Tannock 1995b.

Study characteristics
Methods	Cross‐over trial with 4 interventions: MPH (0.3 mg/kg, 0.6 mg/kg, 0.9 mg/kg) placebo Phases: washout, baseline, trial 2 groups, ADHD and ADHD + anxiety ‐ were subjected to the same trial
Participants	Number of participants screened: 50 Number of participants included: 40 (34 boys, 6 girls) Number of participants followed up: 40 Number of withdrawals: none Diagnosis of ADHD: DSM‐III‐R (no subtype) Age: ADHD mean 9.4; ADHD + anxiety mean 9.1 (range 7‐11 years); IQ: > 80 MPH‐naive: not stated Ethnicity: white (90%), African American or Asian (10%) Country: Canada Setting: outpatient clinic Comorbidity (type: overanxious 27.5%, separation anxiety 5%, over anxiety and separation anxiety 10%, avoidant disorder with overanxious traits 2.5%, ODD 55%, CD 10%) Comedication: not stated Other sociodemographics: predominantly from middle‐class families Inclusion criteria Meeting DSM‐III‐R criteria At least 2 of the following ≥ 15 on the Conners' Abbreviated Symptom Questionnaire ≥ 4 inattentive, 4 impulsive and 3 hyperactive symptoms rated as "pretty much" or "very much" on SNAP Questionnaire Score of 5 or 6 on the Hyperactivity factor of the Rutter Child Scales Exclusion criteria Full scale IQ < 80 Evidence of major neurological, physical or sensory impairment Medical or neurological contraindications for stimulant medication Not knowing the number facts of 10. Needing to use concrete materials (i.e. fingers) to add numbers Inclusion criteria for the ADHD + anxiety group ≥ 1 of the following DSM‐III‐R criteria for overanxious, separation anxiety or avoidant disorder based on parent interview Score > 1 SD above the mean for age and sex on the Revised Children’s Manifest Anxiety Scale Score > 1 SD for age and sex on the Trait Scale‐C2 of the State‐Trait Anxiety Inventory for Children Children in the ADHD group did not meet any of these criteria for anxiety
Interventions	Participants were randomly assigned to 1 of 12 possible drug condition orders of 0.3 mg/kg, 0.6 mg/kg or 0.9 mg/kg MPH and placebo Mean MPH dosage: 0.3 mg/kg = 8.75 (± 2.2); 0.6 mg/kg = 17.75 (± 4.2); 0.9 mg/kg = 27.25 (± 5.6) Administration schedule: once/d Duration of each medication condition: 1 day Washout before trial initiation: 48 h when applicable Medication‐free period between interventions: not stated Titration period: no, but there was a 1‐day open trial on 0.3 mg/kg before proceeding to ascertain tolerance Treatment compliance: medication was administered at the laboratory
Outcomes	Non‐serious AEs Heart rate and radial pulse, once at baseline and 3 times during each session
Notes	Sample calculation: not stated Ethics approval: not stated Key conclusion of trial authors "High levels of trait anxiety in children with ADHD predict poor (but not adverse) response to methylphenidate in terms of working memory, and add to growing evidence that ADHD with anxiety constitutes a distinct and clinically meaningful subtype of ADHD." Comment from review authors Main trial was preceded by a 1‐day trial of the lowest dose to assess tolerance to MPH Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; see above Any withdrawals due to AEs: no Funding: in part by the Ontario Mental Health Foundation and the National Health Research and Development Program, Health Canada Email correspondence with trial authors: June 2014. Emailed trial authors twice to request supplemental information/data but have received no response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Drug order was counterbalanced and determined by random assignment, such that an approximately equal number of children were assigned to each of 12 possible orders
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Active medication and placebo were prepared by the hospital pharmacy, packaged in identical opaque gelatin capsules and administered in a double‐blind manner
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): 1‐day open trial to assess tolerance before main trial, but no children were excluded
Selective reporting (reporting bias)	Low risk	All outcomes are reported