NCT02293655.

Study characteristics
Methods	A 4‐week parallel discontinuation trial with 2 arms: MPH discontinuation (placebo) MPH at optimised dosage
Participants	Number of participants screened: 204 Number of participants included: 109 (72 boys, 37 girls) Number of participants followed up: 100 Number of withdrawals: 9 (no reason given) Diagnosis of ADHD: DSM‐5 (type not stated) Age: range 7‐11 IQ: < 80 MPH‐naive: not stated Ethnicity: Hispanic or Latino (n = 9), not Hispanic or Latino (n = 100). Race: white (n = 88), more than one race (n = 10), black or African American (n = 8), Asian (n = 3) Country: USA Setting: outpatient Comorbidity: not stated Comedication: all psychiatric medications were exclusion criteria Additional sociodemographics: none Inclusion criteria ADHD diagnostic status: meets DSM‐5 criteria for ADHD, with CGI rating corresponding to at least "moderately ill." Cognitive and academic functioning: IQ of > 80 as estimated by Vocabulary and Block design subtests of the WISC‐IV and scaled scores > 80 on the Wechsler Individual Achievement Test‐2nd Edition Reading and Math subtests Physical health: physical exam and ECG findings are judged to be normal for age and sex by trial physician and/or medical consultant, and there is no co‐existing condition for which MPH is contraindicated School: enrolled in a school setting rather than a home‐school program. This ensures that they can obtain parent and teacher ratings from separate individuals for diagnosis and outcome assessment Exclusion criteria Psychiatric medications: current or prior use of any medication for psychological/psychiatric problems Behavioral interventions: current active participation in ADHD‐related behavioral interventions, given that improvements due to these interventions may confound our group comparisons Psychiatric or neurobehavioral conditions: children with mania/hypomania, schizophrenia, or severe depressive disorder, as determined by the K‐SADS, will be excluded since ADHD medications may not be an appropriate first line of treatment for children with these comorbid disorders Organic brain injury: history of head trauma, neurological disorder (including epilepsy), or other disorder affecting brain function due to potential differences in neurophysiology of ADHD phenotype Cardiovascular risk factors: children with a personal history or family history of cardiovascular risk factors will be excluded, or given the option of participating in the trial after obtaining an ECG and verification from a paediatric cardiologist regarding the safety of their participation in a trial of MPH. In this case, families will be responsible for the costs of ECG and any necessary cardiologist evaluation Pregnancy: the safety of MPH use during pregnancy has not been established
Interventions	Participants were randomly assigned to either discontinue MPH (and receive placebo) or remain on optimal dose of MPH (OROS‐MPH) for 4 weeks. Number randomised to each group: MPH = 17, placebo = 92 Mean medication dosage: not stated Administration schedule: once daily Duration (of (each) medication): 4 weeks Washout before trial initiation: none Medication‐free period between interventions: none Titration period: 4‐week placebo controlled MPH titration trial before randomisation (followed by a 4 weeks of maintenance phase at optimal dosage) Treatment compliance: not stated, but according to the protocol compliance will be elaborated at each visit
Outcomes	ADHD symptoms Parent Vanderbilt ADHD‐RS Total Symptom Score Serious AEs C‐SSRS General behavior Behavior Rating Inventory of Executive Function (BRIEF) scales Non‐serious AEs Pittsburg Side Effect RatingScale CSHQ All outcomes assessed at baseline, during the maintenance period and 3 times during the discontinuation trial on/around day 1, 14 and 28 Only the Parent Vanderbilt ADHD‐RS Total Symptom Score and prevalence of side effect data were available for the review
Notes	Sample calculation: not stated Ethics approval: not stated Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH: yes; participants were only randomised if they completed the dose titration and maintenance phases Any withdrawals due to AEs: not stated Funding source: Children's Hospital Medical Center, Cincinnati
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information on method of sequence generation
Allocation concealment (selection bias)	Unclear risk	No information on method of allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"With blinded randomisation during MPH titration Trial and Discontinuation Phase (through use of over‐encapsulated medication and identical placebos), the entire trial will be triple‐blind (i.e., participant families, trial staff, and teachers will be blinded to medication and dose)"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"With blinded randomisation during MPH Titration Trial and Discontinuation Phase (through use of over‐encapsulated medication and identical placebos), the entire trial will be triple‐blind (i.e., participant families, trial staff, and teachers will be blinded to medication and dose)"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information regarding reason for withdrawals and method of analysis Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): not stated
Selective reporting (reporting bias)	High risk	All outcomes have not been published yet