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A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder


Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12–25 years. All participants tolerated riluzole 200 mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale. The results of this trial indicate that 5-week of riluzole treatment was well tolerated, but had no significant effect on the target symptoms. Trial Registration Identifier NCT02081027, Registered 5 August 2013, First participant enrolled 19 September 2013.

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The authors would like to acknowledge the contributions of Kaela O’Brien and Bridget Crippen for their assistance with study coordination and data collection.


This study was funded by the Center for Clinical and Translational Science and Training at the University of Cincinnati via an Institutional Clinical and Translational Science Award, NIH/NCRR Grant No. 8UL1TR000077-04.

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Authors and Affiliations



LKW participated in study design, study execution, and drafted the manuscript. RA and PH completed the statistical analysis and assisted with drafting the statistical portion of the manuscript. CT and APB completed the ERK biomarker analysis. MH drafted the ERK analysis portion of the manuscript. RCS and EVP assisted in study execution, assisted in drafting the manuscript and reviewed the data analysis. CAE participated in study design, study execution, and oversaw manuscript development. All authors read, edited, and approved the final manuscript.

Corresponding author

Correspondence to Logan K. Wink.

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Conflict of interest

The authors declare that they have no interests that compete directly with this work, though LKW, CRT, RSC, EVP, and CAE do receive research support from various sources for other work. LKW’s current and/or past research is supported by the Simons Research Foundation, Autism Speaks, Riovant Sciences Ltd, and Cures Within Reach. Dr. Wink is currently a NICHM-NIMH supported T32 fellow. She is an inventor on intellectual property held by Cincinnati Children’s Hospital Research Foundation for a treatment in autism spectrum disorder. LKW has also served as a past consultant for Otsuka and Ovid. CRT has been a past one-time consultant for Confluence Pharmaceuticals. His current and/or past research has been supported by the National Institute of Mental Health and Indiana University School of Medicine. RCS receives research support from the Rubenstein foundation. EVP receives research support from Cincinnati Children’s Hospital Research Foundation and the National Institutes of Health. CAE has received current and/or past research support from the National Institutes of Health, the United States Department of Defense, the United States Centers for Disease Control, the John Merck Fund, Autism Speaks, the Simons Foundation, Cincinnati Children’s Hospital Research Foundation, the FRAXA Research Foundation, the National Fragile X Foundation, the Roche Group, Seaside Therapeutics, Novartis, Neuren, Alcobra, and Indiana University School of Medicine. He is a past consultant to Alcobra, the Roche Group, and Novartis. He is a current consultant to Fulcrum Therapeutics. He holds equity interest in and is a consultant for Confluence Pharmaceuticals. He is the inventor on intellectual property held by Cincinnati Children’s Hospital Research Foundation and Indiana University describing methods for diagnosis and treatment methods in autism spectrum disorder and fragile X syndrome. RA, PH, APB, and MH have no conflicts to report.

Ethical Approval

This study was approved by the Cincinnati Children’s Hospital institutional review board. All procedures performed in this study were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Guardians of all participants provided written informed consent prior to participation.

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Wink, L.K., Adams, R., Horn, P.S. et al. A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder. J Autism Dev Disord 48, 3051–3060 (2018).

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  • Autism
  • Autism spectrum disorder
  • Riluzole
  • Irritability
  • Extracellular signal related kinase
  • ERK