Ghaleiha 2013a.

Study characteristics
Methods	Parallel trial of memantine versus placebo
Participants	Inclusion criteria: children aged 4‐12 years meet the DSM‐4‐TR criteria for diagnosis of autism ABC‐C I subscale score of ≥ 12 at screening at baseline Exclusion criteria: concomitant schizophrenia or psychotic disorders severe intellectual disabilities active clinical seizures history of drug or alcohol abuse or tardive dyskinesia any antipsychotic drug treatments in the previous 6 months previously used memantine any significant active medical problem Location/setting: speciality clinic for autism in the children’s outpatient clinic, Iran Sample size: 40 (20 memantine/risperidone; 20 placebo/risperidone) Number of withdrawals/ dropouts: none reported Gender: memantine 11 boys, 9 girls; placebo 12 boys, 8 girls Mean age: memantine 7.42 years; placebo 7.97 years IQ: not reported Baseline ABC‐I or other BoC: ABC‐I memantine 18.25, placebo 17.65 Concurrent medications: 0% (participants had to be drug‐treatment‐free in 6 months prior to trial) History of previous medications: not reported
Interventions	Intervention (memantine + risperidone) for 10 weeks: participants started on 5 mg (tablets) once daily, which was titrated up or down in 5 mg increments each week up to a maximum of 15 mg/day for children 10‐40 kg and 20 mg/day for children > 40 kg. Risperidone was titrated up to 2 mg/day (starting at 0.5 mg with dose increases of 0.5 mg increments weekly for the first 3 weeks) for children weighing 10‐40 kg, titrated up to 3 mg/day for children > 40 kg Comparator (placebo + risperidone) for 10 weeks: placebo was identical to memantine in appearance, shape, size, colour and taste. Risperidone was titrated up to 2 mg/day (starting at 0.5 mg with dose increases of 0.5 mg increments weekly for the first 3 weeks) for children weighing 10‐40 kg, titrated up to 3 mg/day for children > 40 kg
Outcomes	Primary outcomes: irritability, measured using the ABC‐Irritability subscale (Aman 1985); AEs Secondary outcomes: none reported Timing of outcome assessments: ABC‐I was rated at baseline, weeks 2, 4, 6, 8 and 10; AEs were recorded every 2 weeks
Notes	Study start date: January 2009 Study end date: January 2011 Source of funding: Tehran University of Medical Sciences Conflicts of interest: none declared Trial registry ‐ IRCT1138901151556N10
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomised to receive memantine or placebo in a 1:1 ratio using a computer‐generated code"
Allocation concealment (selection bias)	Unclear risk	Quote: "the assignments were kept in sealed, opaque envelopes until data analysis." But it is not clear how they were allocated.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Throughout the study the person who administered the medications, the rater and the patients were blind to assignments.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Throughout the study, the person who administered the medications, the rater and the patients were blind to assignments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There appeared to be no LTFU
Selective reporting (reporting bias)	Low risk	All data appear to have been 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.