Bedard 2008.

Study characteristics
Methods	4‐day randomised, double‐blind, placebo‐controlled, cross‐over trial with 2 interventions in 2 groups MPH placebo and ADHD with anxiety ADHD without anxiety
Participants	Number of participants screened: not stated Number of participants included: 130 Number of participants followed up: 130 (110 boys, 20 girls) Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV (combined (63%), hyperactive‐impulsive (30%), inattentive (6%)) Age: mean 9 years (SD 1.46, range 6‐12) IQ: mean 104.11 MPH‐naive: 70% Ethnicity: white (90%) Country: Canada Setting: outpatient clinic Comorbidity: specific learning disorder (34%), CD (24%), ODD (26%), generalised anxiety disorder (17%), separation anxiety disorder (11%) Comedication: not stated Other sociodemographics: none Inclusion criteria DSM‐IV diagnosis via clinical diagnostic assessment: confirmed by PICS and TTI Exclusion criteria IQ < 80 Evidence of neurological dysfunction, poor physical health or uncorrected sensory impairments History of psychosis based on physician enquiry Primary language spoken at home not English
Interventions	Participants were randomly assigned to 1 of 11 possible drug condition orders of MPH and placebo. Children weighing < 25 kg received 5 mg, 10 mg and 15 mg of MPH; children weighing ≥ 25 kg received 10 mg, 15 mg and 20 mg of MPH Mean MPH dosage: 0.28 mg/kg, 0.45 mg/kg, 0.61 mg/kg Administration schedule: not stated Duration of each medication condition: 1 day, 3 days of MPH in all Washout before trial initiation: none Medication‐free period between interventions: not stated Titration period: none Treatment compliance: not stated
Outcomes	ADHD symptoms IOWA‐CRS completed by the examiner at the end of each session
Notes	Sample calculation: no Ethics approval: approved by the institutional ethics review board Comment from trial authors We cannot predict that similar results would hold with longer‐term treatment or with extended‐release preparations Key conclusions of trial authors Findings provide insight into potential mechanisms underlying individual differences in treatment response in ADHD, which may facilitate more targeted treatments Results from the present trial demonstrate that MPH produces moderate but beneficial effects on selected aspects of working memory that are known to be impaired in ADHD. Furthermore, comorbid anxiety may be a predictor of working memory treatment response 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: Funding and operating grant from the Canadian Institute of Health Research and funding from the Canada Research Chairs Programme Email correspondence with trial authors: December 2013. Not able to get supplemental information from trial authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Master randomisation tables were prepared by the research support pharmacist at the hospital by using simple randomisation with restrictions (high dose not to be given on the first possible drug day nor immediately following placebo; no directly ascending or descending dose order). Therefore, a balanced block 22 design was used
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Examiner, psychiatrist, participant and participant’s family were not informed about participant’s randomisation order or daily medication status until completion. Placebo and active medication were prepared by the hospital pharmacist and were powdered and packaged in an opaque capsule to prevent identification of contents by colour, taste or volume
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Trained clinicians, blinded to other aspects of the participant’s assessment, conducted interviews independently
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol available