Autism is a developmental disorder that affects social and communication skills. Irritability is a symptom of autism that can complicate adjustment at home and other settings, and can manifest itself in aggression, tantrums, and self-injurious behavior. These disruptive behaviors are frequently observed in children with autism, which may considerably affect their ability to function at home or in school.
N-acetylcysteine (NAC) is approved by the US Food and Drug Administration for the treatment of acetaminophen (Tylenol) overdoses, but it may have other applications related to its effects in the brain. NAC helps maintain and restore glutathione, which play a key role in the antioxidant defense system. Additionally, cysteine as supplied by NAC treatment, stimulates a protein, the cystine-glutamate antiporter, resulting in the decrease of glutamatergic neurotransmission. NAC has two resulting effects: 1) it may protect brain cells by raising the level of a protective antioxidant metabolite called glutathione, and 2) it may reduce the excitability of the glutamate system by stimulating inhibitory receptors.
These drug actions are important because, although the causes of autism are unknown, it is clear that there are many influencing factors and scientists are pursuing multiple hypotheses. Two in particular relate to NAC: one theory is that autism may be caused by an imbalance between oxidants and antioxidants in the body; the other is that the glutamate system may be dysfunctional in individuals with autism.
These hypotheses led researchers at Stanford University and the Cleveland Clinic to conduct a pilot trial of NAC in children with autistic disorder. Children were randomized to receive either NAC or placebo daily for 12 weeks and their symptoms were evaluated four times during that period.
They found that irritability was significantly decreased in the children who received NAC. In addition, NAC was well-tolerated and caused minimal side effects.
Lead author Dr. Antonio Hardan commented, “Data from this preliminary trial suggest that NAC has the potential to be helpful in targeting irritability in children with autism. It is also unclear if NAC improves other symptom domains in autism.”
“At this point it is too early to tell how NAC reduced irritability in autism, but this finding will be an important addition to the field if it can be replicated,” said Dr. John Krystal, Editor of Biological Psychiatry, where the study is being published.
Dr. Hardan agreed, adding that “large randomized controlled trials are needed to attempt to replicate the findings from this pilot trial and to determine whether or not NAC is effective in targeting other symptoms observed in autism such as repetitive and restricted interests.” This small pilot study was the first step and so the next stages of work can now begin to determine whether NAC could potentially become an approved treatment for autism.
The article is “A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism” by Antonio Y. Hardan, Lawrence K. Fung, Robin A. Libove, Tetyana V. Obukhanych, Surekha Nair, Leonore A. Herzenberg, Thomas W. Frazier, and Rabindra Tirouvanziam (doi: 10.1016/j.biopsych.2012.01.014). The article appears in Biological Psychiatry, Volume 71, Issue 11 (June 1, 2012), published by Elsevier.
The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.