The Effects of Aripiprazole on Electrocardiography in Children with Pervasive Developmental Disorders

Section of Pediatric Cardiology, Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana 46202-5200, USA.
Journal of child and adolescent psychopharmacology (Impact Factor: 2.93). 07/2012; 22(4):277-83. DOI: 10.1089/cap.2011.0129
Source: PubMed


Psychotropic medications, including the atypical antipsychotics, have historically been scrutinized for cardiac effects and risk of sudden death. Aripiprazole is an atypical antipsychotic approved for pediatric use in schizophrenia, bipolar I disorder, and autistic disorder. Adult studies have evaluated aripiprazole's effects on electrocardiograms, but no pediatric studies have been published to date.
Electrocardiographic data were collected from children and adolescents participating in a 14-week, prospective, open-label study (n=25) of aripiprazole for irritability in pervasive developmental disorder not otherwise specified and Asperger's disorder. A 12-lead electrocardiogram was obtained at the baseline and end point visits. The electrocardiograms were evaluated for abnormal findings, and the PR, QRS, QT(c), and RR intervals were recorded. The QT interval was corrected using Bazett's, United States Food and Drug Administration (FDA) Pharmacology Division, and Fridericia's formulas.
Twenty-four subjects received both baseline and posttreatment electrocardiograms. The mean age was 8.6 years (range 5-17 years). The average final aripiprazole dose was 7.8 mg/day (range 2.5-15 mg/day). There were no significant differences noted with the PR, QRS, RR, and QT(c) intervals after aripiprazole therapy. Also, there was no significant correlation between the dose given and the percent change in the QT(c). No post-treatment QT(c) exceeded 440 ms.
To our knowledge, this is the first systematic evaluation of the cardiac effects of aripiprazole in children and adolescents. The results are consistent with previously published literature in adults that aripiprazole has no significant cardiac effects and can be deemed a low risk for causing sudden death. It will be important to confirm these findings in a randomized controlled trial.

17 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale Autism and related pervasive developmental disorders (PDD) are characterized by impairments in social interaction and communication, restricted interests, and repetitive and stereotyped patterns of behavior. Individuals with PDD frequently display irritability and disruptive behaviors including tantrums, self-injurious behavior, and aggression. Atypical antipsychotics are currently the most efficacious pharmacological interventions available for treatment of irritability associated with PDD. Objectives This article aims to review the body of literature pertaining to the use of atypical antipsychotics in the treatment of patients with PDD. Methods A PubMed literature search was conducted using the following key words: autism, pervasive developmental disorders, atypical antipsychotics, risperidone, aripiprazole, quetiapine, ziprasidone, olanzapine, clozapine, paliperidone, iloperidone, asenapine, and lurasidone. Search terms were limited to English language, human subjects, and publication from 1999 to present. Relevant references from identified articles were also reviewed. Results The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi-site, randomized, controlled trials. Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings, though newer agents such as ziprasidone and paliperidone show promise. Conclusions Atypical antipsychotics are currently first-line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD. Further placebo-controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications. There is also a need for the development of novel, targeted drugs with more favorable long-term side effect profiles.
    Psychopharmacology 04/2013; 231(6). DOI:10.1007/s00213-013-3068-y · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia. Methods: Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula. Results: The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007). Conclusion: To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval.
    Human Psychopharmacology Clinical and Experimental 05/2013; 28(3). DOI:10.1002/hup.2309 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atypical antipsychotics (AP) are increasingly being used in children and adolescents for the treatment of psychiatric disorders. Atypical AP may cause QT prolongation on the electrocardiogram (ECG), which predisposes patients to an increased risk of developing threatening ventricular arrhythmias. Although this phenomenon has been exhaustively reported in adults, few studies investigated the safety of these drugs in pediatric patients. We performed an open-label, prospective study to assess the arrhythmic risk of aripiprazole and risperidone in a pediatric population. A total of 60 patients (55M/5F, mean age 10,2+2,6years, range 4-15years), receiving a new prescription of aripiprazole or risperidone in monotherapy underwent a standard ECG before and after two months from the beginning of antipsychotic treatment. Basal and post-treatment ECG parameters, including mean QT (QTc) and QT dispersion (QTd) , were compared within treatment groups. Twenty-nine patients were treated with aripiprazole (mean dosage 7.4+3,1mg/day) and 31 with risperidone (mean dosage 1,5+1mg/day). In our series, no patient exhibited pathological values of QTc or QTd before and after treatment for both drugs. However, treatment with risperidone was associated with a slight increase of both mean QTc and QTd values (407,4+11,9ms vs 411,2+13,0ms, p<0.05; and 40,0+4,4ms vs 44,7+5,5ms, p<0.001, respectively). Treatment with aripiprazole was associated with no changes of mean QTc, even if a small increase of QTd, (40,6+6,5ms vs 46,3+7,2ms, p<0.01) was observed. Although our data suggest a slight effect of aripiprazole and risperidone on ventricular repolarization, it is unlikely that such a change results in clinically relevant effects. The treatment with risperidone and aripiprazole in children with psychiatric disorders is not associated with clinically relevant modifications of QT interval. Caution in prescribing these drugs, however, is necessary in patients with family history of a genetic predisposititon to arrhythmias in order to warrant a reliable assessment of drug-induced QT prolongation.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2013; 51. DOI:10.1016/j.pnpbp.2013.10.020 · 3.69 Impact Factor
Show more

Similar Publications