QTc Changes after 6 Months of Second-Generation Antipsychotic Treatment in Children and Adolescents

Castro, Elena; Fraguas, David; Laita, P.; Moreno, Dolores; Parellada, Mara; Pascual, David W.; Álvarez, Mar; Merchán-Naranjo, Jessica; Rapado, Marta; Giráldez, Marisa; Leiva, Marta; Arango, Celso

doi:10.1089/cap.2007.0115

Cited by 14 publications

(5 citation statements)

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“…While no other medication carries FDA approval in ASD, several others have been shown to improve irritability when used either as monotherapy or adjunctively (Ghanizadeh and Moghimi-Sarani, 2013; Gordon et al, 1993; Jaselskis et al, 1992; Posey et al, 2004). However, all of these pharmacological interventions carry a risk of adverse events, and in the case of risperidone and aripiprazole, serious health complications (Correll and Carlson, 2006; Correll et al, 2006; De Castro et al, 2008; Roke et al, 2009; Safer, 2004). This profile has led to the extensive monitoring of patients on second-generation antipsychotics with baseline, quarterly, semi-annual, and annual lab tests, which are often difficult for children with ASD.…”

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confidence: 99%

Lagging skills contribute to challenging behaviors in children with autism spectrum disorder without intellectual disability

Maddox

Cleary

Kuschner

et al. 2017

Autism

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Many children with autism spectrum disorder display challenging behaviors. These behaviors are not limited to those with cognitive and/or language impairments. The Collaborative and Proactive Solutions framework proposes that challenging behaviors result from an incompatibility between environmental demands and a child's "lagging skills." The primary Collaborative and Proactive Solutions lagging skills-executive function, emotion regulation, language, and social skills-are often areas of weakness for individuals with autism spectrum disorder. The purpose of this study was to evaluate whether these lagging skills are associated with challenging behaviors in youth with autism spectrum disorder without intellectual disability. Parents of 182 youth with autism spectrum disorder (6-15 years) completed measures of their children's challenging behaviors, executive function, language, emotion regulation, and social skills. We tested whether the Collaborative and Proactive Solutions lagging skills predicted challenging behaviors using multiple linear regression. The Collaborative and Proactive Solutions lagging skills explained significant variance in participants' challenging behaviors. The Depression (emotion regulation), Inhibit (executive function), and Sameness (executive function) scales emerged as significant predictors. Impairments in emotion regulation and executive function may contribute substantially to aggressive and oppositional behaviors in school-age youth with autism spectrum disorder without intellectual disability. Treatment for challenging behaviors in this group may consider targeting the incompatibility between environmental demands and a child's lagging skills.

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confidence: 99%

Lagging skills contribute to challenging behaviors in children with autism spectrum disorder without intellectual disability

Maddox

Cleary

Kuschner

et al. 2017

Autism

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“…Furthermore, previously reported QTc prolongation (defined as incidence of QTc > 450 msec or >460 msec) in youth receiving ziprasidone in the aforementioned studies have ranged from 0% (i.e., 0/12 (3) and 0/21) (22) to 15.0% (i.e., 3/20) (21), which was lower than our rate of 24.1%. For additional comparison, 6 months of treatment of 38 children and adolescents (mean age: 15.1 (4–18) years, 68.4% male, 92.1% Caucasian) with risperidone (N=12, mean dose: 2.4 (0.4–5) mg), olanzapine (N=8, mean dose: 10.9 (5–25) mg) or quetiapine (N=18, mean dose 469 (100–1500) mg) was associated with a mean QTc prolongation of 6.3±25.5 msec (range: −38.0 to +70.0 msec) for the combined group (8). However, although based on the reported range, at least, one patient treated with a second-generation antipsychotic other than ziprasidone had a QTc prolongation of more than 60 msec compared to baseline, the authors did not report the percent of patients with newly emerging QTc abnormalities, precluding a comparison with our ziprasidone treated pediatric sample.…”

Section: Discussionmentioning

confidence: 99%

“…However, ziprasidone has the potential to prolong the rate-corrected QT interval (QTc) in the electrocardiogram. This effect is greater than the QTc prolongation observed during treatment with haloperidol, risperidone, olanzapine and quetiapine (7,8). Significant prolongation of QTc is generally considered a risk factor for torsades de pointes (TdP), ventricular fibrillation and sudden death, particularly when the QTc is greater than 500 msec (9–11).…”

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confidence: 85%

QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Correll¹,

Lops²,

Figen³

et al. 2011

J. Clin. Psychiatry

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Objective To assess the incidence of symptoms (palpitations, syncope) and electrocardiographic signs (increased QT duration and dispersion) of an increased risk of torsades de pointes in youth treated with ziprasidone. Method Prospective, observational study of 29 youth (15.3±2.9 years) receiving ziprasidone (112.8±50.6 mg/day, range: 20–240mg/day) for 99.3±108.7 days. All patients had normal electrocardiograms (EKGs) and no serious medical illness at baseline. Patients had a mean of 2.7±1.3 (median=3, range: 1–7, total: 49) follow-up EKGs performed monthly for 3 months and every three months thereafter, with concurrent ziprasidone blood level measurements. Heart rate-corrected QT (QTc) duration and dispersion were measured manually in ≥6 EKG leads. QTc interval > 450msec or ≥60msec increase, and QTc dispersion >100msec were considered abnormal. Results No patient reported syncope or symptomatic arrhythmias. Seven patients (24.1%) developed EKG abnormalities; 5 had peak QTc durations >450msec and 2 had peak QTc dispersion >100 msec. The baseline-to-peak QTc duration increased by 22.9±21msec (p<0.0001). The baseline-to-peak QTc dispersion increased by 6.1±31.4msec (p=0.30). The peak QTc duration and dispersion occurred after 47.6±45.2 and 60.4±72.1 treatment days, respectively. Baseline-to-peak QTc duration and dispersion changes were not correlated with ziprasidone dose (p=0.67) or plasma levels (p=0.37). Conclusions Ziprasidone was associated with a dose- and level-independent, significant prolongation of QTc duration in one quarter of youth. However, prolongation of QTc dispersion was non-significant, and no patient experienced concomitant abnormal prolongation of both QTc duration and QTc dispersion. The dissociation between prolonged QTc duration and dispersion suggests low arrhythmogenic potential in youth with normal baseline EKGs.

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“…Data on children and adolescents are very limited. De Castro and colleagues (2008) who examined QTc interval in 38 young patients (aged 4–18 years) before and after they had been treated with risperidone, olanzapine and quetiapine over a six-month period, could not identify any cardiovascular changes. Data on short-term adverse effects of ziprasidone are available from one eight-week RCT in children with Tourette’s syndrome (Sallee et al, 2000).…”

Section: Cardiovascular Safetymentioning

confidence: 99%

Antipsychotics use in children and adolescents: An on-going challenge in clinical practice

et al. 2014

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Antipsychotic medications (APs) are a well-established pharmacological treatment in adults with serious mental health problems. However, many adult mental health disorders have their origins and onset in childhood or adolescence. The understanding that neuropsychiatric conditions of childhood are in part biologically determined, led to an increase in the number of clinical trials supporting evidence on the efficacy of antipsychotic agents as first-line treatment for childhood psychotic disorders and therapeutic augmentation of nonpsychotic conditions. In recent years the use of antipsychotics in children and adolescents for neurodevelopmental, behavioural and psychiatric disorders has significantly increased while the age of prescription has decreased. These trends have not been matched by advances in the understanding of APs' safety profile in this group of patients. It is therefore crucial that current and future practice is informed by up-to-date synthesis of the evidence and clinical guidelines about the use and monitoring of these treatments in paediatric populations, since the effectiveness of early therapeutic interventions in children can affect positively the long-term outcome.

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QTc Changes after 6 Months of Second-Generation Antipsychotic Treatment in Children and Adolescents

Cited by 14 publications

References 10 publications

Lagging skills contribute to challenging behaviors in children with autism spectrum disorder without intellectual disability

Lagging skills contribute to challenging behaviors in children with autism spectrum disorder without intellectual disability

QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Antipsychotics use in children and adolescents: An on-going challenge in clinical practice

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