L Eugene Arnold1, Nicole Ober2, Michael G Aman1, Benjamin Handen2, Tristram Smith3, Xueliang Pan4, Susan L Hyman3, Jill Hollway1, Luc Lecavalier1, Kristin Page1, Robert Rice1. 1. 1 Nisonger Center UCEDD, The Ohio State University , Columbus, Ohio. 2. 2 Department of Psychiatry, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania. 3. 3 Department of Pediatrics, Division of Developmental and Behavioral Pediatrics, University of Rochester , Rochester, New York. 4. 4 Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University , Columbus, Ohio.
Abstract
OBJECTIVE: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial ofatomoxetine (ATX) and parent training (PT). METHODS: In a 2 × 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [≤1.8 mg/kg/d], and then maintained until week 10. Responders continued to week 34 or nonresponse. Placebo nonresponders had a 10-week ATX open trial; ATX nonresponders were treated clinically. All continued to week 34. With no further treatment from the study, all were invited to follow-up (FU) at 1.5 years postbaseline; 94 (73%) participated. Changes from Week 34 to FU and from baseline to FU were tested by one-way analysis of variance or chi-squared test. PT versus no PT was tested by chi-squared test, Fisher's exact test, Welch's t-test, Student's t-test, and Mann-Whitney's U test. RESULTS: For the whole sample, the primary outcomes (parent-rated ADHD on the Swanson, Nolan, and Pelham [SNAP] scale and noncompliance on the Home Situations Questionnaire [HSQ]) deteriorated mildly from week 34 to FU, but were still substantially better than baseline (SNAP: t = 12.177, df = 93, p < 0.001; HSQ: t = 8.999, df = 93, p < 0.001). On the SNAP, 61% improved ≥30% from baseline (67% did at week 34); on noncompliance, 56% improved ≥30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication. CONCLUSIONS: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).
RCT Entities:
OBJECTIVE: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial of atomoxetine (ATX) and parent training (PT). METHODS: In a 2 × 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [≤1.8 mg/kg/d], and then maintained until week 10. Responders continued to week 34 or nonresponse. Placebo nonresponders had a 10-week ATX open trial; ATX nonresponders were treated clinically. All continued to week 34. With no further treatment from the study, all were invited to follow-up (FU) at 1.5 years postbaseline; 94 (73%) participated. Changes from Week 34 to FU and from baseline to FU were tested by one-way analysis of variance or chi-squared test. PT versus no PT was tested by chi-squared test, Fisher's exact test, Welch's t-test, Student's t-test, and Mann-Whitney's U test. RESULTS: For the whole sample, the primary outcomes (parent-rated ADHD on the Swanson, Nolan, and Pelham [SNAP] scale and noncompliance on the Home Situations Questionnaire [HSQ]) deteriorated mildly from week 34 to FU, but were still substantially better than baseline (SNAP: t = 12.177, df = 93, p < 0.001; HSQ: t = 8.999, df = 93, p < 0.001). On the SNAP, 61% improved ≥30% from baseline (67% did at week 34); on noncompliance, 56% improved ≥30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication. CONCLUSIONS: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).
Entities:
Keywords:
ADHD; atomoxetine; autism spectrum disorder; follow-up studies; parent training
Authors: Benjamin L Handen; Michael G Aman; L Eugene Arnold; Susan L Hyman; Rameshwari V Tumuluru; Luc Lecavalier; Patricia Corbett-Dick; Xueliang Pan; Jill A Hollway; Kristin A Buchan-Page; Laura B Silverman; Nicole V Brown; Robert R Rice; Jessica Hellings; Daniel W Mruzek; Sarah McAuliffe-Bellin; Elizabeth A Hurt; Melissa M Ryan; Lynne Levato; Tristram Smith Journal: J Am Acad Child Adolesc Psychiatry Date: 2015-09-03 Impact factor: 8.829
Authors: Kenneth D Gadow; Nicole V Brown; L Eugene Arnold; Kristin A Buchan-Page; Oscar G Bukstein; Eric Butter; Cristan A Farmer; Robert L Findling; David J Kolko; Brooke S G Molina; Robert R Rice; Jayne Schneider; Michael G Aman Journal: J Am Acad Child Adolesc Psychiatry Date: 2016-04-13 Impact factor: 8.829
Authors: M Chowdhury; M G Aman; L Scahill; N Swiezy; L E Arnold; L Lecavalier; C Johnson; B Handen; K Stigler; K Bearss; D Sukhodolsky; C J McDougle Journal: J Intellect Disabil Res Date: 2010-03
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Authors: Brooke S G Molina; Stephen P Hinshaw; James M Swanson; L Eugene Arnold; Benedetto Vitiello; Peter S Jensen; Jeffery N Epstein; Betsy Hoza; Lily Hechtman; Howard B Abikoff; Glen R Elliott; Laurence L Greenhill; Jeffrey H Newcorn; Karen C Wells; Timothy Wigal; Robert D Gibbons; Kwan Hur; Patricia R Houck Journal: J Am Acad Child Adolesc Psychiatry Date: 2009-05 Impact factor: 8.829
Authors: Laura Silverman; Jill A Hollway; Tristram Smith; Michael G Aman; L Eugene Arnold; Xueliang Pan; Xiaobai Li; Benjamin L Handen Journal: Res Autism Spectr Disord Date: 2014-07-01
Authors: Karen Bearss; Cynthia Johnson; Tristram Smith; Luc Lecavalier; Naomi Swiezy; Michael Aman; David B McAdam; Eric Butter; Charmaine Stillitano; Noha Minshawi; Denis G Sukhodolsky; Daniel W Mruzek; Kylan Turner; Tiffany Neal; Victoria Hallett; James A Mulick; Bryson Green; Benjamin Handen; Yanhong Deng; James Dziura; Lawrence Scahill Journal: JAMA Date: 2015-04-21 Impact factor: 157.335