In two recent Cochrane reviews «Storebø OJ, Ramstad E, Krogh HB ym. Methylphenidat...»1, «Punja S, Shamseer L, Hartling L ym. Amphetamines f...»2 efficacy and safety of methylphenidate (MPH) and amphetamines (dexamphetamine, lisdexamphetamine and mixed amphetamine salts), short- and long-acting formulations were compared with placebo in the treatment of ADHD in children and adolescents.
In a Cochrane review of methylphenidate in November 2015 «Storebø OJ, Ramstad E, Krogh HB ym. Methylphenidat...»1 185 trials (from 449 reports) were included in MPH studies with 38 parallel-group trials (N = 5 111 participants randomized) and 147 cross-over trials (7 134 participants randomized), boys-to-girls ratio was 5:1, and participants' ages ranged from 3 to 18 years (mean age 9.7 years). The duration of methylphenidate treatment ranged from 1 to 425 days, mean 75 days, three were long-term trials (≥ six months).
Among those prescribed methylphenidate, 526 per 1 000 (range 448 to 615) experienced non-serious adverse events compared with 408 per 1 000 in the control group. This equates to a 29 % increase in the overall risk of any non-serious adverse events (RR 1.29, CI 95 % 1.10 to 1.51; 21 trials, 3 132 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 1.29 (CI 95 % 1.06 to 1.56). The most common non-serious adverse events were sleep problems and decreased appetite. Children in the methylphenidate group were at 60 % greater risk for trouble sleeping/sleep problems (RR 1.60, CI 95 % 1.15 to 2.23; 13 trials, 2 416 participants), and 266 % greater risk for decreased appetite (RR 3.66, CI 95 % 2.56 to 5.23; 16 trials, 2 962 participants) than children in the control group. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio (RR) 0,98, CI 95 % 0.44 to 2.22; 9 trials, 1 532 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 0.91 (CI 95 % 0.02 to 33.2).
The Cochrane review of amphetamines «Punja S, Shamseer L, Hartling L ym. Amphetamines f...»2was publish in February 2016. 23 trials (8 parallel-group and 15 cross-over trials), with 2 675 children aged three years to 17 years compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months.
In the amphetamine studies the most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; CI 95 % 2.58 to 15.46; 11 studies; 2 467 children/adolescents), insomnia (RR 3.80; CI 95 % 2.12 to 6.83; 10 studies; 2 429 children/adolescents), and abdominal pain (RR 1.44; CI 95 % 1.03 to 2.00; 10 studies; 2 155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; CI 95 % 1.18 to 1.44; 6 studies; 1 742 children/adolescents; low quality evidence). There was no difference between the amphetamine and placebo groups in the proportion of children and adolescents who withdrew due to an adverse event (RR 1.60; CI 95 % 0.86 to 2.98; Tau² = 0.00; I² = 0%; 9 studies; 2 160 children/adolescents).