Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy

Objective: To synthesise existing knowledge of the efficacy and safety of long-acting versus short-acting methylphenidate for paediatric attention deficit hyperactivity disorder (ADHD). Design: Systematic review and meta-analysis. Data sources: Electronic literature search of CENTRAL, MEDLINE, PreMEDLINE, CINAHL, EMBASE, PsychINFO, Scopus and Web of Science for articles published in the English language between 1950 and 2012. Reference lists of included studies were checked for additional studies. Study selection: Randomised controlled trials of paediatric ADHD patients (<18 years), comparing a long-acting methylphenidate form to a short-acting methylphenidate form. Data extraction: Two authors independently selected trials, extracted data and assessed risk of bias. Continuous outcomes were compared using standardised mean differences (SMDs) between treatment groups. Adverse events were compared using risk differences between treatment groups. Heterogeneity was explored by subgroup analysis based on the type of long-acting formulation used. Results: Thirteen RCTs were included; data from 882 participants contributed to the analysis. Meta-analysis of three studies which used parent ratings to report on hyperactivity/impulsivity had an SMD of -0.30 (95% CI -0.51 to -0.08) favouring the long-acting forms. In contrast, three studies used teacher ratings to report on hyperactivity and had an SMD of 0.29 (95% CI 0.05 to 0.52) favouring the short-acting methylphenidate. In addition, subgroup analysis of three studies which used parent ratings to report on inattention/overactivity indicate that the osmotic release oral system generation long-acting formulation was favoured with an SMD of -0.35 (95% CI -0.52 to -0.17), while the second generation showed less efficacy than the short-acting formulation with an SMD of 0.42 (95% CI 0.17 to 0.68). The long-acting formulations presented with slightly more total reported adverse events (n=578) as compared with the short-acting formulation (n=566). Conclusions: The findings from this systematic review indicate that the long-acting forms have a modest effect on the severity of inattention/overactivity and hyperactivity/impulsivity according to parent reports, whereas the short-acting methylphenidate was preferred according to teacher reports for hyperactivity.