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

Abstract

Study queStionIs methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? MethodSElectronic 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 liMitationSThe 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 addSThe 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.

Does methylphenidate improve academic performance? A systematic review and meta-analysis

“…Results from our meta-regression suggest that ER formulations are equally effective as IR formulations in improving academic performance, which is in line with findings from individual studies comparing ER and IR formulations [52,62,63]. We found no effects of titration method (clinical titration prior to the trial or fixed dosages) which is also in line with findings from [61]. Possibly, to optimize the effects of MPH on academic outcome, titration should be based on academic outcomes instead of on symptom improvements.…”

“…Demographic and disorder-related variables included in our analysis (age, gender, ADHD subtype and ADHD severity) did not moderate MPH efficacy on math performance either. The absence of a moderating effect of age and comorbid disorders is in line with the results of a recent meta-analysis on behavioral improvements with MPH [61]. In the meta-analysis by Storebø and colleagues, some evidence was found for a moderating effect of ADHD subtype and behavioral improvements, with highest MPH efficacy for the inattentive subtype.…”

“…The absence of an effect of dose on academic performance is in line with the findings from Prasad et al [13], who found no difference between studies comparing the effect of 0.3 mg/kg or 10 mg fixed dose to 0.6 mg/kg or 17.5-20 mg fixed dose on percentage seatwork completed. Also in line with this are the results from [61], who found no effects of dose on symptom improvements.…”

Non-diagnostic based approaches to helping children who could be labelled ADHD and their families

“…Reviews of pharmacotherapy studies note the inadequate reporting of drug trial methodology, publication bias, limited reliability of results, inadequate data regarding adverse events, and lack of evidence of long term benefit (e.g. Storebø et al, 2015). The most commonly cited reference in support of using stimulant medication is the American multi-modal treatment of ADHD (MTA) study, which concluded, in a 14-month randomized controlled trial, that patients receiving medication had better outcomes compared to those who did not (MTA Cooperative Group, 1999).…”

Aufmerksamkeitsdefizit‑/Hyperaktivitätsstörung

“…B. eine Sonderschule), können Medikamente indiziert sein (Psychostimulanzien und Atomoxetin, weitere Informationen in den Leitlinien [18,29]). Die Wirksamkeit von ADHS-Medikamenten ist wissenschaftlich belegt (SMD 0,61-0,87 [26]), allerdings werden die Qualität und der methodische Standard der Studien als gering bewertet, und es fehlen methodisch verlässliche Langzeituntersuchungen [26]. Voraussetzungen für eine medikamentöse Therapie sind ausreichende ärztliche Erfahrung, regelmäßige Verlaufskontrollen und eine Weiterführung der bereits eingeleiteten, nichtmedikamentösen Maßnahmen.…”