Tirosh 1993b.

Study characteristics
Methods	Double‐blind, controlled, cross‐over trial with 2 interventions: MPH placebo
Participants	Number of participants screened: unknown Number of participants included: 11 (8 boys, 3 girls) Number of participants followed up: 10 Number of withdrawals: 1 Diagnosis of ADHD: DSM‐III (subtype not stated) Age: median 9 years 8 months (range 6.9‐12.3 years) IQ: median 106 (range 92‐118) MPH‐naive: 100% Ethnicity: not stated Country: Israel Setting: outpatient clinic Comorbidity: none Comedication: none Other sociodemographics: low middle class (n = 2), middle class (n = 8) Inclusion criteria Healthy; no neurological deficit Living with their natural parents Medication‐naive Exclusion criteria Not stated
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of 0.3 mg/kg to 0.4 mg/kg MPH (total dose 10 mg‐15 mg) and placebo Mean MPH dosage: 0.3 mg/kg‐0.4 mg/kg Administration schedule: once daily at 7:30 am on 6 of the 8 days. During the other 2 days, a second dose was administered at 2:00 pm Duration of each medication condition: 8 days Washout before trial initiation: not stated Medication‐free period between interventions: 3 days Titration period: none Treatment compliance: as measured by returned package pill counts, this was rated as full compliance for the 10 children remaining in the trial
Outcomes	ADHD symptoms CTRS and CPRS: before therapy and after each intervention Non‐serious AEs Sleep measurements, 10 min before "lights out" until morning awakening for 4 successive nights during each of the 3 respective periods
Notes	Sample calculation: no Ethics approval: not stated Key conclusions of trial authors Results support the notion that ADHD is a centrally generated disorder attributable to hypoarousal, which subsequently stimulates motor overactivity MPH does not appear to affect sleep patterns adversely and possibly normalises them in individuals with ADHD Comment from review authors No useful data Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: yes; 1 Funding source: not declared Email correspondence with trial authors: December 2013. We were unable to receive supplemental data from trial authors because the trial is 20 years old (Ramstad 2013d [pers comm]).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	A drug‐placebo sequence was used for children assigned odd numbers in the trial and vice versa
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Look‐alike placebo tablets were supplied
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigator who analysed the data was unaware of the drug‐placebo sequence
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol available