Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

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• 作者：Diane C. Chugani ; PhD¹ ; ² ; ^{Diane.Chugani@nemours.org" class="auth_mail" title="E-mail the corresponding author} ; Harry T. Chugani ; MD¹ ; ² ; ³ ; Max Wiznitzer ; MD⁴ ; Sumit Parikh ; MD⁵ ; Patricia A. Evans ; MD ; PhD⁶ ; Robin L. Hansen ; MD⁷ ; Ruth Nass ; MD⁸ ; ⁹ ; James J. Janisse ; PhD¹⁰ ; Pamela Dixon-Thomas ; PhD¹ ; Michael Behen ; PhD¹ ; ² ; Robert Rothermel ; PhD¹¹ ; Jacqueline S. Parker ; BSc¹ ; ² ; Ajay Kumar ; MD ; PhD¹ ; ² ; ³ ; ¹² ; Otto Muzik ; PhD¹ ; ² ; ³ ; ¹² ; David J. Edwards ; PharmD¹³ ; Deborah Hirtz ; MD¹⁴ ; on behalf of the Autism Center of Excellence Network^&lowast ; ; Huiyuan Jiang ; MD ; Lalitha Sivaswamy ; MD ; Ginger Steinhilber ; RN ; Kristin Kennedy ; RN ; Kathy Pawlik ; CNP ; Ruth Roeder ; PNP ; Monica Malian ; Hailey Turner ; Amira Hanna ; Jamie Katusin ; Deanna Supula ; RN ; Stacey Halverson ; William Guy ; Nore Gjolaj ; Thomas Mangner ; PhD ; Pulak Chakraborty ; PhD ; Angela Wigeluk ; Gregory Patterson ; Andrew Mosqueda ; Melissa Burkett ; Anna DeBoard ; RN ; Jane Cornett ; RN ; Mei-li Lee ; Xin Lu ; Catherine Germain ; Marianne Majkowski ; DO ; Beth French ; PNP ; Amy Stolinski ; Suzi Naguib ; PhD ; Courtney Wolfe-Christensen ; PhD ; Sara Taylor ; Jamal Ameli ; Julie Kemp McQueeney ; Michelle Rubinlicht ; Bethany Gorka ; Erin Zacharski ; Jeffrey L. Blumer ; PhD ; MD ; Kathleen Maxwell ; RN ; Catherine Tasi ; RN ; Philip Toltzis ; MD ; Jolee Kalic ; RN ; Dianne Morus ; RRT ; Jany Paulett ; Bonnie Rosolowski ; RRT ; Michael Banchy ; RPh ; Kathryn Westlake ; RPh ; Barbara Calabro ; CCRP ; Carol Tacket ; CCRP ; Ina Adkins ; RN ; Kenneth Buchheit ; RN ; Kathryn Hepper ; RN ; David Speicher ; MD ; Susan Bergant ; RN ; Jennifer Haky ; Mary Beth Frohnapfel ; RN ; Cindy Schaefer ; RN ; Allison Browning ; Roberta Bauer ; MD ; Rebecca Embacher ; Julie Knapp ; PhD ; Stephanie Levy ; Diane Davies ; Donna Lach ; John Petrich ; Rph ; MS ; Sharon Kreischer ; Patty Blubaugh ; Mary Ann Morris ; Carolyn Garver ; Mariam Andersen ; Meredith Greene ; Amanda Richards ; Maria Rocha ; Ruth Merryman ; Sailaja Golla ; MD ; Alan Lorenzen ; Julie Long Sherrod ; Paulette Perryman ; Kara Lorduy ; Kathleen Angkustsiri ; MD ; Lauren Back Plumer ; MD ; Mary Jacena Siy Leigh ; MD ; Susan C. Bacalman ; MSW ; MD ; Dorcas Liriano Roa ; PhD ; Kushma Govindappa ; MD ; Gayatri Mahajan ; MD ; Erika Bickel ; Norman Brule ; Emma Hare ; Nadir Sarwary ; Dominique Cargill ; Joyce Lee ; Smiley Hom ; Dennis Steindorf ; Mandy Pietrykowski ; Kindra Root ; Sarah Coffey ; Elise Phelps Hanzel ; PhD ; Adriana Santana ; Clara Ramirez ; Stefanie Berci ; Nielsen Gabriel ; Glenn Hirsch ; MD ; Elizabeth Roberts ; PsyD ; Amanda Zwilling ; Resham Gellatly ; Dana Levy ; PsyD ; Sandi Lee ; RPh ; Jennifer Rodman ; Amira Hanna ; Nora Oberfield ; Susan Friedland ; Catherine Lord ; PhD ; Rene Kozloff ; RN ; PhD ; Celeste Crouse ; Stephanie Millen ; Alex J. Co&iacute ; mbre ; BA ; MPS ; CCRA ; Kelly L. McCarter ; MA ; LPC MHSP ; David Posey ; MD
• 关键词：1-PP ; 1-pyrimidylpiperazine ; ABC ; Aberrant Behavior Checklist ; ADI-R ; Autism Diagnostic Interview-Revised ; ADOS ; Autism Diagnostic Observation Schedule ; ADOS-CTS ; Autism Diagnostic Observation Schedule Composite Total Score ; ADOS-RRB ; ADOS Restricted and Repetitive Behavior ; ADOS-SA ; Autism Diagnostic Observation Schedule Social Affect ; AMT ; α[11C]methyl-L-tryptophan ; ASD ; Autism spectrum disorder ; PET ; Positron emission tomography ; RBS ; Repetitive Behaviors Scale-Revised ; SUV ; Standard uptake v
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：170
• 期：Complete
• 页码：45-53.e4
• 全文大小：1085 K

文摘

To determine safety and efficacy of the 5HT_1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD).

d="absSec_2">Study design

d="abspara0015">Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy.

d="absSec_3">Results

d="abspara0020">There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups.

d="absSec_4">Conclusions

d="abspara0025">Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions.

d="absSec_5">Trial registration

d="abspara0030">d="intref0015" class="interref" data-locatorType="url" data-locatorKey="http://ClinicalTrials.gov">ClinicalTrials.gov: d="intref0020" class="interref" data-locatorType="ctgov" data-locatorKey="NCT00873509">NCT00873509.