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. 2023 Mar 27;2023(3):CD009885. doi: 10.1002/14651858.CD009885.pub3

Fitzpatrick 1992a.

Study characteristics
Methods Cross‐over trial with 4 interventions

  1. ER‐MPH

  2. Standard MPH

  3. Combination

  4. Placebo


Phases: 4 pharmaceutical conditions, each lasting 2 weeks (including weekends), with different dosage schedules based on weight of child and type of intervention
Participants Number of participants screened: not stated
Number of participants included: 19 (17 boys, 2 girls)
Number of participants followed up: not stated
Number of withdrawals: not stated
Diagnosis of ADD: DSM‐III during Diagnostic Instrument for Childhood and Adolescence (ADD with hyperactivity 16/19) (ADD without hyperactivity 3/19)
Age: mean 8.71 years (SD 1.33, range 6.9 to 11.5)
IQ: 114.11 (SD 13.34)
MPH‐naive: 18
Ethnicity: not stated
Country: USA
Setting: outpatient clinic
Comorbidity: oppositional disorder (n = 12), oppositional + CD (n = 1), enuresis (n = 2), encopresis (n = 2), phobia (n = 1), overanxious (n = 1), adjustment disorder (n = 1)
Comedication: not stated
Other sociodemographics: middle class (Hollingshead 4‐factor mean 38.11, SD 13.18)
Inclusion criteria

  1. Not explicitly stated


Exclusion criteria

  1. Not explicitly stated
Interventions Participants were randomly assigned to 1 of 24 (3 MPH and 1 placebo) possible drug condition orders of ER‐MPH (SR), standard MPH (SA), MPH combination and placebo
Mean MPH dosage: SRSA‐MPH 17.1 mg (0.56 mg/kg), SASR‐MPH 20 mg (0.67 mg/kg), combination 11.8 mg SA MPH + 20 mg SR MPH (0.38 mg/kg SA, 0.67 mg/kg SR)
Administration schedule: ER‐MPH, mornings (8:00 am) daily, SA MPH morning (8:00 am) and noon daily
Duration of each medication condition: 2 weeks
Washout before trial initiation: not stated
Medication‐free period between interventions: not stated
Titration period: not stated
Treatment compliance: parents phoned weekly to encourage compliance. School nurse contacted at the beginning of each individual's participation to promote co‐operation and to check on compliance
Outcomes ADHD symptoms

  1. Conners' Hyperactivity Index: parent‐ and teacher‐rated, weekly (although results were averaged over treatment phase)

  2. IOWA Inattention/Overactivity and Aggression/Non‐compliance Scales: parent‐ and teacher‐rated, weekly

  3. Hyperactivity, Attention and Aggression subscales of Loney’s Time on Task Scale (TOTS): every 2 weeks


General behaviour

  1. Selected items of Child Psychiatric Scale: observer, end of each laboratory session (i.e. after 14 days of treatment)


Non‐serious AEs

  1. Interviewed: 12 side effect symptoms: drawn from Subject’s Treatment Emergent Symptom Scale, parents, end of each treatment phase

  2. Body weight: start of each laboratory session
Notes Sample calculation: not stated
Ethics approval: not stated
Key conclusions of trial authors

  1. MPH conditions were superior to placebo and were comparable with one another

  2. Findings suggest comparable effectiveness for ER and standard preparations of MPH

  3. Improved behaviour and improved information processing under stimulant conditions


Comment from review authors

  1. This trial was not actually randomised; therefore we cannot use data on ADHD symptoms and general behaviour ‐ only data on AEs


Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: not clear
Any withdrawals due to AEs: not clear
Funding source: National Institute of Mental Health (NIMH) grant MH38118
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) High risk Double‐blind trial consisting of 4 pharmacological conditions, each lasting 2 weeks and ordered according to a Latin square (i.e. not randomly assigned)
Allocation concealment (selection bias) High risk Not randomised
Blinding of participants and personnel (performance bias)
All outcomes Low risk Double‐blind. Blindness was maintained by administering placebo tablets consisting of the vehicle for the SA and SR preparations, respectively, as appropriate for each condition
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Not stated
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Data for 6 participants on Paired Associate Learning Test excluded, as they could not read well, but this was not 1 of our outcomes
Selection bias (e.g. titration after randomisation): no, but because of emergent side effects, reductions of 2.5 mg SA MPH per dose were performed blindly for 1 participant in the combined condition. Similarly, blinded (but sham) adjustments of SA placebo were made for 2 participants in the placebo phase and for 1 in the SR condition
Selective reporting (reporting bias) Unclear risk No protocol identified