Rapport 2008.

Study characteristics
Methods	Double‐blind, placebo‐controlled, 5‐week, cross‐over trial with 2 interventions: MPH (5 mg, 10 mg, 15 mg and 20 mg) placebo Phases: baseline (1 week) and 5 cross‐over phases (1 week placebo and 1 week MPH each)
Participants	Number of participants screened: not stated Number of participants included: 65 Number of participants followed up: 65 (58 boys, 7 girls) Number of withdrawals: none Diagnosis of ADHD: DSM‐IV (all were of the combined subtype) Age: mean 8.56 years (SD 1.25; range 6‐11) IQ: mean 102.8 (SD 10.0; range not stated) MPH‐naive: 8 had experienced brief trials of stimulant therapy within the previous 4 years. None were prescribed psychostimulants immediately before the start of the current trial Ethnicity: white (100%) Country: USA Setting: outpatient clinic Comorbidity: not stated Comedication: not stated Other sociodemographics: low to middle Inclusion criteria ADHD diagnosis confirmed by the K‐SADS Problems in ≥ 50% of the situations on the Barkley Home Situations Questionnaire Maternal rating ≥ 2 SD above the mean on the Werry‐Weiss‐Peters Activity Scale Teacher rating on the ADD/H Comprehensive Teacher Rating Scale ≥ 2 SD above the mean Exclusion criteria CD; gross neurological, sensory or motor impairment
Interventions	Participants were randomly assigned to different possible drug condition orders of IR‐MPH (5 mg/d, 10 mg/d, 15 mg/d, 20 mg/d) and placebo Mean MPH dosage: not stated Administration schedule: once daily, in the morning Duration of each medication condition: 1 week Washout before trial initiation: none were prescribed psychostimulants immediately before the start of the current trial Medication‐free period between interventions: 1 day Titration period: none Treatment compliance: "nearly 100%; envelopes were returned on a weekly basis"
Outcomes	Non‐serious AEs Subject's Treatment Emergent Symptoms Scale of NIMH (adjusted to children for the children): rated weekly by observer interviewing parent and child
Notes	Sample calculation: not stated Ethics approval: yes Comments from trial authors Increased frequency and/or severity of emergent symptoms reported by or observed in children receiving psychostimulant therapy are probable to the extent that dosing regimens differ from the parameters reported herein, particularly for symptoms highly specific to MPH, that is, children receiving multiple doses per day, single doses exceeding 20 mg, different MPH formulations and MPH over a longer duration of time are likely to experience greater frequency and/or severity of emergent symptoms IR‐MPH formulary is currently used less frequently than that of newer formulations, and the generalisability of present findings to long‐duration, ER and other variants is unknown Key conclusion of trial authors "Collectively, our findings point to a clear need to develop psychometrically sound treatment‐emergent symptom rating scales for the purposes of monitoring physical and behavioural complaints of children treated with psychostimulants" Comment from review authors Trial authors used a design with a once‐daily, IR‐preparation of MPH. This seems to be exceptional compared with other studies Inclusion of MPH responders only/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: none Email correspondence with trial authors: April 2014. Obtained supplemental information regarding data (Ramstad 2013c [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	By email: "we used a computer‐generated random assignment (without replacement) procedure with an additional stipulation that a nearly equal number of children had to be assigned to each of the possible drug condition orders. Children were entered onto the list as they entered the trial and followed that particular order (of which coders, parents, teachers and evaluators were unaware throughout the trial)" (Magnusson 2014b [pers comm])
Allocation concealment (selection bias)	Low risk	Same as above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	MPH and placebo dosages were packaged in coloured gelatin capsules by the clinic's pharmacist to avoid detection of dose and taste
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Rater was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Information received by email: no dropouts (Magnusson 2014b [pers comm]) Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	No indication of selective reporting. All outcomes were reported