Hollander 2006b.

Study characteristics
Methods	Parallel trial of olanzapine versus placebo
Participants	Inclusion criteria: age 6‐17 years meet DSM‐5 and ADI‐R criteria with a rating of at least moderate (≥ 4) on the CGI Scale free of psychotropic medications for at least 4 weeks prior to starting the study drug except stable dose (at least 3 months) of anticonvulsants for seizures or clonidine or chloral hydrate given only at bedtime for sleep "children in an established programme for at least 3 months prior to starting the trial and kept constant throughout the medication trial could be included in the study". Exclusion criteria: responded well to prior pharmacological treatment psychotic disorders history of any clinically significant medical illness (with the exception of a stable seizure disorder) Location/setting: details not provided Sample size: 11 in total, 6 olanzapine group, 5 placebo Number of withdrawals/dropouts: "one child dropped out right after randomization due to parental disagreement regarding study participation. Two others dropped out during the study because their parents were noncompliant with their follow up appointments." Gender: all were male in the olanzapine group, placebo 3/5 were male Mean age: olanzapine 9.25 years, placebo 8.9 years IQ: 2 in olanzapine group had severe intellectual disability, 5 participants had mild intellectual disability (2 and 3 in placebo), 4 had normal cognitive function (2 in each group) Baseline ABC‐I or other BoC: not applicable Concomitant medications: 0% History of previous medications: not reported
Interventions	Intervention (olanzapine) for 8 weeks: "in children weighing less than 40kg, the dosage started with 2.5mg of olanzapine every other day; after 3 days, the dose increased to 2.5mg every day. In children weighing more than 40kg, the dose started at 2.5mg every day and was increased to 5mg/day after 3 days/ Thereafter, the dosage for both weight groups was increased in 5‐mg increments weekly to a maximum of 20mgday" Comparator (placebo) for 8 weeks: equivalent placebo
Outcomes	Primary outcomes: AEs Secondary outcomes: none reported Timing of outcome assessments: baseline, weekly for 1st 4 weeks then biweekly for last 4 weeks
Notes	Study start date: not reported Study end date: not reported Source of funding: "this study was supported by an investigator‐initiated research grant from Lilly Research Laboratories. Olanzapine and matching placebo were supplied by Lilly Research Laboratories" Conflicts of interest: "Dr Hollander serves on the advisory board of Abbott, Wyeth, Solvay, Somaxon Pharmaceuticals and receives research grants from Lilly, Abbott, Pfizer, UCB‐Pharma, and OrthoMcNeil Pharmaceuticals. All other authors have no financial relationships to disclose". Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided except for, quote: "Patients were evaluated weekly for the first 4 weeks and biweekly for the next 4 weeks in a double‐blind fashion by the treating psychiatrist."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Paper reports that a secondary outcome is the Overt Aggression Scale irritability and aggression subscales however scores are not reported (only P values and z scores)
Incomplete outcome data (attrition bias) All outcomes	High risk	Available data from this relatively small sample of 11 participants (6 treatment and 5 control), we used mixed regression analysis to assess differences in the improvement ratings between the treatment and control groups. This analysis did not eliminate participants, but instead estimated effects using the data available for each participant. The reasons for missing data were children who discontinued the study before 8 weeks and missed treatment visits.
Selective reporting (reporting bias)	High risk	Quote: "The Overt Aggression Scale as listed as one of the outcome measures", however, "we did not find any evidence for significant change on the CYBOCS, the OAS‐M [Overt Aggression Scale‐Modified] irritability measure, or the OAS‐M [Overt Aggression Scale ‐ Modified] aggression measure".
Other bias	High risk	Both active treatment and placebo supplied by the same pharmaceutical company that financially supported the study