A randomized controlled pilot trial of oral N-acetylcysteine in children with autism
- PMID:22342106
- PMCID: PMC4914359
- DOI: 10.1016/j.biopsych.2012.01.014
A randomized controlled pilot trial of oral N-acetylcysteine in children with autism
Abstract
Background: An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant, in the treatment of behavioral disturbance in children with autism.
Methods: This was a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist [ABC] irritability subscale) and safety measures were performed at baseline and 4, 8, and 12 weeks. Secondary measures included the ABC stereotypy subscale, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale.
Results: Thirty-three subjects (31 male subjects, 2 female subjects; aged 3.2-10.7 years) were randomized in the study. Follow-up data was available on 14 subjects in the NAC group and 15 in the placebo group. Oral NAC was well tolerated with limited side effects. Compared with placebo, NAC resulted in significant improvements on ABC irritability subscale (F = 6.80; p < .001; d = .96).
Conclusions: Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted.
Trial registration: ClinicalTrials.govNCT00627705.
Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Figures
Comment in
- Translating the Rosetta Stone of N-acetylcysteine.Dean OM, Bush AI, Berk M.Dean OM, et al.Biol Psychiatry. 2012 Jun 1;71(11):935-6. doi: 10.1016/j.biopsych.2012.04.001.Biol Psychiatry. 2012.PMID:22579303No abstract available.
Similar articles
- N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety.Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, Akhondzadeh S.Nikoo M, et al.Clin Neuropharmacol. 2015 Jan-Feb;38(1):11-7. doi: 10.1097/WNF.0000000000000063.Clin Neuropharmacol. 2015.PMID:25580916Clinical Trial.
- A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder.Wink LK, Adams R, Wang Z, Klaunig JE, Plawecki MH, Posey DJ, McDougle CJ, Erickson CA.Wink LK, et al.Mol Autism. 2016 Apr 21;7:26. doi: 10.1186/s13229-016-0088-6. eCollection 2016.Mol Autism. 2016.PMID:27103982Free PMC article.Clinical Trial.
- A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders.Ghanizadeh A, Moghimi-Sarani E.Ghanizadeh A, et al.BMC Psychiatry. 2013 Jul 25;13:196. doi: 10.1186/1471-244X-13-196.BMC Psychiatry. 2013.PMID:23886027Free PMC article.Clinical Trial.
- Aripiprazole for autism spectrum disorders (ASD).Ching H, Pringsheim T.Ching H, et al.Cochrane Database Syst Rev. 2012 May 16;(5):CD009043. doi: 10.1002/14651858.CD009043.pub2.Cochrane Database Syst Rev. 2012.Update in:Cochrane Database Syst Rev. 2016 Jun 26;(6):CD009043. doi: 10.1002/14651858.CD009043.pub3.PMID:22592735Updated.Review.
- Placebo-controlled augmentation trials of the antioxidant NAC in schizophrenia: A review.Chen AT, Chibnall JT, Nasrallah HA.Chen AT, et al.Ann Clin Psychiatry. 2016 Aug;28(3):190-6.Ann Clin Psychiatry. 2016.PMID:27490835Review.
Cited by
- Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines.Rose S, Wynne R, Frye RE, Melnyk S, James SJ.Rose S, et al.J Toxicol. 2015;2015:573701. doi: 10.1155/2015/573701. Epub 2015 Jan 21.J Toxicol. 2015.PMID:25688267Free PMC article.
- Improving Antioxidant Capacity in Children With Autism: A Randomized, Double-Blind Controlled Study With Cysteine-Rich Whey Protein.Castejon AM, Spaw JA, Rozenfeld I, Sheinberg N, Kabot S, Shaw A, Hardigan P, Faillace R, Packer EE.Castejon AM, et al.Front Psychiatry. 2021 Sep 30;12:669089. doi: 10.3389/fpsyt.2021.669089. eCollection 2021.Front Psychiatry. 2021.PMID:34658941Free PMC article.
- Deletion ofFmr1 results in sex-specific changes in behavior.Nolan SO, Reynolds CD, Smith GD, Holley AJ, Escobar B, Chandler MA, Volquardsen M, Jefferson T, Pandian A, Smith T, Huebschman J, Lugo JN.Nolan SO, et al.Brain Behav. 2017 Aug 25;7(10):e00800. doi: 10.1002/brb3.800. eCollection 2017 Oct.Brain Behav. 2017.PMID:29075560Free PMC article.
- The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation.Jurnak F.Jurnak F.Nutr Metab Insights. 2016 Jun 14;8(Suppl 1):57-77. doi: 10.4137/NMI.S29531. eCollection 2015.Nutr Metab Insights. 2016.PMID:27330305Free PMC article.
- Treatment of Autism Spectrum Disorder in Children and Adolescents.DeFilippis M, Wagner KD.DeFilippis M, et al.Psychopharmacol Bull. 2016 Aug 15;46(2):18-41.Psychopharmacol Bull. 2016.PMID:27738378Free PMC article.
References
- Belmonte MK, Cook EH, Jr, Anderson GM, Rubenstein JL, Greenough WT, Beckel-Mitchener A, et al. Autism as a disorder of neural information processing: directions for research and targets for therapy. Mol Psychiatry. 2004;9:646–663. - PubMed
- Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J Toxicol Environ Health B Crit Rev. 2006;9:485–499. - PubMed
- Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 2001;57:1618–1628. - PubMed
Publication types
MeSH terms
Substances
Associated data
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources