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Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)

Overview of attention for article published in Cochrane database of systematic reviews, November 2015
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  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#19 of 8,886)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

news
30 news outlets
blogs
13 blogs
twitter
391 tweeters
peer_reviews
1 peer review site
facebook
33 Facebook pages
wikipedia
3 Wikipedia pages
googleplus
5 Google+ users

Citations

dimensions_citation
117 Dimensions

Readers on

mendeley
465 Mendeley
citeulike
3 CiteULike
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Title
Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
Published in
Cochrane database of systematic reviews, November 2015
DOI 10.1002/14651858.cd009885.pub2
Pubmed ID
Authors

Ole Jakob Storebø, Erica Ramstad, Helle B. Krogh, Trine Danvad Nilausen, Maria Skoog, Mathilde Holmskov, Susanne Rosendal, Camilla Groth, Frederik L Magnusson, Carlos R Moreira-Maia, Donna Gillies, Kirsten Buch Rasmussen, Dorothy Gauci, Morris Zwi, Richard Kirubakaran, Bente Forsbøl, Erik Simonsen, Christian Gluud

Abstract

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children with ADHD find it difficult to pay attention, they are hyperactive and impulsive.Methylphenidate is the drug most often prescribed to treat children and adolescents with ADHD but, despite its widespread use, this is the first comprehensive systematic review of its benefits and harms. To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. In February 2015 we searched six databases (CENTRAL, Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, Conference Proceedings Citations Index), and two trials registers. We checked for additional trials in the reference lists of relevant reviews and included trials. We contacted the pharmaceutical companies that manufacture methylphenidate to request published and unpublished data. We included all randomised controlled trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. At least 75% of participants needed to have an intellectual quotient of at least 70 (i.e. normal intellectual functioning). Outcomes assessed included ADHD symptoms, serious adverse events, non-serious adverse events, general behaviour and quality of life. Seventeen review authors participated in data extraction and risk of bias assessment, and two review authors independently performed all tasks. We used standard methodological procedures expected within Cochrane. Data from parallel-group trials and first period data from cross-over trials formed the basis of our primary analyses; separate analyses were undertaken using post-cross-over data from cross-over trials. We used Trial Sequential Analyses to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for high risk of bias, imprecision, indirectness, heterogeneity and publication bias. The studies.We included 38 parallel-group trials (5111 participants randomised) and 147 cross-over trials (7134 participants randomised). Participants included individuals of both sexes, at a boys-to-girls ratio of 5:1, and participants' ages ranged from 3 to 18 years across most studies (in two studies ages ranged from 3 to 21 years). The average age across all studies was 9.7 years. Most participants were from high-income countries.The duration of methylphenidate treatment ranged from 1 to 425 days, with an average duration of 75 days. Methylphenidate was compared to placebo (175 trials) or no intervention (10 trials). Risk of Bias.All 185 trials were assessed to be at high risk of bias. Primary outcomes. Methylphenidate may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -0.90 to -0.64; 19 trials, 1698 participants; very low-quality evidence). This corresponds to a mean difference (MD) of -9.6 points (95% CI -13.75 to -6.38) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points; DuPaul 1991a). A change of 6.6 points on the ADHD-RS is considered clinically to represent the minimal relevant difference. There was no evidence that methylphenidate was associated with an increase in serious (e.g. life threatening) adverse events (risk ratio (RR) 0.98, 95% CI 0.44 to 2.22; 9 trials, 1532 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 0.91 (CI 0.02 to 33.2). Among those prescribed methylphenidate, 526 per 1000 (range 448 to 615) experienced non-serious adverse events, compared with 408 per 1000 in the control group. This equates to a 29% increase in the overall risk of any non-serious adverse events (RR 1.29, 95% CI 1.10 to 1.51; 21 trials, 3132 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 1.29 (CI 1.06 to 1.56). The most common non-serious adverse events were sleep problems and decreased appetite. Children in the methylphenidate group were at 60% greater risk for trouble sleeping/sleep problems (RR 1.60, 95% CI 1.15 to 2.23; 13 trials, 2416 participants), and 266% greater risk for decreased appetite (RR 3.66, 95% CI 2.56 to 5.23; 16 trials, 2962 participants) than children in the control group.Teacher-rated general behaviour seemed to improve with methylphenidate (SMD -0.87, 95% CI -1.04 to -0.71; 5 trials, 668 participants; very low-quality evidence).A change of seven points on the Child Health Questionnaire (CHQ; range 0 to 100 points; Landgraf 1998) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a MD of 8.0 points (95% CI 5.49 to 10.46) on the CHQ, which suggests that methylphenidate may improve parent-reported quality of life (SMD 0.61, 95% CI 0.42 to 0.80; 3 trials, 514 participants; very low-quality evidence). 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 diagnosed with ADHD. However, the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects. 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 risk of serious adverse events.Better designed trials are needed to assess the benefits of methylphenidate. Given the frequency of non-serious adverse events associated with methylphenidate, the particular difficulties for blinding of participants and outcome assessors point to the advantage of large, 'nocebo tablet' controlled trials. These use a placebo-like substance that causes adverse events in the control arm that are comparable to those associated with methylphenidate. However, for ethical reasons, such trials should first be conducted with adults, who can give their informed consent.Future trials should publish depersonalised individual participant data and report all outcomes, including adverse events. This will enable researchers conducting systematic reviews to assess differences between intervention effects according to age, sex, comorbidity, type of ADHD and dose. Finally, the findings highlight the urgent need for large RCTs of non-pharmacological treatments.

Twitter Demographics

The data shown below were collected from the profiles of 391 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 465 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 <1%
Spain 1 <1%
Chile 1 <1%
France 1 <1%
South Africa 1 <1%
Switzerland 1 <1%
Denmark 1 <1%
Taiwan 1 <1%
Japan 1 <1%
Other 3 <1%
Unknown 451 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 84 18%
Researcher 74 16%
Student > Bachelor 60 13%
Unspecified 54 12%
Student > Ph. D. Student 53 11%
Other 139 30%
Unknown 1 <1%
Readers by discipline Count As %
Medicine and Dentistry 181 39%
Psychology 76 16%
Unspecified 75 16%
Nursing and Health Professions 34 7%
Social Sciences 20 4%
Other 78 17%
Unknown 1 <1%

Attention Score in Context

This research output has an Altmetric Attention Score of 573. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 February 2019.
All research outputs
#10,602
of 12,518,850 outputs
Outputs from Cochrane database of systematic reviews
#19
of 8,886 outputs
Outputs of similar age
#316
of 343,994 outputs
Outputs of similar age from Cochrane database of systematic reviews
#1
of 197 outputs
Altmetric has tracked 12,518,850 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,886 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.1. This one has done particularly well, scoring higher than 99% of its peers.
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We're also able to compare this research output to 197 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.