Swanson 1999.

Study characteristics
Methods	4 week, double‐blind, randomised, cross‐over trial with 4 interventions of each 1 day duration MPH twice/d: 2 doses of IR‐MPH 4,5 h apart MPH Flat: morning dose of 80% twice/d morning dose and the rest at 30‐minute intervals over 6 h, starting 1.5 h after first dose MPH Ascending: morning dose of 40% twice/d morning dose and that rest as increasing doses at 30‐min intervals over 5 h, starting 1.5 h after 1st dose Placebo
Participants	Number of participants screened: not stated Number of participants included: 38 (33 boys, 5 girls) 4 withdrew before randomisation and 34 were included in the cross‐over trial Number of participants followed up: 31 Number of withdrawals: 3 Diagnosis of ADHD: DSM‐IV (subtype not stated) Age: mean 9.2 years (range 7‐12) IQ: not stated MPH‐naive: 0% Ethnicity: not stated Country: USA Setting: outpatient clinic (laboratory classroom) Comorbidity: not stated Comedication: not stated Other sociodemographics: none Inclusion criteria Diagnosis of ADHD Onset by 7 years of age Receiving current treatment with MPH doses of 5‐15 mg administered 2 or 3 times/d 7 to 12 years of age Exclusion criteria Not stated
Interventions	Participants were randomly assigned to different drug condition orders of 4 different interventions: MPH twice/d, flat and ascending, and placebo Mean MPH dosage: not stated. Nominal dose: 20 mg/d Administration schedule: 30‐min intervals from 7:30 am to 3:00 pm Duration of each medication condition: 1 day Washout before trial initiation: none Titration period: none (participants were kept on current standard treatment between trial days) Treatment compliance: not stated
Outcomes	ADHD symptoms SKAMP: teacher‐rated, 4 times during the day CLAM: teacher‐rated, 4 times during the day
Notes	Sample calculation: no Ethics approval: yes Comment from trial authors Of the 38 children recruited for this trial, only 34 entered Key conclusion of trial authors Acute tolerance to MPH appears to exist Comment from review authors Publication includes 2 studies: in study I, relative efficacy was determined for 3 dosing patterns of MPH vs placebo. In study II, tolerance was assessed by comparison of 3‐times‐a‐day regimens of MPH only. The latter is not part of the data extraction Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes, only participants on a stable dose of MPH were included Any withdrawals due to AEs: unclear. No information about withdrawals given Funding: ALZA Corporation, Palo Alto, California Email correspondence with trial authors: May 2014. Emailed trial authors to ask for additional information. No reply has been received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"On subsequent Saturdays, each child received (in random order) 1 of 3 possible drug condition orders of MPH and placebo"
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All treatments were administered in identical capsules
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	High risk	Only completers were followed up Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): unclear, no information about withdrawals
Selective reporting (reporting bias)	Unclear risk	No protocol was published.