A total of 18 randomised controlled trials (RCTs) met the inclusion criteria. However, only 16 RCTs (six parallel and 10 crossover) reported sufficient data to be included in the meta-analyses. The total number of patients was unclear, but sample sizes ranged from 8 to 221. No evidence of publication bias was found.
The main analysis found a significant overall effect size of 0.42 (95% CI 0.20 to 0.63) across all trial designs. Significant heterogeneity was reported. Effect sizes were similar when trials were grouped by design (crossover d=0.44, 95% CI 0.27 to 0.60; parallel d=0.36, 95% CI -0.17 to 0.88), although the crossover trials displayed a significant effect. Substantial heterogeneity was reported within the parallel group trials.
Subgroup analysis according to rater (self versus observer) based on seven trials which reported both self and observer rated outcomes. It was reported that the effect sizes in each subgroup were significantly different from zero, but there were no significant differences between self and observer ratings. Significant heterogeneity was noted on in the observer rating subgroup.
Meta-regression found no significant effect of mean daily dose of methylphenidate on attention-deficit and hyperactivity disorder symptoms. The fail-safe N required to nullify the overall effect was 144 trials. The exclusion sensitivity plot found the overall effect size did not change significantly with exclusion of any single trial; some trials reduced the degree of heterogeneity.
The post-hoc analyses found no significant impact of treatment duration on effect size; there was also no change to the overall results when analysing patients with co-morbid substance abuse.