The effects of aripiprazole on electrocardiography in children with pervasive developmental disorders.
ABSTRACT 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.
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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. Copyright © 2013 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 05/2013; 28(3). DOI:10.1002/hup.2309 · 1.85 Impact Factor
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ABSTRACT: Bipolar disorder is a pernicious illness. Compared with the later-onset form, early onset bipolar disorder is associated with worse psychosocial outcomes, and is characterized by rapid cycling and increased risks of substance abuse and suicide attempts. Controlling mood episodes and preventing relapse in this group of pediatric patients requires careful treatment. Here, we review the effectiveness of aripiprazole for bipolar disorder in children and adolescents, with discussion of this drug's unique pharmacological profile and various clinical study outcomes. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used in children and adolescents, as it is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. The presently reviewed randomized controlled trials (RCTs) and non-RCTs generally reported aripiprazole to be effective and well-tolerated in children and adolescents with bipolar disorder. However, due to the limited number of RCTs, the present conclusions must be evaluated cautiously. Furthermore, aripiprazole cannot yet be considered a preferred treatment for children and adolescents with bipolar disorder, as there is not yet evidence that aripiprazole shows greater efficacy compared to other second-generation antipsychotics. Additional data are needed from future head-to-head comparison studies.Adolescent Health, Medicine and Therapeutics 01/2014; 5:211-221. DOI:10.2147/AHMT.S50015
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ABSTRACT: Learning Objectives: After participating in this educational activity, the physician should be better able to1. Prescribe the appropriate psychotropic medication to treat symptoms of ASD.2. Identify the side effects of the psychotropic medications used to treat ASD.Autism spectrum disorders (ASDs) are characterized by core deficits in social communication and language, and restrictive and repetitive behaviors that cause significant functional impairment and distress for affected individuals and their caregivers. The increasing prevalence of ASD, most recently estimated as 1 in 88 children, presents an ever-increasing burden on families, schools, medical systems, and society at large. Individuals with ASD commonly present for treatment of associated emotional and behavioral disturbances that include anxiety, symptoms of ADHD, compulsions and other repetitive behaviors, mood lability, irritability, aggression, and sleep disturbance. Psychotropic medications are widely utilized in alleviating these symptoms, though rigorous clinical trials in ASD are lacking for most areas of impairment. Strong evidence from randomized, placebo-controlled trials supports the use of atypical antipsychotics, particularly risperidone and aripiprazole, for managing severe irritability and aggression in ASD. Serotonin reuptake inhibitors are commonly used to treat anxiety and compulsions, though reports of efficacy in the literature are mixed, and behavioral side effects in children are common. Minimal evidence supports the utility of anticonvulsants and traditional mood stabilizers in managing mood lability and aggression. Stimulant and nonstimulant ADHD medications can be effective for reducing hyperactivity, inattention, and impulsivity, though to a lesser degree than in ADHD populations without ASD and with greater risk of adverse effects. Psychopharmacological interventions in development for core symptoms of autism include those that target the glutamatergic and GABAergic neurotransmitter systems and the neuropeptide oxytocin. Further research is needed to establish evidence-based interventions in ASD populations.Harvard Review of Psychiatry 01/2014; 22(2):76-92. DOI:10.1097/HRP.0000000000000030 · 2.49 Impact Factor