N-acetylcysteine Improved the Irritability Associated with Autism

November 1, 2011 · Posted in Potential Treatments 

autistic boyAt the 57th Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) in October 2010, Lawrence Fung of Stanford University reported that N-acetylcysteine (NAC), a compound sold over-the-counter in health food stores, improved irritability and other symptoms of autism in children aged 8 to 17. In this double-blind, randomized study of NAC compared with placebo, the children who received NAC were treated with 900mg once a day for four weeks, then 900mg BID (twice a day) for four weeks, and finally 900mg TID (three times a day) for the last four weeks of this three-month study. These doses significantly improved irritability and stereotypy (repetitive behaviors) compared with placebo. Side effects were minimal.

Editor’s note:  The potential for a safe compound such as N-acetylcysteine to show efficacy in autism is striking. Currently only risperidone and aripiprazole are FDA-approved for effectiveness treating irritability in autism.  There has also been a positive study of valproate compared with placebo in autism, although it is not FDA-approved for this purpose.

Most double-blind, placebo controlled clinical trials of NAC have been in adults, so this is the first report that suggests NAC can safely be used in children.

NAC’s ability to improve irritability in autism raises the possibility that this drug may be useful in the treatment of irritability and repetitive behaviors in bipolar disorder, particularly since N-acetylcysteine has also been reported to improve mood, especially depression, in adults with bipolar disorder in the studies of Mike Berk and colleagues published in Biological Psychiatry in 2008.

This study adds to the evidence that suggests N-acetylcysteine may reset the brain’s habit system in the ventral striatum (also called the nucleus accumbens), which is involved in the assessment of the reward value of a variety of substances of abuse and behaviors (as described in BNN Volume 14, Issue 1 from 2010).  NAC improves a number of habit-related syndromes including cocaine, heroin, and gambling addictions, trichotillomania (compulsive hair-pulling), and now the irritability and stereotypic behaviors of autism.

In light of NAC’s profile of efficacy and safety, systematic exploration of the drug in childhood-onset bipolar illness is indicated. We are aware of at least one group that is planning such a study.

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