Methylphenidate benefits and harms in children and adolescents with attention deficit/hyperactivity disorder: Two Cochrane systematic reviews

The evidence regarding the benefits and harms of methylphenidate in children and adolescents with ADHD remains inconclusive. Between 2012 and 2018, we conducted two Cochrane systematic reviews on methylphenidate for ADHD. All procedures, such as searches, data extraction and quality assessment followed Cochrane guidelines. The first review included 185 randomised clinical trials. We observed possible beneficial effects of methylphenidate versus placebo or no-intervention, but methodological flaws, such as lack of blinding, outcome reporting bias and heterogeneity, prevented the effective evaluation of the magnitude of intervention effects. The meta-analysis of serious adverse events was considerably underpowered to identify a difference in these events, preventing the drawing of firm conclusions. Methylphenidate increased the risk of non-serious adverse events, with the most common events being appetite suppression and difficulty sleeping. This review has been heavily exposed in many critical articles and editorials. We have rebutted the criticism and have shown that the evidence base for the use of methylphenidate for children and adolescents is indeed flawed. The second review included 260 non-randomised studies, with over 2.2 million participants. Methylphenidate significantly increased the risk of serious adverse events compared to no-intervention. More than 50% of the participants treated with methylphenidate experienced one or more adverse events considered to be non-serious. Our comprehensive reviews of methylphenidate in children and adolescents with ADHD indicate that much of the ADHD research to date is seriously undermined by avoidable methodological flaws that could lead to an overestimation of benefits and an underestimation of harms of methylphenidate