Van der Meere 1999a.

Study characteristics
Methods	7‐week, randomised, double‐blind, placebo‐controlled, parallel‐group trial with 3 arms MPH placebo clonidine
Participants	Number of participants screened: not stated Number of participants included: 48 (+24 in the clonidine group not used in this review) (62 boys, 10 girls) Number of participants followed up: 47 (MPH 23, placebo 24) Number of withdrawals: 1 (from the MPH group) Diagnosis of ADHD: DSM‐III‐R (subtype not stated) Age: mean 8.8 years (range 7‐12) IQ: > 70 MPH‐naive: 100% Ethnicity: mainly white Country: the Netherlands Setting: outpatient clinic Comorbidity: CD (11%), ODD (33%), depressive disorder (3%), overanxious disorder (1%), dysthymia (3%), generalised tonic‐clonic seizures (1%), ventricular septal defect (1%), congenital hypothyroidism (1%), precocious puberty (1%), deaf in right ear (1%), atresia in 1 ear (1%) Comedication: yes; for participants who had diseases that required it, for example, hypothyroidism Other sociodemographics: 44% from lower socioeconomic families Differences between groups No significant differences in age and IQ were noted between the 2 groups Inclusion criteria Boys and girls 6‐15 years of age IQ > 70 Living in a family home and attending school DSM‐III‐R diagnosis of ADHD, ADHD symptoms impeding development and psychological/educational treatments with insufficient effect No earlier use of stimulant drugs or clonidine and no psychoactive medications of any kind in the last 6 months No medical contraindications No important changes expected for the course of the trial It was considered clinically meaningful by both parents and the attending physician to try "hyperactivity medication" Exclusion criteria Additional psychoactive drugs during the trial Pervasive developmental disorder or tic disorder. These participants were included in other trial groups.
Interventions	Participants were randomly assigned to MPH, placebo or clonidine Number of participants randomised to each group: MPH 24, placebo 24, clonidine 24 Total oral daily MPH dosage: 0.06 mg/kg Mean of the absolute MPH dose: 9.85 mg (2.26) Administration schedule: breakfast and lunchtime Duration of intervention: 7 weeks Titration: no, but dosage adjustments were made/allowed during first weeks Titration period: none Treatment compliance: maintained and checked by instructions (both oral and written) to both parents and child, and by counting tablets remaining at the end of treatment. Only 1 participant in the MPH group showed poor compliance
Outcomes	ADHD symptoms CTRS: baseline and at week 7 General behaviour Parent and Teacher Versions of the abbreviated Groninger Behaviour Observation Scale (GOO and GBO, respectively): baseline and at weeks 3, 5 and 7 Parent and Teacher Versions of the abbreviated Groninger Behaviour Checklists (GGGS and GGBS, respectively): baseline and at week 7 GPO rating: baseline and at week 7 Non‐serious AEs Parent ratings of drowsiness, insomnia, decreased appetite, nausea, headache, nervousness, motor restlessness, feelings of dizziness, dry mouth, nightmares, apathy, irritability and "other complaints" Child and parents were asked about all kinds of physical and behavioural complaints or changes at trial visits
Notes	Sample calculation: yes (≥ 15 participants in each group) Ethics approval: yes Key conclusion of trial authors "We concluded that the state regulation problem in ADHD is resistant to MPH and clonidine" 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: grants from the Sophia Foundation for Medical Research and Boehringer Ingelheim BV, the Netherlands Email correspondence with trial authors: September 2013. We obtained supplemental information regarding a publication with information about randomisation and supplemental data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The statistician sent the randomisation list to the pharmacist. Participants were then randomly assigned by a research pharmacist. To ensure blinding, pharmacists applied randomisation blocks at random at a length of 2 or 4 participants. MPH and matching placebos were used
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Teacher, parent, clinician, child and experimenter were blind to treatment conditions
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Teacher, parent, clinician, child and experimenter were blind to treatment conditions
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT Selection bias: no, but dosage adjustments were made for several participants because of annoying AEs
Selective reporting (reporting bias)	Low risk	No indication of selective reporting