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N-acetylcysteine calms irritability in autism

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A pilot trial of N-acetylcysteine (NAC) in children with autistic disorder has demonstrated reduced irritability with minimal adverse effects. Can NAC improve other symptoms as well?

A pilot trial of N-acetylcysteine (NAC) in children with autistic disorder has demonstrated markedly reduced irritability with minimal adverse effects.

In the 12-week double-blind, placebo-controlled study, researchers at Stanford University and the Cleveland Clinic randomized 31 boys and 2 girls aged 3 to 10 years with autistic disorder to receive oral NAC or placebo. The 14 children on NAC took 900 mg a day for 4 weeks, then 900 mg twice a day for 4 weeks, and finally 900 mg 3 times a day for 4 weeks. Irritability was measured using the irritability subscale of the Aberrant Behavior Checklist (ABC).

N-acetylcysteine significantly reduced irritability on the ABC subscale compared with placebo. Irritability can show up as aggression, tantrums, self-injury, and anger. The study found lesser improvement in other autism symptoms, notably repetitive and stereotyped behaviors, but the significance of the findings is unclear.

The children in the trial tolerated NAC well overall; the most common adverse effects included nausea, vomiting, and diarrhea. Tolerability is important, researchers note, because medications currently approved by the US Food and Drug Administration (FDA) to treat irritability can cause serious adverse effects including weight gain, metabolic abnormalities, and tardive dyskinesia.  
The investigators speculate that NAC, a glutamatergic modulator and antioxidant, may counteract glutamate system dysfunction and oxidant-antioxidant imbalance, which are thought to underlie some forms of autism. By raising the level of a protective antioxidant metabolite, NAC may prevent damage to brain cells. It may also decrease the excitability of the glutamate system by stimulating inhibitory receptors.

NAC is approved by the FDA to treat acetaminophen overdose by reducing liver damage related to depleted cysteine levels and impaired glutamate transmission.

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