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N-Acetylcysteine as an Adjunctive Therapy to Risperidone for Treatment of Irritability in Autism

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety

Nikoo, Mohammadali MD; Radnia, Hanieh MD; Farokhnia, Mehdi MD; Mohammadi, Mohammad-Reza MD; Akhondzadeh, Shahin PhD

doi: 10.1097/WNF.0000000000000063
Original Articles

Objectives According to the proposed interference of N-acetylcysteine (NAC) with pathophysiologic processes of autistic disorders (ADs), we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized, double-blind, clinical trial.

Methods The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale score. The participants were randomized into 2 groups. One group received risperidone plus NAC, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in other subscales were considered as secondary outcome measures.

Results Forty patients completed the 10-week trial. Baseline characteristics including age, sex and body weight, as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups. Repeated-measures analysis showed significant effect for time × treatment interaction in irritability (P = 0.01) and hyperactivity/noncompliance (P = 0.02) subscales. By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores.

Conclusions N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes.

Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Address correspondence and reprint requests to Shahin Akhondzadeh, PhD, Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, S Kargar St, Tehran 13337, Iran; E-mail:

Conflicts of interest and source of funding: This study was supported by a grant from Tehran University of Medical Sciences to Shahin Akhondzadeh, PhD, (grant no. 15155). For the remaining authors, none were declared. The funding organization had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript and the decision to submit the paper for publication.

The first 2 authors contributed equally to this work.

Clinical Trial registry name and registration number: Iranian registry of clinical trials, IRCT201110281556N29

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