Martins 2004.

Study characteristics
Methods	4‐week, double‐blind, randomised, parallel trial with 2 interventions: MPH group: MPH, 7 days a week placebo group: MPH Monday through Friday, and placebo on weekends
Participants	Number of participants screened: not stated Number of participants included: 40 (all boys) Number of participants followed up: 38 Number of withdrawals: 2 (receiving MPH) Diagnosis of ADHD: DSM‐IV (combined (92.5%)) Age: mean MPH 9 years (SD 2.2, range 6‐14), placebo 9.6 years (SD 2.8, range 6‐14) IQ: mean, MPH 97.3, placebo 93.5 MPH‐naive: not stated Ethnicity: European‐Brazilian: MPH 16 (76.2%), placebo 15 (78.9%) Country: Brazil Setting: outpatient clinic Comorbidity: yes; conduct or ODD (MPH 57.2%, placebo 57.9%) Comedication: not stated, no psychiatric medication Other sociodemographics: monthly family income was calculated according to the following formula: total monthly income received by all members of the family (expressed in number of minimum wages) divided by the number of people in the family. A value lower than 0.7 (approximately USD 68 per family member per month) is usually an indicator of poverty in Brazil. MPH 3.3, placebo 2.4. No significant differences in baseline demographics were noted between the 2 groups Inclusion criteria ADHD diagnosis according to DSM‐IV criteria Between 6 and 14 years of age Male Education level between 1st and 8th elementary grades Exclusion criteria Presence of significant neurological or clinical disease Presence of bipolar disorder or substance abuse/dependence disorder Use of any psychiatric medication in the past 6 months, including MPH Estimated IQ < 70
Interventions	Participants were randomly assigned to MPH 7 d/week or to MPH on weekdays and placebo on weekends Number randomised to each group: MPH 21, placebo 19 Mean MPH dosage: initial dose of MPH was 0.3 mg/kg/d the 1st week. Dose was raised to 0.5 mg/kg/d the 2nd week and to 0.70 mg/kg/d the 3rd and 4th weeks Administration schedule: twice/d: breakfast and lunch Duration of intervention: 4 weeks Titration period: none Treatment compliance: only 7 of 160 blister packs were returned with unused pills
Outcomes	ADHD symptoms 10‐item CARS (Conners 1985). Rated every Monday after school by both teachers and parents Serious AEs Barkley Side Effect Rating Scale Number of AEs reported Mean severity of reported AEs (Completed only by parents for assessment of side effects on weekends)
Notes	Sample calculation: no Ethics approval: approved by the Ethical Committee of the Hospital de Clínicas de Porto Alegre (HCPA) (approved as an International Review Board (IRB) by the Office for Human Research Protections, USA) Comments from trial authors Context established by the home setting on the weekend may have created conditions in which the effects of MPH were minimal or insignificant, because children may have been involved in play activities much of the time It is reasonable to suggest that during the weekend, when networks related to ADHD neurobiology might be demanded less often, differences between drug and placebo would be more difficult to detect It is possible that parental tolerance of ADHD symptoms on weekends might be greater than on weekdays. Our findings may not be generalisable to female patients Key conclusion of trial authors "Our findings suggest that weekend holidays during MPH administration reduce the side effects of insomnia and appetite suppression without causing a significant increase in ADHD symptoms, on weekends or on the first day of school after the weekend (Monday)" 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: MPH and placebo pills were supplied by Novartis Pharmaceuticals (São Paulo, Brazil) at no cost and without restrictions. No additional funding was requested or received from Novartis or any other commercial entity Email correspondence with trial authors: we have contacted trial authors several times to ask for additional information about data, but we have received no data from this trial that we can use
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised, double‐blind, parallel‐group design was used. Participants were randomly assigned to 1 of 2 groups, according to a computer‐derived algorithm (EPIINFO.06)
Allocation concealment (selection bias)	Low risk	Computer‐derived algorithm
Blinding of participants and personnel (performance bias) All outcomes	Low risk	MPH and placebo pills were of the same shape and colour
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind. No other information
Incomplete outcome data (attrition bias) All outcomes	Low risk	Measured adherence to protocol by assessing returned, unopened blister packs. None of the findings in the analyses was significantly affected by the 2 participants (they did not follow the protocol as stated by researchers) from the MPH group who did not receive a few doses appropriately on weekends or on Monday. Some teacher ratings (8.5%) were missed because of the child’s absence from school on a specific day of evaluation or because of a school holiday 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 reporting bias