Butter 1983.

Study characteristics
Methods	1‐week, double‐blind, parallel trial with 3 arms: adrenocorticotropic hormone MPH (10 mg, 15 mg or 20 mg, weight‐adjusted) placebo
Participants	Number of participants screened: not stated Number of participants included: 30 (all boys) Number of participants followed up: MPH 10, placebo 10 Diagnosis of ADHD: DSM‐III Age: mean not stated (range 6‐12) IQ: > 85 MPH‐naive: not stated Ethnicity: not stated Country: Canada Setting: outpatient clinic Comorbidity: not stated Comedication: not stated Other sociodemographics: no information about significant differences in baseline demographics between groups Inclusion criteria Clinical ADHD diagnosis of ADD with hyperkinesis (DSM‐III) Hyperkinesis rating required a score of ≥ 15 on Short Form CRS, and hyperkinetic behaviour had to be apparent throughout most of the day Untreated behaviour had to be a cause of severe difficulty both at home and at school Exclusion criteria WISC score < 85 or abnormal perceptual functioning
Interventions	Participants were randomly assigned to adrenocorticotropic hormone, MPH or placebo Number of participants randomly assigned to each group: adrenocorticotropic hormone 10, MPH 10, placebo 10 Mean MPH dosage: 0.5 mg/kg Administration schedule: once daily, 7.30 am Duration of intervention: 1 week. 1 week drug‐free followed by 1 week of placebo treatment. After placebo washout, randomly assigned to adrenocorticotropic hormone, MPH or placebo Titration period: none Treatment compliance: not stated
Outcomes	ADHD symptoms Short Form CRS: completed by parents and clinicians CTRS: rated during placebo and active drug phases Non‐serious AE EEG, haematology, liver and kidney function test, BP and pulse, blood chemistry, urinalysis before and after treatment EEG, haematology, blood chemistry and urinalysis were within normal limits before treatment and remained so after treatment
Notes	Sample calculation: not stated Ethics approval: not stated Key conclusion of trial authors Children treated with MPH show significantly greater vasomotor reactivity, behavioural improvement and learning receptivity than children treated with adrenocorticotropic hormone and placebo Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: no Funding source: the Scientific Development Group, Organon International B.V., Oss, the Netherlands
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	After placebo washout, treatment was assigned in a double‐blind and random manner
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blind
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Neurologist assessing EEG blinded. Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol identified