The quality of evidence is downgraded by inconsistency (unexplained variability in results).
A Cochrane review 1 included 23 studies with a total of 2,675 children aged 3 to 17 years comparing amphetamines to placebo. Twelve studies assessed mixed amphetamine salts, 7 used dextroamphetamine and 6 studies looked at lisdexamphetamine; 2 studies assessed two amphetamine derivatives. Study durations ranged from 14 days to 365 days, with the majority lasting less than 6 months. Amphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57, 95% CI -0.86 to -0.27; statistical heterogeneity I2=77%; 7 studies, n=1,247), teacher ratings (SMD -0.55, 95% CI -0.83 to -0.27; 5 studies, n=745), and clinician ratings (SMD -0.84, 95% CI -1.32 to -0.36; statistical heterogeneity I2=88%; 3 studies, n=813). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36, 95% CI 2.48 to 4.55; statistical heterogeneity I2=72%; 9 studies, n=2,207).
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, 95% CI 2.58 to 15.46; statistical heterogeneity I2=85%; 11 studies, n=24 67), insomnia (RR 3.80, 95% CI 2.12 to 6.83; statistical heterogeneity I2=59% 10 studies, n=2,429), and abdominal pain (RR 1.44, 95% CI 1.03 to 2.00; 10 studies, n=2,155). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30, 95% CI 1.18 to 1.44; 6 studies, n=1,742).
1. Punja S, Shamseer L, Hartling L et al. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev 2016;(2):CD009996. [PMID:26844979]
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