No Apparent Cardiac Conduction Effects of Acute Treatment with Risperidone in Children with Autism Spectrum Disorder

Abstract

Objectives: Risperidone is approved for the treatment of serious behavioral problems in children with autism spectrum disorder (ASD). This study examined the effects of risperidone on cardiac conduction in children with ASD. Methods: Data were collected from an 8-week, five-site trial conducted by the Research Units on Pediatric Psychopharmacology Autism Network. Children (age 5-17 years) were randomly assigned to risperidone (n = 49) or placebo (n = 52) under double-blind conditions. Risperidone was superior to placebo in reducing serious behavioral problems. A standard 12-lead, electrocardiogram (ECG) was obtained in most subjects at screening and week 8. A pediatric electrophysiologist blind to treatment assignment reviewed all available ECGs for readability, abnormalities, and cardiac conduction parameters, including QTc. The electrophysiologist measurements were compared to machine readings. A second blinded electrophysiologist examined all available ECGs for abnormalities and a 20% random sample for QTc. Results: Of the 101 randomized subjects in the trial, complete pretreatment and week 8 data were available on 65 subjects (placebo n = 30; risperidone n = 35). The electrophysiologist did not identify any cardiac conduction adverse effects of risperidone and there was no difference in mean change on the QTc compared to placebo. The Bland-Altman plot showed a systematic bias in QTc measurements by the electrophysiologist and machine. Machine readings produced higher values than the electrophysiologist for shorter QTc intervals and machine scoring was lower than electrophysiologist readings for longer QTc values ( p = 0.001). Two electrophysiologists had overall percent agreements of 82.9% (95% CI: 76.3 to 89.6) on qualitative assessment and 88.6% (95% CI: 79.3 to 98.0) on QTc interval. Conclusion: Using conventional doses during acute treatment in children with ASD and serious behavioral problems, there was no difference in the mean change in QTc between risperidone and placebo. Compared to the electrophysiologist, the machine readings may miss elevated QTc measurements.

Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

“…We excluded 1127 records on the basis of titles and abstracts and retrieved 82 documents in full text: 47 studies have been excluded and 35 full-text articles included since satisfied the inclusion criteria. Reasons for the exclusion of the 46 papers: 27 studies whose comparator did not meet inclusion criteria, being augmentation trials without placebo arm or trials comparing two pharmacological interventions without placebo arm [52][53][54][55][56]; seven studies were pooled analyses or post-hoc analyses of randomized controlled trials [57][58][59][60][61][62][63]; nine studies whose design did not meet the inclusion criteria [64][65][66][67][68][69][70][71][72]; two studies for which we were not able to retrieve the full-text [73,74]; one study included only adults [75]. We retrieved 52 records from trial registers, 22 of which evaluated in full text: five trials were excluded since they did not show any result (clinicaltrials.gov identifiers: NCT00147394 [76], NCT00198107 [77], NCT00468130 [78], NCT01171937 [79], NCT00057408 [80]), four trials considered comparators that did not meet inclusion criteria (clinicaltrials.gov identifiers: NCT00080145 [81], NCT00205699 [82], NCT01333072 [83], NCT01844700 [84]), three trial whose design did not meet inclusion criteria (clinicaltrials.gov identifiers: NCT00166595 [85], NCT00691080 [86], NCT00619190 [87]), and two ongoing trials (clinicaltrials.gov identifiers: NCT02574741 [88], NCT03487770 [89]).…”

Segurança Da Risperidona Em Crianças E Adolescentes Com Transtorno Do Espectro Autista

“…Um estudo sobre os efeitos da risperidona na função cardíaca em crianças com TEA por oito semanas, não identificou nenhum evento adverso por condução cardíaca e não houve diferença na alteração média no intervalo QT em comparação ao placebo (53). Assim como não foram detectados eventos clinicamente significativos medidos por ECG (16), contudo, apesar disso, queixas de taquicardia foram relatadas por pacientes com TEA em tratamento com risperidona, mesmo sem alterações no ECG (18,54).…”