A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders

BMC Psychiatry, Jul 2013

Background This study examined the efficacy and safety of N-acetylcysteine (NAC) augmentation for treating irritability in children and adolescents with autism spectrum disorders (ASD). Method Forty children and adolescents met diagnostic criteria for ASD according to DSM-IV. They were randomly allocated into one of the two groups of NAC (1200 mg/day)+risperidone or placebo+risperidone. NAC and placebo were administered in the form of effervescent and in two divided doses for 8 weeks. Irritability subscale score of Aberrant Behavior Checklist (ABC) was considered as the main outcome measure. Adverse effects were also checked. Results The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. Repeated measures of ANOVA showed that there was a significant difference between the two groups after 8 weeks. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect. Conclusions Risperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with ASD. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well. Trial registration This trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6

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A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders

BMC Psychiatry A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders Ahmad Ghanizadeh 0 1 2 Ebrahim Moghimi-Sarani 0 2 0 Department of Psychiatry, Shiraz University of Medical Sciences, School of Medicine , Shiraz , Iran 1 Research Center for Psychiatry and Behavioral Sciences, Shiraz University of Medical Sciences, School of Medicine , Shiraz , Iran 2 Keyword: Autism, Clinical trial, Randomized, Therapy , N-acetylcysteine, Oxidative stress Background: This study examined the efficacy and safety of N-acetylcysteine (NAC) augmentation for treating irritability in children and adolescents with autism spectrum disorders (ASD). Method: Forty children and adolescents met diagnostic criteria for ASD according to DSM-IV. They were randomly allocated into one of the two groups of NAC (1200 mg/day)+risperidone or placebo+risperidone. NAC and placebo were administered in the form of effervescent and in two divided doses for 8 weeks. Irritability subscale score of Aberrant Behavior Checklist (ABC) was considered as the main outcome measure. Adverse effects were also checked. Results: The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. Repeated measures of ANOVA showed that there was a significant difference between the two groups after 8 weeks. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect. Conclusions: Risperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with ASD. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well. Trial registration: This trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6 - Background Autism spectrum disorders (ASD) are characterized by the three main symptoms of: a) significant impairments in social relationships, b) language and communication deficits, and c) restricted interests. Although, autistic disorders are not very common, their current rates are higher than that of the previously reported rates [1]. About 1.9% of school aged children obtain screening cutoff score for probable autistic disorder [2]. The rate for typical autism in five-year-old children is 6.26 per 10,000 [3]. In addition, the global prevalence of autism spectrum disorders is 62/10 000 [4]. The neurobiology and etiology of autism are not clearly known [5]. However, genetic [6], neurologic, metabolic, and immunologic factors are suggested to be involved. It is proposed that there is an imbalance of oxidative stress and anti-oxidative defenses in children with autism [7,8]. The deficit in antioxidant system is specific in autism [9] and it mediates the association of some behavioral symptoms and immunity function [10]. While plasma antioxidant capacity is decreased [11], the plasma oxidative stress indicators, such as nitric oxide (NO) and malondialdehyde (MDA), are increased [12]. In addition, lipid peroxidation is increased in autism [13]. Oxidative stress markers in urine may represent oxidative stress index in autistic patients and some of them are suggested as the biomarkers of autism [14]. The levels of superoxide dismutase (SOD) and glutathione peroxidase, as antioxidant enzymes, are lower in autism than that of the controls [15]. Oxidative stress negatively affects mitochondrion through respiratory chain [16]. Therefore, oxidative stress is suggested as a target for treating autism [7,17]. In addition, animal models of autism revealed that targeting oxidative markers was effective for treating autism [18]. Glutathione plays a significant role in defense against oxidative stress in autism [7,19]. The level of glutathione in the cerebellum and temporal cortex of patients with autism are markedly decreased (34.2% and 44.6%, respectively) [20]. The levels of both reduced glutathione and total glutathione are lowered in autistic patients than that of the controls [21]. Moreover, glutathione pathway gene variation increases the risk of autistic disorders [22]. Glutathione, which is the most important intracellular defense against oxidative stress, consists of glutamate, glycine, and cysteine [7]. The pathways of methionine cycle, transsulfuration pathway, and GSH-synthesis pathway produce glutathione [23]. The role of cysteine for the production of glutathione is very important because cysteine has a rate-limiting role [7]. Recently, an eight-week, open-label trial showed that glutathione supplementation increased the reduced-form of glutathione in plasma in children with autism spectrum disorders [24]. This supplementation also incre (...truncated)


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Ahmad Ghanizadeh, Ebrahim Moghimi-Sarani. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders, BMC Psychiatry, 2013, pp. 196, 13, DOI: 10.1186/1471-244X-13-196