Antioxidant Improves Behavior in Autism

Antioxidant could treat behavior problems in children with autism
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Behavior problems in children with autism are a frequent occurrence, and they can have a significant negative impact on a child's ability to adjust and function well at home, school, and in other social settings. Although treatment with drugs is one way to manage behavior problems in autism, another may be a common antioxidant.

Irritability is common in children with autism

The antioxidant is N-acetylcysteine (NAC), which is used both as a prescription drug and as a dietary supplement. In the former category, the Food and Drug Administration (FDA) approved NAC as a treatment of acetaminophen overdose. Clinical studies have shown that NAC can treat other toxic conditions as well, including drug-induced liver toxicity and toxicity from chemotherapy and radiation therapy.

The potential benefits of NAC in children and adolescents with autism was the focus of a recent study led by researchers at Stanford University and the Cleveland Clinic. The children were randomly assigned to take either a placebo or NAC daily for 12 weeks. Four evaluations were conducted throughout the study.

At the end of the study, the investigators found that irritability was significantly reduced in children who had taken NAC. The supplement also was well tolerated and associated with few side effects.

Why does NAC work in autism?
NAC is the precursor (substance that is present before or leads to another) to glutathione, a potent antioxidant, produced by the body, that helps control other antioxidants and is a key player in the antioxidant defense system. NAC helps restore and maintain levels of glutathione and thus protect brain cells, and it may also reduce the excitability of the glutamate system. Glutamate is a neurotransmitter in the brain that has a role in learning and memory.

NAC was chosen as a potential treatment for irritability and its related symptoms because of two ideas about autism: that it may be caused by an imbalance between antioxidants and oxidants, and that the glutamate system may not function properly in people with autism.

According to lead author Dr. Antonio Hardan, "Data from this preliminary trial suggest that NAC has the potential to be helpful in targeting irritability in children with autism." The study did not determine how NAC worked to improve irritability nor if NAC could be helpful in improving other symptoms of autism.

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Other treatments for behavior problems in autism
In 2006, the Food and Drug Administration approved the antipsychotic drug risperidone (Risperdal(R)) for the treatment of irritability associated with autistic disorder, including temper tantrums, rapidly changing moods, and self-injury. That was the first time the FDA had approved any medication for treatment of children and adolescents with autism.

Risperidone is associated with significant side effects, however. Approximately two-thirds of patients experience drowsiness, while about half have an increase in appetite and more than 20% experience insomnia, increase in salivation, fatigue, upper respiratory illness, tension, and anxiety. Less common side effects include abdominal pain, vomiting, indigestion, and giddiness.

Subsequently, the antipsychotic drug aripiprazole (Abilify) was approved for the same use, and a number of studies have been published on the use of this drug in young people with autism. In a new report from Texas A&M University, investigators presented the results of two 8-week, double-blind, placebo-controlled studies of aripiprazole on the quality of life in the treatment of irritability associated with autism.

A total of 316 children and adolescents (age 6-17 years) participated in the studies. Overall, participants who took aripiprazole scored significantly better on emotional functioning, social functioning, and cognitive functioning than did individuals who took placebo.

Side effects associated with aripiprazole include headache, weight gain, increase in appetite, nervousness, drowsiness, dizziness, heartburn, constipation, diarrhea, and pain in the arms, legs, or joints.

NAC for irritability in autism?
This new pilot study was a first step in discovering whether NAC will be added someday to the treatment arsenal for autism. More studies of this antioxidant are needed to determine its impact on behavior problems in autism spectrum disorder.

Sources:
Hardan AY et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biological Psychiatry 2012 Jun 1; 71(11)
Varni JW et al. Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials. Clinical Therapeutics 2012 Apr; 34(4): 980-92

Image: Morguefile

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