A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.
OBJECTIVE
Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder.


METHODS
This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed.


RESULTS
A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups.


CONCLUSIONS
This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.
1 IMPACT Strategic Research Centre (Barwon Health), Deakin University, Geelong, VIC, Australia.|2 Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.|3 The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
Olivia M
OM
Dean
4 Centre for Developmental Psychiatry and Psychology, Department of Psychiatry, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, VIC, Australia.
Kylie M
KM
Gray
2 Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
Kristi-Ann
KA
Villagonzalo
1 IMPACT Strategic Research Centre (Barwon Health), Deakin University, Geelong, VIC, Australia.|2 Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
Seetal
S
Dodd
5 Biostatistics Unit, Faculty of Health, Deakin University, Burwood, VIC, Australia.
Mohammadreza
M
Mohebbi
1 IMPACT Strategic Research Centre (Barwon Health), Deakin University, Geelong, VIC, Australia.
Tanya
T
Vick
4 Centre for Developmental Psychiatry and Psychology, Department of Psychiatry, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, VIC, Australia.
Bruce J
BJ
Tonge
1 IMPACT Strategic Research Centre (Barwon Health), Deakin University, Geelong, VIC, Australia.|2 Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.|3 The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.|6 Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.
Michael
M
Berk
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D001321:Autistic Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017211:Treatment Failure
D016166:Free Radical Scavengers; D000111:Acetylcysteine
Autism; acetyl cysteine; clinical trial; spectrum