Hendouei 2019.

Study characteristics
Methods	10‐week trial of resveratrol + risperidone versus placebo + risperidone
Participants	Inclusion criteria: DSM‐5 clinical diagnosis of ASD children between the ages of 3 and 12 years presence of behavioural problems such as aggression, overactivity or repetitive behaviours (indication of treatment with risperidone) Both "male and female outpatients referred to our clinic from different parts of Iran with probable autistic signs and symptoms". Exclusion criteria: presence of any active medical problem other psychiatric diagnosis except for mild to moderate intellectual disability receiving any antipsychotic medications during past month prior to the trial severe hepatic disease history of allergy to risperidone and intolerance of it history of seizure requiring change of antiepileptic dose during the last month seizure during the last 6 months Location/setting: autism clinic in children's outpatient clinic of Roozbeh Hospital (Tehran University of Medical Sciences, Tehran, Iran) Sample size: resveratrol (35); placebo (35) Number of withdrawals/dropouts: resveratrol (4, 2 ineligible to continue, 2 consent withdrawn); placebo (4, 4 consent withdrawn) Gender: 50 male, 12 female Mean age: resveratrol 7.8 (2.1); placebo: 8.1 (1.9) IQ: details not provided Baseline ABC‐I or other BoC: ABC‐I of > 22 at baseline across both groups Concomitant medications: apart from resveratrol and risperidone no other concomitant medications were allowed in either group. History of previous medications: antipsychotics could not be taken in month prior to the study and any anticonvulsant use could not have changed in month prior to study
Interventions	Intervention (resveratrol + risperidone): both groups were treated with risperidone twice daily, starting at a dose of 0.5 mg, with a dose increase of 0.5 mg per week (for the first 3 weeks). Resveratrol dosage was 250 mg twice per day from the beginning of the study. Comparator (placebo + risperidone): both groups were treated with risperidone twice daily, starting at a dose of 0.5 mg with a dose increase of 0.5 mg/week (for the first 3 weeks) plus placebo for 10 weeks.
Outcomes	Primary outcomes: irritability, measured using the ABC‐I (Aman 1985) AEs Secondary outcomes: tolerability Timing of outcome assessments: baseline, week 5 and week 10 (endpoint)
Notes	Study start date: January 2018 Study end date: April 2019 Funding: "This study was supported by a grant from Tehran University of Medical Sciences to Prof. Shahin Akhondzadeh (Grant No: 36420)" Conflicts of interest: "None of the authors in this study had conflict of interest of any kind with the parties that might be involved." Trial registry: IRCT20090117001556N104
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Using the Microsoft Office Excel software, each patient was assigned to a specific random code."
Allocation concealment (selection bias)	Low risk	The assignments were retained in confidential and sealed opaque envelops and were unveiled at the study endpoint for statistical analysis.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "all individuals involved in this study, such as patients and researchers, were blinded to the assignments."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Separate individuals were responsible for randomisations, drug administration, rating, data entry and statistical analysis. Furthermore, all individuals involved in this study, such as patients and researchers, were blinded to the assignments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition, and all participants were accounted for
Selective reporting (reporting bias)	High risk	Doesn't report CARS (primary outcome on trial reg) and measurement time points different to trial reg
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.