Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

Study queStion Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? MethodS Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour. Study anSwer and liMitationS The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) −0.77, n=1698), corresponding to a mean difference of −9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD −0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE. what thiS Study addS The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events. Funding, CoMpeting intereStS, data Sharing Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library. Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated childhood psychiatric disorders,1 with a prevalence of 3.4%.2 It is increasingly seen as a developmental disorder, which has high comorbidity with other psychiatric disorders.3 Diagnosis is made through recognition of excessive inattention, hyperactivity, and impulsivity in children before 12 years of age, which impairs their functioning or development.4 5 Methylphenidate has been used for the treatment of ADHD for over 50 years and is now globally the most common drug treatment for the disorder.6 7 Despite the WhAT IS AlReAdy knoWn on ThIS TopIC Methylphenidate has been used for the treatment of attention-deficit/hyperactivity disorder for over 50 years and is globally the most common treatment for the disorder Despite the widespread use of methylphenidate, no comprehensive systematic reviews of benefits and harms have been done WhAT ThIS STudy AddS The results of meta-analyses suggest that methylphenidate may improve teacher reported ADHD symptoms, teacher reported general behaviour, and parent reported quality of life among children and adolescents with a diagnosis of ADHD The low quality of the underpinning evidence means that the magnitude of the effects is uncertain Within the short follow-up periods typical of the included trials, there is some evidence that methylphenidate is associated with increased risk of non-serious adverse events, such as sleep problems and decreased appetite, but no evidence that it increases the risk of serious adverse events