Brown 1991.

Study characteristics
Methods	Double‐blind, randomised, cross‐over trial with 2 interventions: MPH placebo Phases: MPH 10 mg MPH 15 mg MPH 20 mg placebo
Participants	Trial consisted of 22 participants, but only 7 had ADD. As outcomes were reported separately for these 7 participants, we were able to include the trial Number of participants screened: 25 Number of participants included: 7/22 (all boys) Number of participants followed up: 22 Number of withdrawals: 0 Diagnosis: DSM‐III (CD, with 7 of 22 also diagnosed with ADD) Age: mean:15.8 years (range 12.9‐18.9) IQ: 96.22 (SD 15.12, range 80‐123) MPH‐naive: not stated Ethnicity: white (100%) Country: USA Setting: hospital Comorbidity: CD (100%) Comedication: occasional allergy medication was allowed Other sociodemographics: middle and upper‐middle class Inclusion criteria Hospitalised adolescents diagnosed with CD Exclusion criteria Mental disability, psychosis and organic brain disorder
Interventions	Participants were randomly assigned to 1 of 24 possible drug condition orders of MPH (10 mg, 15 mg, 20 mg) and placebo (in counterbalanced order) Mean MPH dosage: 0.15 mg/kg, 0.22 mg/kg and 0.31 mg/kg Administration schedule: twice daily, 8:00 am and 12:00 pm Duration of each medication condition: 1 day each, 3 days of MPH in all Washout before trial initiation: not stated Titration period: 1 day before first phase to test tolerability Treatment compliance: 100%
Outcomes	General behaviour CTRS (conduct factor): teacher‐rated daily Non‐serious AEs Side Effects Rating Scale (including 17 known AEs for MPH): observer‐rated daily Cardiovascular measures were recorded 90 min after 12:00 pm administration
Notes	Sample calculation: not stated Ethics approval: not stated Comments from trial authors "... in our trial, mean milligram per kilogram doses were lower than in previously published reports … doses may simply have been too small to induce any real change in behaviour" "Another limitation that may have influenced the results is timing of the measurements of behaviour. As behavioural ratings were made by teachers at the end of the day, it is possible that medication effects (particularly for lower doses) had dissipated by the time the ratings were made" Key conclusions of trial authors "In summary, results are of theoretical importance and with additional research may suggest the potential efficacy of stimulants for treating adolescents with CDs in the absence of ADD" "The present data may be interpreted to suggest that ADD may be managed with stimulant medication when it presents comorbidly with CD" Comment from review authors Data on the CD + ADD group were reported separately in the trial ‐ that is why we could use the data Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; initially participants received a 1‐day open trial of MPH. 3 participants were excluded because of intolerability Any withdrawals due to AEs: no Funding source: not stated Email correspondence with trial authors: unable to locate contact details for trial authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	All participants received each of the 4 doses in 1 of 24 possible randomly assigned sequences
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	MPH and placebo were packaged in coloured gelatin capsules by the hospital pharmacist to avoid detection of dose, visually or by taste
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Under double‐blinded conditions
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants followed up Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol published