Konrad 2004.

Study characteristics
Methods	Double‐blind, placebo‐controlled, within‐participant trial of cross‐over design, lasting 6 days with 2 possible drug interventions and placebo: MPH 0.25 mg/kg (LD) MPH 0.5 mg/kg (HD) placebo The order of drug conditions was randomly assigned, with the restriction that higher doses should never be administered after placebo
Participants	Number of participants screened: not stated Number of participants included: 60 (44 boys, 16 girls) Number of participants followed up: 60 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV (combined 47 (78%), inattentive 13 (22%)) Age: mean 10.8 years (SD 1.6, range 8‐12) IQ: mean 97.4 (SD 10.7, range not stated) MPH‐naive: 100% Ethnicity: not stated Country: Germany Setting: outpatient clinic and inpatient ward Comorbidity: ODD (n = 6; 10%), CD (n = 18; 30%), anxiety (n = 12; 18%), dyslexia (n = 19; 32%) Comedication: no Other sociodemographics: no significant differences in baseline demographics were noted between the 2 groups Inclusion criteria Only children without a prior history of stimulant treatment were included in the trial protocol Exclusion criteria General IQ < 80 (WISC‐III) Any potentially confounding diagnoses such as psychosis, mania, major depression, substance abuse, pervasive developmental disorders, receptive language disorders Use of any kind of additional medication (including SSRIs or anticonvulsants)
Interventions	Participants were randomly assigned to "low‐dose" MPH (0.25 mg/kg), "high‐dose" MPH (0.5 mg/kg) and placebo Number randomised to each group: LD‐MPH 60; HD‐MPH 60; placebo 60 Mean MPH dosage: 9.2 mg (SD 2.2) for LD group (0.25 mg/kg), 18.4 mg (SD 5.4) for HD group (0.5 mg/kg) Administration schedule: medication was given between 7:00 am and 8:00 am for 6 days. "Cognitive testing began 60 minutes after medication ingestion and lasted 80 minutes". The order of drug conditions was randomly assigned, with the restriction that higher doses should never be administered after placebo. Thus, 11 orders were possible for the 6‐day procedure as a whole, and 6 orders were possible for the sequence of the 3 neuropsychological assessments. Children were assigned in equal numbers to the 6 orders Duration of intervention: 6‐day intervention, with each child receiving each intervention for 2 random days Titration period: before randomisation, 1 week of 0.3 mg/kg MPH for each participant "to ascertain tolerance" Treatment compliance: not stated
Outcomes	ADHD symptoms Primary outcomes German Teacher’s and Parental Report on ADHD symptoms (Fremdbeurteilungsbogen für Hyperkinetische Störungen) Parental questionnaire on ADHD symptoms (Diagnostiksystem für Psychische Störungen im Kindes‐ und Jugendalter nach ICD‐10 und DSM‐IV) CBCL Specific attentional outcome measures Baseline speed: assessed with a simple reaction time task Sustained attention: involved the continuous and consecutive presentation of 50 series of 12 different dot patterns (600 signals) Focused attention: 4 letters were presented simultaneously, and the child was instructed to respond with the 'yes' key to 1 target letter, but only if this occurred in 1 of the relevant diagonal positions Divided attention: dual task that combined optic and acoustic discrimination tasks Stop‐Signal paradigm: the 'go' task in our stop‐signal task was a choice reaction task in which an unidentified flying object (UFO) appeared to the left or right of a fixation cross Visual set‐shifting: task consisted of 3 parts
Notes	Sample calculation: not stated Ethics approval: yes; "the study was approved by the Medical Ethical Committee of the University Hospital of Aachen" Comments from trial authors The present trial investigated effects of day‐to‐day medication on attentional functions, which might differ from dose‐dependent effects in the long run "Our trial did not include a third methylphenidate dose, which would have allowed additional trial of dose‐response curves for higher doses of methylphenidate" Key conclusions of trial authors Results indicate that attentional functions are influenced differentially by MPH; intensity‐dimension functions are best influenced by higher doses, executive functions by moderate doses and selectivity‐dimension functions by variable doses Divergent results from behaviour rating scales and from attentional paradigms emphasise that clinicians have to decide what constitutes an appropriate clinical response A more comprehensive assessment of attention may help to reveal an individually optimal dose for the treatment of attentional dysfunction Comment from review authors This study focuses on aspects of attention in relation to MPH Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes, before testing, all children were given 0.3 mg/kg MPH each day for ≥ 1 week to ascertain tolerance Any withdrawals due to AEs: not stated Funding source: German Society for the Advancement of Scientific Research (DFG grant KFO112) Email correspondence with trial authors: January 2014. We sent an email to the trial author to request additional information but have not received a reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Within the 6‐day protocol, the order of drug conditions was randomly assigned, with the restriction that higher doses should never be administered after placebo
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The active medication and placebo were prepared by a study protocol physician who was not involved in the assessment. All capsules were identical opaque gelatin capsules and were administered in a double‐blinded manner. Capsules containing placebo (lactose) or 0.25 mg/kg or 0.5 mg/kg doses of methylphenidate were prepared for each participant"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	As above
Incomplete outcome data (attrition bias) All outcomes	High risk	"Due to computer problems, data for four children in one task in one condition were missing. As recommended by Tabachnik and Fidell (1996), these data were replaced by the average of the group per condition" 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