiovascular adverse events in children and adolescents treated with antimanic agents, a retrospective, longitudinal study was conducted. Medicaid medical and pharmacy claims between January 1996 and December 2005 were used to identify 3657 children and adolescents prescribed antimanic medications, and a random sample of 4500 children not treated with psychotropic medications. All adverse events examined (sedation/drowsiness, he ...[more]

PMID: 19769597

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Project description:Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively. Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI. Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.

Project description:BackgroundThe prescription of antipsychotics (AP), and especially second generation AP, is increasing worldwide in the pediatric population. Most prescriptions are off-label and despite the identification of frequent and potentially severe adverse events (AE), there are only a few guidelines for the safety management. France is one of the countries with no official safety guidelines.MethodsPsychotropic drug-naive adolescents (13-18 years), hospitalized for an acute psychotic episode and treated with a second-generation antipsychotic were consecutively included in a prospective cohort study. Patients were assessed for their AE at baseline, 2, 6 and 12 weeks after the introduction of drug.ResultsThe majority of patients was treated with risperidone (n = 13), 2 with aripiprazole. The principal findings are: (1) A high incidence of neuromuscular AE: 8/15 muscle weakness, 8/15 extrapyramidal syndrome, 6/15 akathisia, 3/15 oro-facial acute dystonia; (2) Severe catatonia symptoms in 2 patients despite a low to moderate treatment dose, requiring transfer in intensive care unit for one; (3) Weight gain and significant increase of the BMI for all 13 patients who had a 12 weeks follow-up.ConclusionAll adolescents experienced AE, with significant weight gain being observed in all patients who completed the 12-week follow-up. The fact that our patient population was first episode drug naïve may partially explain this observation. Despite the limitation due to the small sample size of this prospective short-term study, such findings are important to report and warrant further research.Clinical and research implicationBecause of the lack of naturalistic follow up studies of antipsychotic treatments in AP-naive children and adolescents and the absence of safety guidelines for the pediatric population in France, we decided to continue our research at a national level. We therefore started a prospective, naturalistic and multicenter study funded by the French National Agency for Medicines and Health Products Safety (ANSM). Study purpose is to evaluate the incidence of adverse events related to antipsychotic drugs in AP-naive children and adolescents. In addition, we aim to provide further evidence for the necessity of national safety guidelines for AP prescription in the pediatric population.

Project description:ImportanceRituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children.ObjectiveTo describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people.Design, setting, and participantsThis retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020.ExposureOne or more doses of rituximab.Main outcomes and measuresAdverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events.ResultsWe identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM.Conclusions and relevanceRituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.

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Dataset Information

Neurological and cardiovascular adverse events associated with antimanic treatment in children and adolescents.

Publications

Neurological and cardiovascular adverse events associated with antimanic treatment in children and adolescents.

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