Nikoo 2015.

Study characteristics
Methods	Parallel trial of N‐acetylcysteine versus placebo
Participants	Inclusion criteria: children aged 4‐12 years of age meet the diagnostic criteria for autism according to the DSM‐4‐TR score > 6 in the DSM‐4 criteria baseline ABC‐I subscale score of ≥ 12 Exclusion criteria: history of psychotropic drug treatment within 6 weeks of enrolment tardive dyskinesia known adverse reaction to N‐acetylcysteine or risperidone taking concomitant medications with glutamatergic effects (e.g. dextromethorphan, D‐cycloserine, amantadine, memantine, lamotrigine, riluzole) other DSM‐IX axis I or II disorders any significant active medical problem severe intellectual disability that interfered with diagnosis of autism participation in any psychosocial intervention or concomitant drug during course of trial Location/setting: Tehran, Iran Sample size: 20 in N‐acetylcysteine + risperidone, 20 placebo + risperidone (40 in total) Number of withdrawals/dropouts: no reported dropouts after first post‐baseline measurements Gender: 33 male, 7 female Mean age: 7.5 years (N‐acetylcysteine), 7.6 years (placebo) IQ: not reported Baseline ABC‐I or other BoC: ABC‐I NAC 21.2, placebo 19.7 Concomitant medications: concomitant drug during course of trial not allowed History of previous medications: details not provided
Interventions	Intervention (N‐acetylcysteine) for 10 weeks: administered at 200 mg 3 times/day for children weighing < 20 kg. For children weighing ≥ 20 kg, N‐acetylcysteine was given at 300 mg 3 times/day. Risperidone was also started at 0.5 mg and titrated weekly by 0.5 mg to a maximum of 1.0 mg/day for children weighing < 20 kg. For children weighing ≥ 20 kg, risperidone was given at the same starting dose and titration rate, but to a maximum of 2.0 mg/day. Comparator (placebo) for 10 weeks: equivalent placebo
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: baseline, week 5, week 10
Notes	Study start date: November 2011 Study end date: November 2013 Source of funding: "this study was supported by a grant from Tehran University of Medical Sciences to Shahin Akhondzadeh, PhD, (grant no. 15155)." Conflicts of interest: none disclosed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random allocation of the patients into 2 groups in a 1:1 ratio with the help of computer‐generated codes
Allocation concealment (selection bias)	Low risk	Quote: "the assignments were kept in consecutively numbered, confidential, and sealed envelopes until the statistical analysis step"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided except double‐blinding used
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "during the study, separate persons held the responsibility of randomisation and rating of the patients. Resultant data were also entered in a database by a person not involved in other parts of the study"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Appears to have been no LTFU
Selective reporting (reporting bias)	Low risk	The trial was registered on http://irct.ir/trial/879 and all outcomes reported in the protocol were reported.
Other bias	High risk	The contact author is also on the ethics committee at the university funding the study. The contact author is a peer‐reviewer for one of the journals in which some of their studies are published.