Overtoom 2003.

Study characteristics
Methods	Double‐blind, randomised, cross‐over trial with 4 interventions: MPH desipramine L‐dopa placebo
Participants	Number of participants screened: not stated Number of participants included: 16 Number of participants followed up: 16 (all boys) Number of withdrawals: 0 Diagnosis of ADHD: DSM‐III‐R (combined (100%)) Age: mean 10.4 years (range 7‐12) IQ: 95.4 MPH‐naive: 0 (0%) Ethnicity: not stated Country: the Netherlands Setting: outpatient clinic Comorbidity: ODD (n = 6), comorbid anxiety disorder (n = 1), specific developmental disorders (n = 3) Comedication: not stated Other sociodemographics: none Inclusion criteria Diagnosis of ADHD according to DSM‐III‐R criteria Scored in the clinical range on both the CBCL Inattention factor (t scores > 70, i.e. 98th percentile) and CTRS Hyperactivity factor (mean factor score > 2.2) Exclusion criteria Diagnosis of tic disorder or pervasive developmental disorder Abnormal values (1 week before medication trial) of ECG and blood measures that contraindicate desipramine medication Family history of severe heart problems
Interventions	Participants were randomly assigned to 1 of 2 of the possible drug condition orders of MPH, desipramine, L‐dopa and placebo Mean MPH dosage: 15 mg Administration schedule: once, in the afternoon Duration of each medication condition: 1 day Washout before trial initiation: 3 days before for MPH users Medication‐free period between interventions: not stated Titration period: none Treatment compliance: 100%
Outcomes	Non‐serious AEs Sleepiness reported by 1 participant
Notes	Sample calculation: no Ethics approval: yes Key conclusions of trial authors Inhibition of performance improved under desipramine but not under MPH or L‐dopa. Response time to the stop signal was marginally shortened after intake of desipramine MPH decreases omission and choice errors and causes faster reaction times in trials without the stop tone No effects of L‐dopa whatsoever were noted Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; all participants were already stable on MPH Any withdrawals due to AEs: no Funding source: Netherlands Organisation for Scientific Research (NWO) Grant 575‐63‐082
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	"A double‐blind randomised design was used"
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): no
Selective reporting (reporting bias)	Unclear risk	No protocol available