Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents - Assessment of Adverse Events in Nonrandomised Studies

Summary

A Cochrane review [Abstract] 1 included 260 studies. Seven of them were comparative cohort studies, 6 (n=1134) compared methylphenidate to controls, and one (n=1224) assessed patients who were exposed or not exposed to methylphenidate during different time periods; 4 patient-control studies (n=73 098); 177 non-comparative cohort studies (n=2 207 751); 2 cross-sectional studies (n=96) and 70 patient reports/series (n=206). Patients' ages ranged from 3 years to 20 years.

Primary outcomes: In the comparative studies, methylphenidate increased the RR of serious adverse events (RR 1.36, 95% CI 1.17 to 1.57; 2 studies, n=72 005); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, n=71 771); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, n=1224) compared to no intervention. In the non-comparative cohort studies, the proportion of patients on methylphenidate experiencing any serious adverse event was 1.20% (95% CI 0.70% to 2.00%; 50 studies, n=162 422). Withdrawal from methylphenidate due to any serious adverse events occurred in 1.20% (95% CI 0.60% to 2.30%; 7 studies, n= 1173) and adverse events of unknown severity led to withdrawal in 7.30% of patients (95% CI 5.30% to 10.0%; 22 studies, n=3708).

Secondary outcomes: In the comparative studies, methylphenidate, compared to no intervention, increased the RR of insomnia and sleep problems (RR 2.58, 95% CI 1.24 to 5.34; 3 studies, n=425) and decreased appetite (RR 15.06, 95% CI 2.12 to 106.83; 1 study, n=335). With non-comparative cohort studies, the proportion of participants on methylphenidate with any non-serious adverse events was 51.2% (95% CI 41.2% to 61.1%; 49 studies, n=13 978). These included difficulty falling asleep, 17.9% (95% CI 14.7% to 21.6%; 82 studies, n=11 507); headache, 14.4% (95% CI 11.3% to 18.3%; 90 studies, n=13 469); abdominal pain, 10.7% (95% CI 8.60% to 13.3%; 79 studies, n=11 750); and decreased appetite, 31.1% (95% CI 26.5% to 36.2%; 84 studies, n= 11 594). Withdrawal of methylphenidate due to non-serious adverse events occurred in 6.20% (95% CI 4.80% to 7.90%; 37 studies, n=7142), and 16.2% were withdrawn for unknown reasons (95% CI 13.0% to 19.9%; 57 studies, n=8340).