A randomized controlled pilot trial of oral N-acetylcysteine in children with autism
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Additional improvements were seen in stereotypic behaviors with significance reached on the RBS-S Stereotypies subscale (p < 0.014) and the SRS Autism Mannerisms subscale (p < 0.045) for those treated with NAC vs placebo.
“Additional improvements were seen in stereotypic behaviors with significance reached on the RBS-S Stereotypies subscale (p < 0.014) and the SRS Autism Mannerisms subscale (p < 0.045) for those treated with NAC vs placebo [62].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [62]
NAC was well tolerated although an occasional patient did not like the taste or had minimal gastrointestinal side-effects.
“NAC was well tolerated although an occasional patient did not like the taste or had minimal gastrointestinal side-effects.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [62]
In a controlled trial of escalating doses of NAC vs placebo in 33 subjects with ASD ages 3.2 to 10.7 years, after 12 weeks there was significant improvement on the primary outcome measure, irritability subscale on the ABC (p < 0.001) for patients treated with NAC compared to placebo.
“They randomized 33 subjects with ASD ages 3.2 to 10.7 years and after 12 weeks of treatment they found significant improvement on their primary outcome measure, irritability subscale on the ABC (p < 0.001) for patients treated with NAC compared to placebo.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [62]
NAC works by two mechanisms to lower the E:I imbalance; it lowers glutamatergic neurotransmission, and the cysteine leads to an increase in glutathione synthesis which is an important antioxidant.
“NAC works by two mechanisms to lower the E:I imbalance; it lowers glutamatergic neurotransmission, and the cysteine leads to an increase in glutathione synthesis which is an important antioxidant.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 44 · Cited by 293
- Authors
- Hardan, A. Y., Fung, L. K., Libove, R. A., Obukhanych, T. V., Nair, S., Herzenberg, L. A., Frazier, T. W., & Tirouvanziam, R.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Cleveland Clinic (US)
- Corresponding author
- Hardan, Antonio Y.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 71
- Issue
- 11
- Pages
- 956-961
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4914359
- OpenAlex
- W2147802796
- Cited by
- 293
- References
- 44
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 16 · 2023: 17 · 2022: 17 · 2021: 22 · 2020: 22 · 2019: 17 · 2018: 23 · 2017: 18 · 2016: 27 · 2015: 28 · 2014: 24 · 2013: 22 · 2012: 10
- FWCI
- 13.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Silicon Valley Community Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- N-acetylcysteine, autism spectrum disorder, irritability, glutamatergic pathways, redox imbalance, antioxidant therapy, behavioral problems, children, treatment feasibility, adverse effects, social responsiveness
- MeSH terms
- Acetylcysteine, Autistic Disorder, Child, Child, Preschool, Double-Blind Method, Female, Humans, Irritable Mood, Male, Pilot Projects, Stereotyped Behavior, Free Radical Scavengers, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
