Safety of medicines used for ADHD in children: A review of published prospective clinical trials

Objective: To assess the long-term safety of drugs for attention deficit hyperactivity disorder (ADHD). Methods: A bibliographic search was performed in the MEDLINE, EMBASE and PsycINFO databases for prospective studies evaluating the incidence of adverse events (AEs) in children and adolescents treated for ADHD. Results: A total of six prospective studies that monitored drug safety during therapy for at least 12 weeks were retrieved. The drugs studied were atomoxetine (two studies, 802 patients), osmotic-controlled released oral methylphenidate formulation (two studies, 512 patients), extended release formulation of mixed amphetamine salts (one study, 568 patients) and transdermal methylphenidate (one study, 326 patients). Heterogeneity was found in the duration of follow-up (ranging between 1 and 4 years) and in the way data were reported. The rate of treatment-related AEs ranged from 58% to 78%, and the rate of discontinuation due to AEs ranged from 8% to 25% of the children. Decreased appetite, insomnia, headache and abdominal pain were the most common AEs observed. Most AEs and cases of discontinuation occurred during the first few months of treatment. Conclusions: Few studies evaluated the long-term safety of drugs for ADHD. Heterogeneity in follow-up duration and in data reporting made comparing different studies and drugs difficult. A systematic monitoring of long-term safety is needed.