Dataset Information

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

ABSTRACT: We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n?=?45) or aripiprazole (n?=?47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8. Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8. All patients randomized to aripiprazole completed the study, and no serious adverse events were reported. Three patients in placebo group discontinued. Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents.

SUBMITTER: Ichikawa H

PROVIDER: S-EPMC5617873 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

Ichikawa Hironobu H Mikami Katsunaka K Okada Takashi T Yamashita Yushiro Y Ishizaki Yuko Y Tomoda Akemi A Ono Hiroaki H Usuki Chiharu C Tadori Yoshihiro Y

Child psychiatry and human development 20171001 5

We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n = 45) or aripiprazole (n = 47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist ...[more]

PMID: 28004215

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Project description:This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Clinical trial registration information: Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https://clinicaltrials.gov ; NCT01302964.

Project description:Aripiprazole modulates dopaminergic and serotonergic pathways that may play a role in the pathogenesis of Tourette's disorder (TD). This trial evaluated the efficacy and safety of oral aripiprazole in the suppression of tics in children and adolescents with TD.This phase 3, randomized, double-blind, placebo-controlled trial ( ClinicalTrials.gov , NCT01727700) recruited patients who were 7-17 years old with a diagnosis of TD from hospitals, private practices, and research clinics at 76 sites in the United States, Canada, Hungary, and Italy. Patients were randomized in a 1:1:1 ratio by using an interactive voice/web-response system to low-dose aripiprazole (5?mg/day if <50?kg; 10?mg/day if ?50?kg), high-dose aripiprazole (10?mg/day if <50?kg; 20?mg/day if ?50?kg), or placebo for 8 weeks. Randomization was stratified by region (North America or Europe) and baseline body weight (<50?kg vs. ?50?kg). The primary efficacy endpoint was mean change from baseline to week 8 in the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) for the intent-to-treat population.Between November 2012 and May 2013, 133 patients were recruited and randomized to low-dose aripiprazole (n?=?44), high-dose aripiprazole (n?=?45), or placebo (n?=?44). Least-squares mean treatment differences versus placebo in change from baseline to week 8 in the YGTSS-TTS were statistically significant (high dose, -9.9 [95% confidence interval, CI, -13.8 to -5.9], low dose, -6.3 [95% CI, -10.2 to -2.3]). At week 8, 69% (29/42) of patients in the low-dose and 74% (26/35) of patients in the high-dose aripiprazole groups demonstrated a Clinical Global Impression-Tourette's Syndrome improvement score of 1 (very much improved) or 2 (much improved) compared with 38% (16/42) in the placebo group. The most common adverse events (AEs) were sedation (low dose, 8/44 [18.2%], high dose, 4/45 [8.9%], placebo, 1/44 [2.3%]), somnolence (low dose, 5/44 [11.4%], high dose, 7/45 [15.6%], placebo, 1/44 [2.3%]), and fatigue (low dose, 3/44 [6.8%], high dose, 7/45 [15.6%], placebo, 0). No serious AEs or deaths occurred.This study indicates that oral aripiprazole is a safe and effective treatment for tics in children and adolescents with TD.

Project description:OBJECTIVES:Our clinical experience with low dose loxapine (5-15?mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. METHODS:We performed a 12 week open trial of add-on loxapine in subjects, ages 13-65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15?mg daily, starting with 5?mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. RESULTS:Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13-39). Median final loxapine dose was 7.5?mg/day (2.5-15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was -31%, p=0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p=0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly (p=0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype. CONCLUSIONS:Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study.

Dataset Information

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

Publications

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

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