MedicalResearch.com Interview with:
Dr. Ole Jakob Storebø
Region Zealand, Child and Adolescent Psychiatric Department, Roskilde
Region Zealand Psychiatry
Psychiatric Research Unit, Slagelse
University of Southern Denmark
Department of Psychology
Faculty of Health Science,
Medical Research: What is the background for this study? What are the main findings?
Dr. Storebø: Despite widespread use of methylphenidate for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD), a comprehensive systematic review of its benefits and harms has not yet been conducted. Over the past 15 years, several reviews investigating the efficacy of methylphenidate for ADHD (with or without meta-analyses) have been published. Each of these reviews, however, has several shortcomings and these are described in detail in the review. The most important concerns are that none of these reviews are based on a pre-published protocol, and most assessed neither the risk of bias (systematic errors) of included trials nor adverse events. Moreover, none of these reviews considered the risk of random errors. Therefore, their interpretation of findings is unlikely to have taken into account the poor reporting of adverse events, the impact of combining data from small trial samples, or the impact of risk of bias on their analyses; information about adverse events is also missing from several RCTs. Because of this it is our opinion that these previous reviews might have overestimated the true treatment effect.
We found that Methylphenidate may improve ADHD symptoms, general behaviour and quality of life in children and adolescents aged 18 years and younger with ADHD. We rated the evidence to be of very low quality and, as a result, we cannot be certain about the magnitude of the effects from the meta-analyses. The evidence is limited by serious risk of bias in the included trials, under-reporting of relevant outcome data, and a high level of statistical variation between the results. We found no evidence for serious adverse events, but a lot of non-serious adverse events. Most of these are well known but the number of adverse events might even be higher than the number we found due to underreporting of adverse events. We know very little about the long term effects or harms as most of the trials in our review did not measure outcomes beyond 6 months. The risk of rare, serious adverse events seem low over the short duration of follow-up of the trials that reported on harms, but in general there was inadequate reporting of adverse events in many trials.
Medical Research: What should clinicians and patients take away from your report?
Dr. Storebø: Clinicians should not have high expectations of methylphenidate, but on the other hand they should not be too quick to stop using it, as noted.
ADHD is a complex condition and we still need research to understand it and to identify effective treatment strategies. There might be many other ways to investigate supporting young people with ADHD. For example, research could explore whether more support within school settings is warranted or teaching them in a way that takes into consideration their difficulties in maintaining focused attention. If methylphenidate treatment is considered, clinicians should remember that the information we do have relates to its short-term effects. Careful monitoring of both benefits and harms in children medicated in this way will be important. If there is little or no apparent benefit through reduced ADHD symptoms in children taking a well-monitored, carefully titrated dose, consideration should be given to discontinuing it, especially if harmful side effects are present.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Storebø: To assess whether any benefits are provided by methylphenidate, large, randomised clinical trials must be conducted. In addition, such trials ought to be designed according to the SPIRIT (Standard Protocol Items: Recommendations for Intervention Trials) guidelines and reported in keeping with CONSORT (Consolidated Standards of Reporting Trials).
Future trials ought to publish depersonalised individual participant data and should report all outcomes, including adverse events, to ensure that future systematic reviews and meta-analyses can access and use individual participant data. Only through meta-analyses will we be able to assess differences between intervention effects according to gender, age, type of ADHD, presence of co-morbidities and dose.
Our team of researchers is preparing a companion systematic review that will look specifically at evidence from non-randomised studies. We hope that this will provide better insights in to the long-term risk of adverse events from taking methyphenidate.
Storebø OJ, Ramstad E, Krogh HB, Nilausen TD, Skoog M, Holmskov M, Rosendal S, Groth C, Magnusson FL, Moreira-Maia CR, Gillies D, Buch Rasmussen K, Gauci D, Zwi M, Kirubakaran R, Forsbøl B, Simonsen E, Gluud C. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No.: CD009885. DOI: 10.1002/14651858.CD009885.pub2.
Dr. Ole Jakob Storebø (2015). Cochrane Analysis Reviews Studies of Ritalin For ADHD MedicalResearch.com