A Randomized Controlled Trial of Riluzole in Autism Spectrum Disorder

Thursday, May 11, 2017: 2:40 PM
Yerba Buena 3-6 (Marriott Marquis Hotel)
R. Nicolson1, T. Bennett2, O. Akintan3, C. Harvey4, J. A. Brian5, L. Capano6, C. Hodgins7, O. Kraus de Camargo3, D. Mankad8, A. Ahmad7, M. Chalupka9, L. Colli10, L. Genore8, A. Greco9, T. Lui11, A. Iaboni8, I. O'Connor12, D. Odrobina8, K. Thorpe13 and E. Anagnostou14, (1)University of Western Ontario, London, ON, CANADA, (2)Offord Centre for Child Studies, McMaster University, Hamilton, ON, CANADA, (3)McMaster University, Hamilton, ON, Canada, (4)University of Western Ontario, London, ON, Canada, (5)Bloorview Research Institute, Toronto, ON, Canada, (6)Autism Research Centre, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada, (7)Lawson Health Research Institute, London, ON, Canada, (8)Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada, (9)McMaster University, Hamilton, ON, CANADA, (10)Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, ON, CANADA, (11)Holland Bloorview, Toronto, ON, CANADA, (12)McMaster Universtiy-Offord Centre, Dundas, ON, CANADA, (13)University of Toronto, Toronto, ON, Canada, (14)HOlland Bloroview Kids Rehab hospita;, University of Toronto, Toronto, ON, Canada
Background: Medications currently indicated for children and adolescents with Autism Spectrum Disorder (ASD) are used to treat interfering behaviours often seen in ASD, but there are no medications with evidence supporting their use to treat the core symptoms of the disorder. Convergent evidence, however, suggests that ASD is associated with a shift in balance of neural excitation to inhibition. Riluzole is a glutamatergic modulator with neuroprotective and plasticity-enhancing properties, suggesting that it may play an important role in the treatment of neurodevelopmental disorders.

Objectives: The primary aim of this study was to investigate the safety and efficacy of riluzole in treating the core symptom domains in ASD. The effect of riluzole on interfering behaviours seen in children and adolescents with ASD was also examined.

Methods: 58 children and adolescents (mean age: 11.5±3.0 years) participated in a 12 week, randomized, double-blind, placebo-controlled trial of riluzole. Riluzole was started at 50mg daily and, for subjects 12 years of age and older, was increased after two weeks to 50mg twice daily. The primary outcome measure was the Aberrant Behaviour Scale – Social Withdrawal subscale [ABC-SW] score). Repetitive and ritualistic behaviors were evaluated by the Yale-Brown Obsessive-Compulsive Scale [YBOCS] total score, and the Repetitive Behaviour Scale [RBS] total score. Adverse effects were also assessed every two weeks using the Safety Monitoring Uniform Research Form (SMURF). Irritability, hyperactivity, and anxiety, common interfering behaviours in ASD, were evaluated using the relevant ABC subscales and the Spence Children’s Anxiety Scale.

Results: 54 patients completed the trial. Four patients withdrew from the trial (two from each group), two due to adverse events and two due to the withdrawal of consent. Riluzole was well tolerated, with no serious adverse reactions reported. There were no significant differences between participants on placebo and those on riluzole with regards to social withdrawal, repetitive behaviour, or ritualistic behaviour (ABC-SW: p=0.3; YBOCS: p=0.1; RBS: p=0.1). However, subjects taking riluzole did have a significantly greater and clinically meaningful reduction in their scores on the ABC-Irritability (p=0.03) and ABC-Hyperactivity (p=0.03) subscales. None of the other outcome variables showed significant group differences.

Conclusions: Although riluzole was generally well-tolerated, it was not superior to placebo in terms of reduction in the core symptom domains of ASD. However, patients taking riluzole did show a significantly greater reduction in hyperactivity and irritability, both of which are interfering symptoms commonly associated with ASD.