A Cochrane review [Abstract] 3 included 38 parallel-group (n=5 111) and 147 cross-over trials (n=7 134) involving both sexes, at a boys-to-girls ratio of 5:1, aged 3 to 18 years (the average age was 9.7 years). The average duration of methylphenidate treatment was 75 days. Methylphenidate was compared to placebo (175 trials) or no intervention (10 trials). It improved teacher-rated ADHD symptoms (SMD -0.77, 95% CI -0.90 to -0.64; 19 trials, n=1698) corresponding to a MD of -9.6 points (95% CI -13.75 to -6.38) on the ADHD Rating Scale (a change of 6.6 points is considered clinically to be a minimally relevant difference). There was no evidence of serious adverse events (RR 0.98, 95% CI 0.44 to 2.22; 9 trials, n=1532).Teacher-rated general behaviour improved with methylphenidate (SMD -0.87, 95% CI -1.04 to -0.71; 5 trials, n=668).The change on the Child Health Questionnaire was 8.0 points (95% CI 5.49 to 10.46; 3 trials; 7 points is a minimal clinically relevant difference) suggesting that methylphenidate may improve parent-reported quality of life (SMD 0.61, 95% CI 0.42 to 0.80; 3 trials, n=514). Children in the methylphenidate group were at 60% greater risk for sleep problems (RR 1.60, 95% CI 1.15 to 2.23; 13 trials, n=2416), and 266% greater risk for decreased appetite (RR 3.66, 95% CI 2.56 to 5.23; 16 trials, n=2962) than those in the control group.
A systematic review 2 including 22 RCTs with 2203 patients was abstracted in DARE. The patients were adults with any subtype of ADHD. The drugs studied were amphetamine mixture, dextroamphetamine sulphate, methylphenidate, dexmethylphenidate, modafinil, atomoxetine and bupropion. All treatments were significantly more likely to produce a clinical response than placebo. For shorter-acting stimulants, such as methylphenidate, the RR was 4.32 (95% CI 3.03 to 6.16). For longer-acting forms of bupropion it was 1.87 (95% CI 1.36 to 2.58), for longer-acting stimulants it was 1.35 (95% CI 0.997 to 1.84). Indirect comparisons showed significant differences between the drug classes (Χ2 = 24.15, p = 0.0001), with shorter-acting stimulants being superior to longer-acting forms of bupropion (p = 0.008) and longer-acting stimulants (p < 0.001). All drug types had similar risks of early treatment discontinuation. There was limited and conflicting evidence of comparability of drug types in incidence of appetite loss and sleep disturbance, but all showed higher incidence than placebo.
A Cochrane review [Abstract] 3 included 6 studies with a total of 438 adults. All studies evaluated a long-acting version of bupropion, the intervention varied from 6 to 10 weeks. Bupropion decreased the severity of ADHD symptoms (SMD -0.50, 95% CI -0.86 to -0.15; 3 studies, n=129), and increased the proportion of participants achieving clinical improvement (RR 1.50, 95% CI 1.13 to 1.99; 4 studies, n=315), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50; 5 studies, n=337). The proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10; 3 studies, n=253).
Comment:The quality of evidence is downgraded by study quality (inadequate allocation concealment, high number of patients excluded from analyses, and incomplete outcome data) and indirectness (short follow-up time).
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