| Study characteristics |
| Methods |
12‐month, parallel RCT with 4 arms
Follow‐up at baseline (before treatment), at end of titration (3‐4 weeks) and after 4, 8 and 12 months of treatment
Follow‐up trial of cohort completing the 12‐month RCT: participants were evaluated annually for 5 years |
| Participants |
Number of participants screened: 302
Number of participants included: 91 included in the RCT (74 boys, 17 girls)
Number of participants followed up: 63 (MPH 45, placebo 18)
Number of withdrawals: 28 (MPH 1, placebo 27)
Diagnosis of ADHD: DSM‐III‐R diagnosis of ADHD (subtype not stated)
Mean age: MPH 8.4 years, placebo 8.3 years (range 6‐12)
IQ: mean (MPH 110.3; placebo 107.6)
MPH‐naive: 100%
Ethnicity: not stated
Country: Canada
Setting: research unit at hospital
Comorbidity: ODD (MPH 56.5%, placebo 44.4%), CD (MPH 6.5%, placebo 20.0%), anxiety (MPH 21.7%, placebo 24.4%)
Comedication: no
Other sociodemographics: placebo group had a higher score at baseline for psychosocial adversity than those assigned to the MPH group
Psychosocial risk index: MPH 1.5%, placebo 2.7%
Inclusion criteria
Screening
Age between 6 and 12 years ≥ 6 of 14 ADHD symptoms on the ADHD‐RS (DuPaul 1991a) Parental report of some ADHD symptoms at school No previous treatment with MPH Willingness to participate in a trial that involved random assignment to treatments for ADHD (both pharmacological and non‐pharmacological) ≥ 1 parent able to communicate in English
Diagnostic evaluation
Exhibit pervasive ADHD, defined as ≥ 8 of the 14 DSM‐III‐R criteria for ADHD, in 1 setting (at home on the PICS, or at school on the Teacher Telephone Interview (prepared by trial authors)) and ≥ 5 ADHD criteria in the other setting History of ADHD symptoms of ≥ 6 months’ duration before the age of 7 years
Final inclusion criteria
Exhibit pervasive ADHD, defined as ≥ 8 of the 14 DSM‐III‐R criteria for ADHD in 1 setting and ≥ 5 ADHD criteria in the other setting History of ADHD symptoms of ≥ 6 months' duration before the age of 7 years Estimated full‐scale IQ > 80 No primary anxiety or affective disorder
Exclusion criteria
Attending a full‐time residential or day treatment programme Has received regular medication for a medical problem Chronic medical condition including a severe motor or vocal tic disorder and Tourette's syndrome Prior treatment for tics
|
| Interventions |
Randomly assigned to 1 of the 4 treatment groups after stratification based on comorbid, conduct or oppositional disorder: MPH + parent training/parent support, placebo + parent training/parent support
Number of participants randomised: MPH 46, placebo 45
Titration period: 3‐4 weeks (depending on child's weight) after randomisation
Mean MPH dosage: target dose 0.7 mg/kg body weight, twice daily
Administration schedule: breakfast and lunch
Duration of intervention: 12 months
Treatment compliance: MPH 80%, placebo 64% |
| Outcomes |
ADHD symptoms
General behaviour
Parent‐ and teacher‐rated telephone interview probe (TIP) ("(Corkum et al., unpublished data available from authors)" Schachar 1997a, p. 756) questionnaire at baseline and at 4 months. Grouped into 4 factors: inattention, hyperactivity‐impulsivity, oppositional behaviour, difficulty experienced by rater in dealing with typical daily problem situations
Non‐serious adverse effects
Parent‐ and teacher‐rated questionnaire with 14 common side effects (modified from Barkley 1990) administered by telephone at baseline, at end of titration and at 4 months. Grouped into 4 factors: affective, overfocusing, physiological and tics. Parent‐rated questionnaire with 16 possible adverse effects (also modified from Barkley 1990) at annual evaluations (telephone interviews) Height and weight were measured at baseline, at week 3‐ 4 and at 4 months in the RCT, and annually in the follow‐up trial. Standing height was measured in cm without shoes from floor to vertex of head. Weight in indoor clothing, without shoes, was measured in kg. Baseline and annual measures of height and weight were ascertained with the same stadiometer Presence and severity of tics were rated at baseline, end of titration, 4 months, 8 months and 12 months by research assistants interviewing parents and teachers. Moderate and severe Tourette's‐like symptoms were assessed and diagnosed by the supervising psychiatrist
|
| Notes |
Sample calculation: yes
Ethics approval: yes
Comments from trial authors
Current RCT is limited by sample size and by medium statistical power This cannot be generalised to situations in which higher doses of MPH may be used, or to children with more than moderate tics Instrument used to measure adverse effects was originally designed for short‐term pharmacological studies and could fail to identify potentially long‐term health concerns in the follow‐up trial Sample in the follow‐up trial of previous participants in an RCT would be biased in favour of adherence relative to a cohort chosen and followed from the time of identification Infrequent contact with participants and lack of an untreated control group are additional limitations of the follow‐up trial Study did not include pubertal staging
Key conclusions of trial authors
RCT
Positive effects of MPH on behaviour are evident in the classroom, but with MPH given twice daily, parents did not report that MPH improved behaviour at home Comorbid anxiety did not appear to influence development of side effects or behavioural response to MPH when dose was titrated as in standard clinical practice Doses of MPH based on the typical clinical titration procedure did not produce significantly more tics than placebo in children with or without pre‐existing (mild to moderate) tics
Follow‐up trial
Psychostimulants improve ADHD symptoms for up to 5 years, but adverse effects persist Long‐term use of high doses of stimulants during a period of 1‐5 years is likely to have measurable effects on rate of growth in school‐aged children with attention deficit hyperactivity disorder
Comments from review authors
Data in both Schachar 1997a and Diamond 1999 (secondary reference under Schachar 1997a) are preliminary (interim results of first 4 months of treatment). Data from the 2 placebo groups (cointervention: parent training and parent support) and the 2 MPH groups (same 2 cointerventions) are combined (placebo vs MPH). No final report focuses on ADHD symptoms As participants are allowed to switch from the allocated intervention group during the trial, we can use only data regarding adverse effects
Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no
Any withdrawals due to AEs: yes. “Side effects were the stated reason for discontinuing MPH in five cases”
Funding source: Medical Research Council of Canada, National Health Research Development Program of Canada and the Department of Psychiatry, The Hospital for Sick Children, Toronto. Placebo pills were provided by Ciba Geigy, Canada, Ltd
Email correspondence with trial authors: September‐October 2013. Unfortunately, they were not able to provide supplemental data |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Randomly assigned after stratification based on the presence of comorbid conduct or oppositional disorder and assigned to 1 of the 4 treatment groups. Randomly assigned based on a random number table |
| Allocation concealment (selection bias) |
Low risk |
Concealed from the physician and participants before randomisation and maintained throughout the trial |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
All participants (child, research staff, parents and teachers) were blinded to the medication assignment |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
All participants (child, research staff, parents and teachers) were blinded to the medication assignment |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
No imputation method: the effect of treatment was analysed among participants who adhered to their original medication assignment. At the 4‐month point, children not taking any medication were grouped with those taking placebo. When a participant switched from placebo to MPH treatment, they were counted within the MPH group
Selection bias (e.g. titration after randomisation → exclusion): no |
| Selective reporting (reporting bias) |
Unclear risk |
Not possible to find protocol |
