Antipsychotics-Associated Serious Adverse Events in Children: An Analysis of the FAERS Database

Abstract

Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess serious adverse events induced by the administration of antipsychotics to children.Methods: Following pre-processing of FAERS data by elimination of duplicated records as well as adjustments to standardize drug names, reports involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone, risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in the data that signified a drug-associated adverse event were detected via quantitative data mining algorithms. The algorithms applied to this study include the empirical Bayes geometric mean, the reporting odds ratio, the proportional reporting ratio, and the information component of a Bayesian confidence propagation neural network. Neuroleptic malignant syndrome (NMS), QT prolongation, leukopenia, and suicide attempt were focused on as serious adverse events.Results: In regard to NMS, the signal scores for haloperidol and aripiprazole were greater than for other antipsychotics. Significant signals of the QT prolongation adverse event were detected only for ziprasidone and risperidone. With respect to leukopenia, the association with clozapine was noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole were detected.Conclusions: It was suggested that there is a level of diversity in the strength of the association between various first- and second-generation antipsychotics with associated serious adverse events, which possibly lead to fatal outcomes. We recommend that research be continued in order to gather a large variety and quantity of related information, and that both available and newly reported data be placed in the context of multiple medical viewpoints in order to lead to improved levels of care.

Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders

“…Quetiapine was examined in two systematic reviews and meta-analyses (38,80). We also identified published and unpublished data from 7 RCTs and 4 non-randomized studies (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(81)(82)(83)(84)(85)(86).…”

Aripiprazole for the management of schizophrenia in the Japanese population: a systematic review and meta-analysis of randomized controlled trials

“…Recently, studies reported that aripiprazole might be associated with an increased risk of neuroleptic malignant syndrome (NMS). 37 , 38 Despite performing a meta-analysis of NMS, we found no difference in this outcome between aripiprazole and the pooled antipsychotics. However, two patients receiving aripiprazole developed NMS during one study, 22 suggesting that clinicians should be vigilant for the development of NMS during aripiprazole therapy.…”

Aripiprazole-Induced Neutropenia in a Seven Year-Old Male: A Case Report

“…The FDA Adverse Event Reporting Event database found no significant association between aripiprazole and neutropenia in children [2]. Although, leukopenia is mentioned as a possible side effect of aripiprazole on its marketing brochure, very few cases have been reported in the clinical literature [5].…”

“…Immune reactions being a direct toxic effect on bone marrow and increased destruction of cells are possible mechanisms in the pathophysiology of these blood dyscrasias [1]. An association of clozapine with neutropenia and/or agranulocytosis is well established, while aripiprazole is considered relatively safe with rare hematological side effects [2]. In 2009, the Food and Drug Administration (FDA) approved aripiprazole for the treatment of irritability associated with autism spectrum disorder in children aged six to 17 years [3].…”