Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)

Background Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015. Objectives To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. Search methods We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate. Selection criteria We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non‐serious, general behaviour, and quality of life. Data collection and analysis Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel‐group trials and first‐period data from cross‐over trials formed the basis of our primary analyses. We undertook separate analyses using end‐of‐last period data from cross‐over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach. Main results We included 212 trials (16,302 participants randomised); 55 parallel‐group trials (8104 participants randomised), and 156 cross‐over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross‐over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male‐female rat