|Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy
|Punja S, Zorzela L, Hartling L, Urichuk L, Vohra S
This review concluded that long-acting methylphenidate had a modest benefit, over short-acting methylphenidate, for attention or overactivity, and hyperactivity or impulsivity, reported by parents, but short-acting methylphenidate was better, for hyperactivity reported by teachers. Discrepancies in ratings, possible overestimated effect sizes, small samples, and no long-term data, mean that these conclusions may not be reliable.
To assess the efficacy and safety of short-acting versus long-acting methylphenidate, to manage the core symptoms of paediatric attention deficit hyperactivity disorder (ADHD).
MEDLINE, Pre-MEDLINE, CINAHL, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published in English, from 1950 to August 2012. Search terms were reported. Reference lists of included studies were scanned to identify more studies.
Randomised controlled trials (RCTs) that compared long-acting methylphenidate with short-acting methylphenidate, in patients younger than 18 years, with a clinical diagnosis of ADHD, were eligible for inclusion. Trials had to report either efficacy or adverse events. Efficacy was defined as improvement in the core symptoms of ADHD (inattention, impulsivity, and hyperactivity), measured by rating scales, completed by the parent, teacher or both.
The included trials were conducted in the USA, Australia, Germany, Canada or Taiwan. The average age of the participants ranged from 8 to 11 years. Four trials used first-generation and five used second-generation long-acting methylphenidate, and four trials assessed osmotic release oral system (OROS) methylphenidate. Where reported, the intervention lasted from one day to 56 days. Most of the trials had a crossover design. Various rating scales were used.
Two reviewers independently identified trials from searches. Any discrepancies or disagreements were resolved by discussion.
Assessment of study quality
Two reviewers assessed the methodological quality of the trials, using the Cochrane Risk of Bias tool, for sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other bias. Disagreements were resolved through discussion.
Data were extracted to calculate mean changes from baseline and their 95% confidence intervals. Two reviewers independently extracted these data; discrepancies were resolved through discussion. Trial authors were contacted for missing data, if necessary.
Methods of synthesis
Pooled standardised mean differences, and their 95% confidence intervals, were calculated using a random-effects model. Heterogeneity was assessed using Ι². A value of 25% was considered low, 50% was moderate, and 75% was high. Where heterogeneity was detected, a subgroup analysis was performed, based on the type of long-acting methylphenidate. A sensitivity analysis was planned, for only those trials rated as low risk in all six domains of the risk of bias tool.
Results of the review
Thirteen trials, with 1,031 patients (range 13 to 272), were included in the review; eight were included in the meta-analysis. Most trials had an unclear risk of bias for sequence generation and allocation concealment; a low risk of bias for blinding and addressing incomplete outcome data; and a high risk of bias for other domains, due to industry funding.
The meta-analysis showed no significant differences between the short- and long-acting methylphenidate, for inattention or overactivity, and inattention alone reported by teachers and parents; hyperactivity reported by parents; and hyperactivity or impulsivity reported by teachers.
There was a significant reduction in the symptoms of hyperactivity reported by teachers, with short-acting methylphenidate (SMD 0.29, 95% CI 0.05 to 0.52; Ι²=0; 278 patients), and reduced symptoms of hyperactivity or impulsivity reported by parents, with long-acting methylphenidate (SMD -0.31, 95% CI -0.51 to -0.08; Ι²=0; 337 patients). The most commonly reported adverse events were anorexia, headaches, abdominal pain and insomnia, with both long- and short-acting methylphenidate.
The subgroup and sensitivity analysis results were reported.
Long-acting methylphenidate had a modest benefit, over short-acting methylphenidate, for inattention or overactivity, and hyperactivity or impulsivity reported by parents, but short-acting methylphenidate was better, for hyperactivity reported by teachers.
The review question and inclusion criteria were clear. Relevant sources were searched, but not for unpublished trials and trials not in English, which means that some relevant evidence could have been missed. Attempts were made to minimise reviewer error and bias. Trial quality was assessed, using appropriate criteria, but the full results were not presented and it was unclear who was blind to allocation. A reasonable description of individual trials was provided.
Appropriate methods were used to pool the data and assess heterogeneity. Statistically significant differences between long-acting and short-acting forms were observed, for some outcomes, but the clinical significance was unclear. The authors noted that there were discrepancies between parents' and teachers' ratings; a possible overestimation of the treatment effects due to the risk of bias, especially in industry-funded trials; small samples; and a lack of data on the long-term effects.
The authors' conclusions reflect the evidence presented, but these limitations mean that the conclusions may not be reliable. The authors stated that neither the long- nor the short-acting methylphenidate alleviated all the core symptoms of ADHD, across both home and school environments, which seems appropriate.
Implications of the review for practice and research
Practice: The authors stated that discrepancies between parent and teacher ratings could reflect different demands in home and school environments, so the environment in which a child’s ADHD symptoms most affects them, could help guide treatment decisions.
Research: The authors stated that further research was needed to investigate the long-term costs, benefits, and harms of long- and short-acting methylphenidate, for ADHD patients of all subtypes.
No specific funding received.
Punja S, Zorzela L, Hartling L, Urichuk L, Vohra S. Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy. BMJ Open 2013; 3(3): e002312
Subject indexing assigned by CRD
Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Humans; Methylphenidate
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.