Buitelaar 1990.

Study characteristics
Methods	4‐week crossover trial of adrenocorticotrophic hormone (synthetic analog of ACTH 4‐9 (Org 2766)) versus placebo
Participants	Inclusion criteria: children 5‐13 years outpatients from the Department of Child Psychiatry of the Utrecht University Hospital met the DSM‐4 criteria for infantile autism full syndrome, or for atypical PDD Exclusion criteria: "patients who suffered from gross neurological disorders, and internal and endocrinological diseases were excluded". Location/setting: child psychiatry outpatient clinic at Utrecht university hospital, The Netherlands Sample size: 14 Number of withdrawals/ dropouts: none reported Gender: 12 male, 2 female Mean age: 8.5 years IQ: Group 1 (Org 2766/ placebo): 65.3; Group 2 (placebo/Org 2766): 62.3 Concomitant medications: not reported History of previous medications: not reported Baseline ABC‐I scores or other BoC: parent‐rated ABC‐I: 9.4 (6.8) Exclusion criteria included "having gross neurological disorders, and internal and endocrinological diseases; used psychotropic, or had used anticonvulsive or related medications 3 months prior to or during the trial".
Interventions	Adrenocorticotrophic hormone (4‐9) for 4 weeks: Org 2766 was given at 20 mg/day for 4 weeks, after a 2‐week placebo period Placebo for 4 weeks: equivalent placebo
Outcomes	Primary outcomes: irritability, measured using the ABC‐Irritability subscale (Aman 1985) Secondary outcomes: none reported Timing of outcome assessment: baseline, after intervention phase and after placebo phase
Notes	Study start date: not reported Study end date: not reported Funding source: not reported Conflicts of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient details provided
Allocation concealment (selection bias)	High risk	Tablets of Org 2766 or identical matching placebo tablets were provided by Organon International B.V. and labelled by the local pharmacy. Assignment to treatment order occurred at random
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "During the trial the behavior of the child was rated once every 2 weeks at home by the parents or caretakers, and at school or day care unit by teacher or nurse".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All children completed the trial however Quote: "because of intermittant physical illness one child could not visit his day care unit for several periods of time. Behaviour checklist ratings from teachers were dismissed for this child".
Selective reporting (reporting bias)	Low risk	The primary outcome measures were play observations and the ABC (all subscales), which were all measured and reported in full.
Other bias	High risk	Tablets of Org 2766 and identical matching placebo tablets were provided by Organon International B.V.