Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials [盐酸哌甲酯对儿童及青少年注意缺陷/多动障碍的作用]

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BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h5203 (Published 25 November 2015)
Cite this as: BMJ 2015;351:h5203

Authors
Ole Jakob Storebø, senior researcher, Helle B Krogh, medical student, Erica Ramstad, medical student, Carlos R Moreira-Maia, psychiatrist, Mathilde Holmskov, medical student, Maria Skoog, research fellow, Trine Danvad Nilausen, physician, Frederik L Magnusson, medical student, Morris Zwi, child and adolescent psychiatrist and clinical director, Donna Gillies, senior researcher, Susanne Rosendal, psychiatrist, Camilla Groth, PhD student, Kirsten Buch Rasmussen, librarian, Dorothy Gauci, physician, Richard Kirubakaran, physician, Bente Forsbøl, child and adolescent psychiatrist, Erik Simonsen, professor and head of department, Christian Gluud, head of department

Abstract
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.