Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents
Evidence Summaries Level of Evidence = B
Amphetamines appear to improve the core symptoms of ADHD in children and adolescents in the short term compared with placebo but are also associated with higher risk of experiencing adverse events.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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