Antioxidant Supplement May Ease Autism Symptoms

Megan Brooks

June 01, 2012

June 1, 2012 — N-acetylcysteine (NAC), a specific antioxidant supplement, may be effective in easing irritability and repetitive behaviors in children with autism, a small pilot study suggests.

"There are at least 2 potential mechanism of action for NAC in autism," lead investigator Antonio Hardan, MD, from Stanford University School of Medicine, in Palo Alto, California, and director of the Autism and Developmental Disabilities Clinic at Packard Children's Hospital at Stanford, told Medscape Medical News.

Dr. Antonio Hardan

"The first one is related to the modulation of the glutamatergic system, which is known to be altered in autism. The other mechanism is due to NAC antioxidant effect. This role is supported by the evidence of abnormalities in the antioxidant defense system in autism," he added.

The study is published in the June 1 issue of Biological Psychiatry.

NAC Before Antipsychotics?

The 12-week, double-blind, randomized, placebo-controlled study involved 33 children (31 male, aged 3 to 12 years) with an autistic disorder and Clinical Global Impressions-Severity (CGI-S) score of 4 or greater.

NAC treatment consisted of 900 mg of NAC daily for 4 weeks, followed by 900 mg twice daily for 4 weeks, followed by 900 mg 3 times daily for 4 weeks. The NAC used in the study was a pharmaceutical-grade preparation donated by the neutraceutical manufacturer BioAdvantex Pharma.

Follow-up data were available on 14 children in the NAC arm and on 15 children in the placebo arm. Compared with placebo, NAC treatment was associated with a significant decrease in irritability scores (from 13.1 to 7.2) on the Aberrant Behavior Check List (ABC) irritability subscale (P < .001). Improvement was observed in week 4 and continued through weeks 8 and 12, the authors say.

The change is not as large as that seen in children taking antipsychotics, they say, "but this is still a potentially valuable tool to have before jumping on these big guns," Dr. Hardan commented in a prepared statement.

With oral NAC treatment, there was also a trend toward significant improvement of stereotypic/repetitive behaviors on the ABC (P < .096) and significant improvement on the Repetitive Behavior Scale-Revised (RBS-R) sterotypies subscale (P = .014).

Well Tolerated

NAC treatment did not significantly influence Social Responsiveness Scale (SRS) total raw scores (P = .141), but there were significant improvements in SRS social cognition (P = .037) and SRS autism mannerisms (P = .045) subscales.

"However, the improvements in SRS social cognition appear to be due to greater baseline impairment in the NAC group followed by regression to the mean rather than a true treatment effect," the authors write.

Consistent with previous studies, oral NAC was well tolerated with "minimal adverse effects," they note. The exception was 1 patient in the NAC group who experienced worsening of baseline agitation and irritability that required early termination, which was followed by symptom resolution. This patient had the same behavioral worsening 6 weeks after being terminated from the study. A medical evaluation revealed severe constipation.

Gastrointestinal side effects were the most commonly reported side effects. The mild side effect profile with NAC seen in this study and others is "important," the researchers note, because currently approved agents have a propensity to cause serious side effects (weight gain, metabolic abnormalities, and tardive dyskinesia), "which have limited their use considerably."

Potential for Other Neuropsychiatric Disorders

Dr. Hardan and colleagues say their findings "add to a growing list of studies reporting benefits from NAC in various neuropsychiatric disorders," including trichotillomania, schizophrenia, obsessive-compulsive disorder, and depression.

As previously reported by Medscape Medical News, Dr. Dean and her colleagues found that adjunctive NAC may be particularly helpful in treating the depressive phase of bipolar disorder. In an open-label study, they found that patients who had been diagnosed with bipolar disorder and who were given 2000 mg of NAC in addition to their usual treatment showed significantly lower symptom severity scores and increased functioning and quality-of-life scores.

Dr. Hardan said his team has submitted a grant to complete a multicenter trial to examine the effectiveness of NAC in the treatment of autism. The study will include more than 100 children with autism who are between the ages of 3 and 12 years.

"We would like also to examine its effect on irritability but also on restricted repetitive behaviors, since our preliminary studies have suggested potential effect in this domain," said Dr. Hardan.

Commenting on the study, Olivia Dean, PhD, from the Mental Health Research Institute and Deakin University School of Medicine in Victoria, Australia, who was not involved in the research, called it "innovative and important."

The study was supported by a grant from the Escher Family Fund at the Silicon Valley Community Foundation. Dr. Hardan has received research support from Bristol-Myers Squibb Company and Forest Pharmaceuticals. Stanford University is filing a patent for the use of NAC in autism, and one of the study authors has a financial stake in a company that makes and sells the NAC used in the trial. Dr. Dean has disclosed no relevant financial relationships.

Biol Psychiatry. 2012;71:956-961. Full article

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