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A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

Neuropsychopharmacologyvolume 43pages17721778 (2018) | Download Citation


In a prior report, we showed that extended-release guanfacine (GEXR) is safe and effective for children with autism spectrum disorder (ASD) accompanied by ADHD symptoms. Here, we examine the impact of GEXR on oppositional behavior, anxiety, repetitive behavior, and sleep disturbance. Sixty-two subjects with ASD (53 boys, 9 girls; ages 5–14 years) were randomly assigned to GEXR (n = 30) or placebo (n = 32) for 8 weeks. Outcomes include the Home Situation Questionnaire-Modified for ASD (HSQ-ASD), Anxiety scale of the Child and Adolescent Symptom Inventory (CASI), Children’s Yale-Brown Obsessive-Compulsive Scale-Modified for ASD (CYBOCS-ASD), and Children’s Sleep Habits Questionnaire (CSHQ). A repeated measures linear mixed model was used to determine the effects of treatment group and time on HSQ scores. For other measures, change from baseline was evaluated with Analysis of Covariance (ANCOVA).

After 8 weeks of treatment, parent ratings of oppositional behavior on the HSQ declined by 44% (per item mean from 3.4 to 1.9) in the GEXR group compared to 12% (from 3.3 to 2.9) for placebo (p = 0.004). Repetitive behavior on the CYBOCS-ASD showed a significantly greater decline in GEXR-treated participants compared to placebo (24% vs. <1%, p = 0.01). No group differences were observed on CASI Anxiety or CSHQ (p = 0.64 and 0.75, respectively). GEXR was effective in reducing oppositional behavior and, more modestly, repetitive behavior. GEXR was not superior to placebo for anxiety, though baseline anxiety ratings were low. GEXR did not significantly improve sleep habits. Future studies could focus on repetitive behavior or anxiety, symptoms with limited treatment options.

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The authors thank Courtney McCracken for her assistance with data analysis for this study.


The study was supported by NIMH grants to Dr. Scahill (R01MH083707), Dr. McDougle (RO1MH83739), Dr. McCracken (RO1MH083747), and Dr. King (R01MH86927); by a Yale Clinical and Transitional Science Award (UL1 RR024139) from the NIH National Center for Research Resources; and by Atlanta Clinical and Translational Science Institute, Emory University, which is supported by the NIH National Center for Advancing Translational Sciences under award UL1TR000454. Shire Pharmaceuticals provided active extended-release guanfacine and placebo. Dr. LCP receives research support from a Career Development Award with the North Carolina Translational and Clinical Sciences Institute, which is supported by NIH National Center for Advancing Translational Sciences under award UL1TR001111. Dr. LCP has received study drug from Nutramax, Inc. Dr. LS has served as a consultant for Bracket, Roche, and Shire, and he has served on the speaker’s bureau for the Tourette Syndrome Association. Dr. JTM has served as a consultant for Dart Neuroscience and Roche; he has received research support from Roche; he has received study drug and matching placebo from Shire; and he has served on the speaker’s bureau for the Tourette Syndrome Association. Dr. BK has received research support from Roche and Seaside Therapeutics.

Author information


  1. Department of Psychiatry, Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, 101 Renee Lynne Court, Carrboro, NC, 27510, USA

    • Laura C. Politte
  2. Department of Pediatrics, Marcus Autism Center, Emory University School of Medicine, Atlanta, USA

    • Lawrence Scahill
  3. Department of Pediatrics, Pediatrics Biostatistics Core, Emory University School of Medicine, Atlanta, USA

    • Janet Figueroa
  4. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, USA

    • James T. McCracken
  5. Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco School of Medicine, San Francisco, USA

    • Bryan King
  6. Department of Psychiatry, Lurie Center for Autism, Harvard Medical School, Boston, USA

    • Christopher J. McDougle


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The authors declare that they have no conflict of interest.

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Correspondence to Laura C. Politte.

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