Barkley 2000.

Study characteristics
Methods	Double‐blind, placebo‐controlled, within‐participant, cross‐over trial with 3 interventions MPH: 5 mg, 10 mg, twice/d amphetamine and dextroamphetamine mixed salts (Adderall): 5 mg, 10 mg, twice/d placebo Phases: 5, but high doses of each stimulant always followed lower dose of the same stimulant
Participants	Number of participants screened: 46 Number of participants included: 38 Number of participants followed up: 35 (30 boys, 5 girls) Number of withdrawals: 2. One was a post hoc exclusion Diagnosis of ADHD: DSM‐IV (subtype not described) Age: mean 14 years (range 12‐17) IQ: mean 103.9 (range 80‐141) MPH‐naive: not stated Ethnicity: not stated Country: USA Setting: outpatient clinic Comorbidity: not stated Comedication: not stated Other sociodemographics: none Inclusion criteria Adolescents, 12‐17 years of age, with a DSM‐IV diagnosis of ADHD Exclusion criteria History of motor or vocal tics, Tourette’s syndrome, cardiac surgery, high BP, cerebral vascular accident, hyperthyroidism or pregnancy or lactation Adverse reactions to stimulant medications
Interventions	Participants were randomly assigned to 1 of 4 possible drug condition orders of 5 mg MPH followed by 10 mg MPH and 5 mg MAS (Adderall) followed by 10 mg Adderall and placebo 5 mg, 10 mg MPH; placebo; 5 mg, 10 mg MAS (Adderall) 5 mg, 10 mg MAS (Adderall); placebo; 5 mg, 10 mg MPH Placebo; 5 mg, 10 mg MPH; 5 mg, 10 mg MAS (Adderall) 5 mg, 10 mg MAS (Adderall); 5 mg, 10 mg MPH; placebo Mean MPH dosage: LD‐MPH 10 mg/d; HD‐MPH 20 mg/d Administration schedule: morning and midday Duration of each medication condition: 1 week Washout before trial initiation: none Medication‐free period between interventions: none Titration period: none, although 5 mg dose was given before 10 mg, initiated after randomisation Treatment compliance: parents were required to return all unused capsules, but nothing further was said about this
Outcomes	ADHD symptoms Parent‐ and teacher‐rated ADHD/ODD Rating Scales: completed over previous treatment week Non‐serious AEs Barkley Side Effects Rating Scale: completed by adolescent, parent and teacher at the end of each treatment week
Notes	Sample calculation: not described Ethics approval: yes Comments from trial authors Teens are more independent of their parents than are younger children, spending more time outside parental supervision. This raises serious questions about the sensitivity of parental reports to drug and dose response Limitations: most noteworthy was the poor co‐operation of teachers. As a consequence, the statistical power of the trial to detect drug effects on these measures, often the most sensitive to stimulant drug effects, was greatly reduced Key conclusion of trial authors In conclusion, the present trial suggested that both MAS and MPH may have been clinically effective in the management of teens with ADHD when non‐blinded, global clinical judgements of improvement, which were based on multiple sources of information, were used. Even so, these positive drug responses could not be documented at the group level of statistical analysis by using more specific and systematic ratings by parents and teachers. Clinicians undertaking stimulant trials in such contexts need to be aware of the many challenges to the internal validity of these procedures that are likely to occur in drug trials with teens Comment from review authors To exclude participants with low IQ was a post hoc decision Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; excluded patients who had a history of AEs to stimulants Any withdrawals due to AEs: no Funding source: University of Massachusetts Medical School Email correspondence with trial authors: January 2014. We received additional information (see Krogh 2014a [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Email correspondence with trial author: “Randomization was done by me as best as I can recall” (Krogh 2014a [pers comm])
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Opaque gelatin capsules were prepared by the pharmacist
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	High risk	Completer analysis reported 11/46 teens LTFU, 15 parents LTFU, 33 English teachers and 31 Maths teachers LTFU Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Low risk	Email correspondence with trial author: "All planned analyses were done and all measures we collected as treatment endpoints were analyzed" (Krogh 2014a [pers comm])