Sixty-five RCTs were included in the review, of which four were included in industry submissions and no details were included in the report. The total number of participants in the included studies was not reported.
The majority of studies scored poorly on the validity assessment: only five studies adequately reported the method of randomisation, nine reported that the sequence of allocation was truly random, and while most were blinded none reported whether blinding was successful.
MPH: most studies reported that medium-dose MPH was superior to placebo for hyperactivity; the results for low-dose and high-dose MPH were variable. There was a paucity of studies comparing MPH plus a non-drug intervention with placebo, or comparing MPH with a non-drug intervention. Combined treatment with MPH plus a non-drug intervention was generally superior to non-drug treatment alone for hyperactivity (three studies) and Clinical Global Impression (CGI; two studies). Two poor-quality studies that compared IR-MPH and ER-MPH reported no differences for hyperactivity or CGI.
DEX: only two studies that compared DEX and placebo reported reproducible data on hyperactivity. The efficacy of medium-dose DEX varied with the scale used, while hyperactivity and CGI appeared to be improved by higher dose DEX. One study compared DEX or sustained-release DEX (DEX-SR) in combination with a non-drug treatment against non-drug treatment alone. For IR DEX, the results for hyperactivity varied with the scale used. For DEX-SR, combination treatment resulted in improved behaviour compared with non-drug treatment alone. However, this study scored poorly on the quality assessment.
ATX: there was consistent evidence from a number of studies (including two good-quality studies) that ATX was superior to placebo for hyperactivity and CGI. No studies compared ATX with non-drug treatments.
Other comparisons: the results of comparisons between MPH and DEX were variable. One poorly reported study found no difference between MPH and ATX for hyperactivity or CGI.
MPH: studies comparing low-dose MPH with placebo found no differences in adverse events. Medium- and high-dose MPH was associated with increased incidence of headache, loss of appetite, stomach ache and insomnia. ER-MPH was associated with decreased appetite and increased insomnia compared with placebo. One study reported a significantly increased incidence of headache with ER-MPH compared with IR-MPH.
DEX: one study of medium-dose DEX reported no difference in adverse events compared with placebo. A study of high-dose DEX found a greater incidence of loss of appetite in the DEX group. In another study, significantly decreased appetite and increased insomnia were reported in patients receiving DEX plus non-drug treatment compared with those receiving non-drug treatment alone.
ATX: ATX at all doses was associated with significantly reduced appetite compared with placebo, but did not affect the incidence of headache, stomach ache or insomnia. One trial reported that ATX appeared to have an adverse effect on children's weight gain.
Other comparisons: one study found an increased incidence of reduced appetite and insomnia in patients treated with ER-MPH compared with those treated with ATX (low or medium dose). Other drug comparisons found no significant differences for adverse events.