DeVane 2019.

Study characteristics
Methods	10‐week trial of aripiprazole versus risperidone
Participants	Inclusion criteria: aged 6‐17 years weighing at least 15 kg meet DSM‐4 criteria for ASD ABC‐Irritability subscale score of > 18 at baseline mental age of at least 18 months medication‐free or adequate washout period (2‐4 weeks prior) of psychotropic medications Exclusion criteria: psychiatric disorder that is being treated with psychotropic drugs prior diagnosis or evidence of other disorders that may interfere with assessment (e.g Fragile X, fetal alcohol syndrome) prior use of aripiprazole or risperidone for > 2 weeks seizure during the last 6 months medical condition that may place the participant at increased risk of significant AEs dependent on other substances excluding nicotine or caffeine positive urine pregnancy test at baseline. Location/setting: 3 academic medical centres and a single private paediatric practice in the USA Mean age: range 6‐15.1 years in aripiprazole group; 6.3‐17.5 years in risperidone group IQ: details not provided Gender: 19% and 23% of aripiprazole and risperidone groups were female. Current or previous medications: aripiprazole, 4/31 had previously taken the study drug (but not within the last 3 years), risperidone, 1/31 had previously taken the study drug (but not within the last 3 years). Baseline ABC‐Irritability scores: > 18 at baseline Sample size: 61 (31 aripiprazole; 30 risperidone) Number analysed: aripiprazole 31, risperidone 30 Reason for dropouts: aripiprazole, 4 discontinued all due to AEs, risperidone, 6 discontinued (3 due to missed visits, 2 AEs, and 1 withdrew on physician's advice) Timing of outcome assessments: "safety, physical, and psychological assessment were recorded at clinic visits that took place weekly or every 2 weeks".
Interventions	Intervention (risperidone): "children weighing 20‐45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day" Comparator (aripiprazole): starting dosage of 2.0 mg/day. "The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter to a maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks".
Outcomes	Primary outcomes: ABC‐Irritability (Aman 1985); AEs Secondary outcomes: tolerability
Notes	Study start date: September 2011 Study end date: June 2015 Funding: "The study was funded by Grant No. R01HD62550 from the National Institute of Child Health and Human Development, National Institutes of Health". Conflicts of interest: "The authors have declared no conflicts of interest for this article". Trial registry: NCT01333072
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details given on how random sequence was generated
Allocation concealment (selection bias)	Unclear risk	No details given on allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All research personnel blinded except for RA who prepared meds and study pharmacist who checked meds
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Physicians (who conducted physical neurological evaluation) and caregiver (who completed questionnaires) were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were accounted for and included in the analysis.
Selective reporting (reporting bias)	High risk	Protocol available at ClinicalTrials.gov Identifier: NCT01333072 Primary outcome was "Changes in the Irritability Subscale of the Larger ABC (Abberent Behavior Checklist) That Occur From Baseline to 10 Weeks" but they've tested for P values at each week as there was no statistically significant difference at 10 weeks. This is reported misleadingly in the abstract Quote: "Improvement was greatest in the risperidone group at every assessment period"
Other bias	Low risk	None identified