Tannock 1992.

Study characteristics
Methods	Cross‐over trial with 3 interventions: LD‐MPH HD‐MPH placebo Phases: 3 separate drug conditions: placebo, LD (0.3 mg/kg) and HD (1.0 mg/kg) medication, with 2 test sessions each. Drug conditions changed on a daily basis: 6 test sessions plus baseline practice session
Participants	Number of participants included: 26 (24 boys, 2 girls) Number of participants followed up: 23 Number of withdrawals: 3 Diagnosis of ADHD: DSM‐III (subtype not stated) Age: mean 9.2 years (range not stated) IQ: mean 105.9 (SD 10.5) MPH‐naive (not clear; "9 children receiving stimulant medication prior to the present study") Ethnicity: not stated Country: Canada Setting: hospital/outpatient department Comorbidity: n = 12, oppositional disorder: 5, oppositional and CD: 3, oppositional and separation anxiety disorder: 1, oppositional and CD and major depression: 2, oppositional and CD and avoidant disorder: 1. Comedication: not clear Other sociodemographics: none Inclusion criteria Diagnosis of ADHD confirmed Child had to be scheduled to receive a trial with MPH independent of the present investigation Exclusion criteria WISC‐R: < 80 Exclusive DSM‐III diagnosis of CD or an emotional disorder Major neurological, physical or sensory impairment
Interventions	Participants were randomly assigned to different drug condition orders of 3 possible interventions: LD‐MPH, or HD‐MPH, and placebo Mean MPH dosage: N/A (modal dose at 0.3 mg/kg = 7.5 mg (range 5.0 mg‐15 mg), modal dose at 1.0 mg/kg = 27.5 mg (range 17.5 mg‐47.5 mg)) Administration schedule: daily single dose Duration of each medication condition: 1 day Washout before trial initiation: 48 h before trial initiation Medication‐free periods between interventions: no Titration period: none Treatment compliance: capsules administered by project staff
Outcomes	General behaviour Wisconsin Card Sorting Test: observer, daily, 90 minutes after treatment Non‐serious AEs Decreased cognitive flexibility (repetitive actions with obsessive quality) Movement stereotypes Facial motor tics Topic perseveration Excessive pre‐occupation with the task at hand and persistent talkativeness: observer, during test session Treatment‐emergent side effects conducted routinely during medication trial in our laboratory Monitored throughout sessions 3 children exhibited unusual side effects leading to trial termination. One exhibited hypersensitivity (skin rash, urticaria and throat clearing), and 2 became somewhat disoriented and confused and complained of odd sensations in their limbs
Notes	Sample calculation: no Ethics approval: not stated Key conclusion of trial authors Results indicate that MPH increased perseverative errors on the first assessment but decreased them on the second; clinical symptoms of perseveration occurred at both assessments. Findings suggest that MPH may reduce cognitive flexibility temporarily in some children with ADHD Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes, child had to be scheduled to receive a trial with MPH independent of the present investigation Any withdrawals due to AEs: yes; 3 Funding source: grant from the Canadian Psychiatric Research Foundation and a Post‐Doctoral Fellowship by the Ontario Mental Health Foundation. Email correspondence with trial authors: April 2014. We emailed trial authors twice to ask for supplemental information/data but have not received a response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not clear
Allocation concealment (selection bias)	Low risk	Double‐blind, placebo‐controlled design. Drug order for the first 3 test sessions was randomly assigned, and each child retained the same order for the remaining 3 sessions
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, placebo‐controlled design. Medication packaged in coloured gelatin capsules to avoid detection of dose and taste. Each child followed the same routine for every test session
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not clear
Incomplete outcome data (attrition bias) All outcomes	High risk	Incomplete outcome data for 3 respondents with unusual side effects Selection bias (e.g. titration after randomisation → exclusion): exclusion due to AEs
Selective reporting (reporting bias)	Unclear risk	No information presented on numbers of participants with side effects or outcomes for data on nausea, BP, etc.