Mohammadi 2013.

Study characteristics
Methods	Parallel trial of amantadine + risperidone versus placebo + risperidone
Participants	Inclusion criteria: outpatients aged 4‐12 years diagnosis of autism based on DSM‐4, score of ≥ 12 ABC‐I subscale at screening/baseline, "presenting with chief complaint of severely disruptive symptoms related to autistic disorder so that risperidone was indicated as a medical intervention". Exclusion criteria: other diagnoses on Axis I or II except for intellectual disability, severe intellectual disability, which makes the diagnosis of autism inconclusive (based on clinical judgement of the child psychiatrist) any significant active medical problem including hepatic diseases as well as history of seizure and allergy to amantadine or risperidone received any psychotropic medication within 6 weeks before enrolment Location/setting: a psychiatric academic hospital affiliated with Tehran University of Medical Sciences, Iran Sample size: 40 (20 in each group) Number of withdrawals/dropouts: 1 participant in the risperidone plus placebo group discontinued after week 5. Gender: amantadine 16/20 boys; placebo 17/20 boys Mean age: amantadine 6.4 years; placebo 7.1 years IQ: not reported Baseline ABC‐I or other BoC: ABC‐I amantadine group 20; ABC‐I placebo 20.9 Concomitant medications: not reported History of previous medications: not reported
Interventions	Amantadine + risperidone for 10 weeks: amantadine was given twice a day at 100 mg/d for children < 30 kg, and 150 mg/d for those ≥ 30 kg. Risperidone was started at 0.5 mg/day, and titrated up to 2.0 mg/day in a 0.5 mg/week rate if there were no complications. Placebo + risperidone for 10 weeks: risperidone was started at 0.5 mg/day, and titrated up to 2.0 mg/day in a 0.5 mg/week rate if there were no complications. Placebo was identical in appearance (shape, size, colour, and taste) and dispensed by investigational drug pharmacist, alongside risperidone, which started at 0.5 mg/day, and was titrated up to 2.0 mg/day in a 0.5 mg/week rate if there were no complications.
Outcomes	Primary outcomes: irritability, measured using the ABC‐Irritability subscale (Aman 1985) AEs Secondary outcomes: not reported Timing of outcome assessments: baseline, 5 weeks, 10 weeks (endpoint)
Notes	Study start date: June 2011 Study end date: May 2012 Source of funding: supported by a grant from Tehran University of Medical Sciences (grant 10797) Conflicts of interest: "no conflict of interest exists for any of the authors associated with the manuscript and there was no source of extra‐institutional commercial funding".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was accomplished using a computerised random number generator in a 1:1 ratio and blocks of 4
Allocation concealment (selection bias)	Low risk	Quote: "treatment allocation was concealed from the patients and the rating psychiatrists using sequentially numbered, opaque, sealed, and stapled envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Separate persons were responsible for random allocation and rating of the patients. The patients, the psychiatrists who referred them, the clinician who assessed the patients and prescribed the drugs, and the statistician were blind to the allocations."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The patients, the psychiatrists who referred them, the clinician who assessed the patients and prescribed the drugs, and the statistician were blind to the allocations."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All analyses were based on the ITT sample and were performed using LOCF procedure on participants with at least 1 post‐baseline visit.
Selective reporting (reporting bias)	Low risk	All outcomes reported in the trial protocol on the Iranian Registry of Clinical trials were reported in the paper.
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.