Twenty-three RCTs were included. Some studies were cross-over studies. Several studies evaluated more than one active stimulant drug. Amphetamine versus placebo was evaluated in 405 patients who received amphetamine and 482 who received placebo. Methylphenidate versus placebo was evaluated in 1,603 patients who received methylphenidate and 1,253 who received placebo.
The authors calculated 99 study-level standardised mean differences (total ADHD symptoms 73 effect sizes, inattention subscale nine effect sizes and hyperactivity-impulsivity 17 effect sizes).
Standardised mean differences were greater for: children compared with adolescents (SMD 0.89 versus 0.64, p<0.001); and teacher-rated (SMD 0.92) and physician-rated (SMD 0.96) versus parent-rated (SMD 0.73) and self-rated (SMD 0.47) scores (0.47, p<0.001); and outcome scores versus change scores (SMD 0.93 versus 0.75, p=0.03). After controlling for these potential confounders, standardised mean differences for amphetamine studies were significantly greater than SMDs for methylphenidate studies (p=0.008). No other variables examined showed any significant influence.
There was evidence of significant publication bias for studies of methylphenidate (p=0.03), but not for amphetamine studies. After adjusting standardised mean differences using the trim and fill method, standardised mean differences for amphetamine studies remained significantly greater than for methylphenidate studies (SMD 0.99 versus 0.72, p=0.01)
Standardised mean differences for amphetamine studies were significantly greater than standardised mean differences for methylphenidate studies for all ADHD symptoms (SMD 1.03 versus 0.77, p=0.02 and NNT 2.0, 95% CI 1.7 to 2.2 for amphetamine versus 2.6, 95% CI 2.4 to 2.8 for methylphenidate) and for hyperactivity-impulsivity symptoms (SMD 1.20 versus 0.91, p=0.01). Only one amphetamine study evaluated inattentive symptoms. There was substantial heterogeneity for ADHD total scores for both amphetamine (I2=74.5%) and methylphenidate (I2=45.4%) and hyperactivity-impulsivity scores for methylphenidate (I2=68.5%).