Rezaei 2010.

Study characteristics
Methods	Parallel trial of topiramate + risperidone versus placebo + risperidone
Participants	Inclusion criteria: children 3‐12 years of age a score of ≥ 6 on DSM‐4‐TR criteria for diagnosis of autism an ABC‐C Irritability subscale score of ≥ 12 at screening and baseline Exclusion criteria: concomitant schizophrenia, psychotic disorders and epilepsy history of drug or alcohol abuse history of tardive dyskinesia any significant medical condition severe or profound intellectual disabilities in whom a definitive diagnosis of autism could not be made Location/setting: paediatric outpatient clinic in Iran Sample size: 40 (20 to each group) Number of withdrawals/dropouts: none reported Gender: 27 boys, 13 girls Mean age: topiramate + risperidone: 8.17 years; placebo + risperidone: 7.85 years IQ: not reported Baseline ABC‐I or other BoC: topiramate + risperidone: 17.25; placebo + risperidone: 16.80 Concomitant medications: not reported History of previous medications: not reported
Interventions	Topiramate + risperidone for 8 weeks: maximum topiramate dose of 100 mg/day for children < 30 kg or 3‐6 years of age. Maximum of 200 mg/day for children 7‐12 years or ≥ 30 kg. Maximum risperidone dose of 2 mg/day for children 10‐40 kg or 3 mg/day for children > 40 kg Risperidone + placebo for 8 weeks: maximum risperidone of 2 mg/day for children 10‐40 kg or 3 mg/day for children > 40 kg
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessment: AEs recorded at weeks 1, 2, 4, 6 and 8
Notes	Study start date: April 2008 Study end date: January 2010 Source of funding: grant from Tehran University of Medical Sciences to Prof Shahin Akhondzadeh (Grant No: 6550) Conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised to receive topiramate or placebo in a 1:1 ratio using a computer‐generated code.
Allocation concealment (selection bias)	Low risk	The assignments were kept in sealed, opaque envelopes until data analysis.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "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	Quote: "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	High risk	Quote: "Patients will be randomly allocated to topiramate + risperidone (Group A) or placebo + risperidone (Group B) for a 10‐week, double‐blind, placebo‐controlled study" only 8‐weeks of the trial was reported in the paper LTFU: none reported
Selective reporting (reporting bias)	High risk	The ABC and the 5 subscales were the primary outcome measure and were reported, however it is unexplained why the Iranian clinical trials website and the paper are different in terms of length of study. "Timepoint weeks 2‐4‐6‐8‐10 after beginning of trial".
Other bias	High risk	The Iranian clinical trial website says that timepoints are weeks 2‐4‐6‐8‐10 after beginning of trial, however, week 10 is not recorded in the paper and neither is a 2‐week follow‐up period. "Patients will be randomly allocated to topiramate + risperidone (Group A) or placebo + risperidone (Group B) for a 10‐week, double‐blind, placebo‐controlled study. The contact author is also on the ethics committee at the university funding the study and is a peer‐reviewer for one of the journals in which some of their studies are published.