Nine placebo-controlled RCTs (691 children) were included.
The methodological flaws included: losses to follow-up; failure to analyse by intention-to-treat; inadequate means of dealing with confounding factors; unrepresentative samples; lack of comparison of side-effects between the active treatment and placebo groups; and the use of multiple significance testing.
Short-term studies (8 RCTs, 760 children).
All of the studies were good-quality double-blind crossover studies that included an assessment of inter-observer reliability where this was appropriate. In all studies, the use of methylphenidate was evaluated after 1 to 4 weeks on the drug. All 5 RCTs that assessed individual features of attention, impulsivity and hyperactivity showed significant benefit for methylphenidate compared with placebo. All 6 RCTs that assessed academic effects showed significant benefit for methylphenidate compared with placebo. One study excluded children with co-morbid conduct disorder. Both RCTs, conducted by the same researcher, which assessed the effects of the mother-child relationship showed significant benefit for methylphenidate in comparison with placebo.
Medium-term studies (3 RCTs with end points between 16 weeks and 6 months were identified, but only 1 RCT met all the inclusion criteria).
All 3 RCTs showed significant positive effects of methylphenidate, compared with placebo, on teacher ratings of behaviour and the three cardinal features of hyperkinetic disorder (p<0.01 to p<0.005). The one RCT that met the inclusion criteria assessed the outcomes at 6 months and showed a significant effect of methylphenidate on learning ability, but not memory.
No well-designed long-term studies were identified. The one identified RCT had a drop-out rate of 59% making interpretation problematical. One retrospective cohort study, one prospective cohort study and one unplanned prospective cohort study were found.
Adverse effects (6 RCTs).
Five RCTs (only 3 appear to have met the inclusion criteria) compared the incidence of side-effects in the treatment and control groups. The 2 excluded studies reported adverse events in greater detail and found that the most common side-effects were decreased appetite, insomnia, stomachache and headache. These reactions occurred at higher rates in the methylphenidate-treated groups than in the placebo groups. The rates were 15 to 37% higher for low-dose and 10 to 40% higher for high-dose methylphenidate. These 2 RCTs reported a significant decrease in weight, but not in height, at 4 months and one year. These 2 RCTs were longer term and they reported evidence of growth suppression.