Article

A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
Biological psychiatry (Impact Factor: 9.47). 02/2012; 71(11):956-61. DOI: 10.1016/j.biopsych.2012.01.014
Source: PubMed

ABSTRACT An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant, in the treatment of behavioral disturbance in children with autism.
This was a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist [ABC] irritability subscale) and safety measures were performed at baseline and 4, 8, and 12 weeks. Secondary measures included the ABC stereotypy subscale, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale.
Thirty-three subjects (31 male subjects, 2 female subjects; aged 3.2-10.7 years) were randomized in the study. Follow-up data was available on 14 subjects in the NAC group and 15 in the placebo group. Oral NAC was well tolerated with limited side effects. Compared with placebo, NAC resulted in significant improvements on ABC irritability subscale (F = 6.80; p < .001; d = .96).
Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted.

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    • "Alternative shuttling of electrons to cytochrome c bypassing complex I/III seems to have a role for neuroprotection through enhancing the production of ATP and lowering the production of ROS (Wen et al., 2011; Rojas et al., 2011; Ghanizadeh et al., 2013). A potential therapeutic effect of N-Acetyl cysteine has been reported in clinical trials involving children with autism (Ghanizadeh and Derakhshan, 2012; Hardan et al., 2012). Mitochondrial-targeted molecules and nutrients, such as coenzyme Q(10), acetyl-l-carnitine, ␣-lipoic acid, ␣-tocopherol and ascorbic acid, that support mitochondrial functions and reduce OS have been long investigated for treatment of Down syndrome (reviewed in Pagano and Castello, 2012; Lott et al., 2011). "
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    • "Importantly, NAC was well tolerated, as has been the case in children with autism (Hardan et al. 2012), in adolescents with cannabis dependence (Gray et al. 2012), in adults with trichotillomania (Grant et al. 2009), and when used adjunctively with SSRIs, in adults with SSRI-resistant anxiety disorders (Lafleur et al. 2006). Additional, prospective trials are urgently needed to assess the potential role of glutamate modulators, such as NAC, in youth with anxiety disorders, including those who have had partial responses to ''first-line'' psychopharmacologic and psychotherapeutic interventions. "
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