The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine by Richard Eugene Frye & Michael Berk

Author:Richard Eugene Frye & Michael Berk
Language: eng
Format: epub
ISBN: 9789811053115
Publisher: Springer Singapore

12.3.3 Autism Spectrum Disorder (ASD)

ASD is a behaviorally defined disorders characterized by deficits in communication and socialization, along with the presence of restricted interests and/or repetitive behaviors (APA 2013). It is currently estimated to affect 1 in 65 children in the United States (CDC 2012). While the etiology of ASD is largely unknown, a growing body of evidence suggests that mitochondrial dysfunction (Rossignol and Frye 2012a, b, 2014; Rose et al. 2017), oxidative stress and abnormalities in redox regulation (Rossignol and Frye 2012b, 2014; Frye and James 2014), immune dysfunction and inflammation (Rossignol and Frye 2012b, 2014), environmental toxicants (Rossignol and Frye 2012b; Rossignol et al. 2014), and disruption in other metabolic processes (Frye and Rossignol 2016; Frye and Rossignol 2014) including folate (Frye et al. 2013b, 2016b, c) and cobalamin (Frye et al. 2013a) may be involved in the pathophysiology of ASD. Attention has focused on interventional strategies that can target these pathophysiological abnormalities, and some of the mechanisms of action of NAC involve the aforementioned pathways.

An overall GOR for NAC in ASD is B (Supplementary Table 12.3). This rating is based on five controlled trials with a total of 3.5 points leading to a 70% positive rating on controlled trials (Hardan et al. 2012; Ghanizadeh and Moghimi-Sarani 2013; Nikoo et al. 2015; Wink et al. 2016; Dean et al. 2017) and four positive uncontrolled trials (Ghanizadeh and Derakhshan 2012; Marler et al. 2014; Stutzman and Dopheide 2015; Celebi 2017) leading to a 100% positive rating on uncontrolled trials. This resulted in a recommendation of “mixed,” although the large number of positive trials suggests this is a promising treatment.

Although the most recent controlled trials failed to show improvements on clinical endpoints, the one that measured glutathione metabolism demonstrated NAC improvement in oxidative stress (Wink et al. 2016). While Hardan et al. (2012) found NAC to be safe and effective at addressing irritability in children with ASD, other researchers have looked at NAC to try and improve social abilities in children with ASD (Dean et al. 2017; Wink et al. 2016). Irritability and aggression appear to be symptoms that have repeatedly been shown to improve in many of the controlled (Ghanizadeh and Moghimi-Sarani 2013; Hardan et al. 2012; Nikoo et al. 2015) and open-labeled (Stutzman and Dopheide 2015; Ghanizadeh and Derakhshan 2012; Marler et al. 2014) trials, suggesting that these may be key symptoms to concentration on future high-quality clinical studies. Interestingly, Two controlled study specifically looked at the ability of NAC to complement risperidone, a medication primary used to treat irritability and aggression (Nikoo et al. 2015; Ghanizadeh and Moghimi-Sarani, 2013). One of the negative controlled trials used an unusually low dose of NAC, raising the question of a significant limitation of the study (Dean et al. 2017). Overall, NAC was very well tolerated in most of the studies. The exception is the one case report with mild abdominal pain (Ghanizadeh and Derakhshan 2012) andone controlled study with severe constipation (Hardan et al. 2012). Given that children with ASD commonly have gastrointestinal symptoms (Buie et al.

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