Experts Urge Caution When Prescribing Common ADHD Drug in Kids

Megan Brooks

November 26, 2015

A comprehensive Cochrane Review shows there is very low-quality evidence to support the use of methylphenidate (Ritalin, Concerta, other brands) in children with attention deficit hyperactivity disorder (ADHD) leading the reviewers to urge more caution when prescribing the stimulant.

"The evidence is not as convincing as many clinicians have believed regarding the benefits of methylphenidate," lead authors Ole Jakob Storebø, PhD, clinical psychologist, Region Zealand, Roskilde, Denmark, and Morris Zwi, MBBCh, consultant child and adolescent psychiatrist, Whittington Health, London, UK, told Medscape Medical News.

"In general, our findings raise concerns about how much we should expect of this medicine, and there needs to be more caution when prescribing methylphenidate. I think it probably calls for a change of mindset more than a change in practice," the investigators note.

The review was published online November 25 in the Cochrane Database of Systematic Reviews.

Perceptions Out of Step With the Evidence

The review includes published data through February 2015 from 185 randomized controlled trials involving more than 12,000 children and adolescents aged 3 to 18 (mean age, 9.7). The studies, conducted mainly in the United States, Canada, and Europe, compared methylphenidate with placebo or no intervention. The duration of methylphenidate treatment ranged from 1 to 425 days, with an average duration of 75 days.

Seventy-two (40%) of the studies were funded by industry. All 185 trials were assessed to be at high risk of bias, the reviewers said.

Their analysis found that methylphenidate may improve teacher-rated ADHD symptoms (standardized mean difference [SMD] -0.77; 95% confidence interval [CI] -0.90 to -0.64), which corresponds to a mean difference (MD) of -9.6 points (95% CI -13.75 to -6.38) on the ADHD Rating Scale (ADHD-RS).

A change of 6.6 points on the ADHD-RS is considered clinically to represent the minimal relevant difference, the reviewers note.

The data also suggest improvement with methylphenidate on teacher-rated general behavior (SMD -0.87; 95% CI -1.04 to -0.71) and parent-reported quality of life (SMD 0.61; 95% CI 0.42 - 0.80) on the Child Health Questionnaire.

Methylphenidate was not associated with an increase in serious life-threatening adverse events (risk ratio [RR] 0.98; 95% CI 0.44 - 2.22), but there was an increased risk of nonserious adverse events (RR 1.29; 95% CI 1.06 - 1.56), most commonly sleep problems and decreased appetite. Children taking methylphenidate had a 60% greater risk for trouble sleeping/sleep problems (RR 1.60; 95% CI 1.15 - 2.23) and 266% greater risk for decreased appetite (RR 3.66; 95% CI 2.56 - 5.23).

The reviewers caution, however, that the "low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects." And "very little" is known about the long-term effects or harms, as most of the trials in the review did not measure outcomes beyond 6 months.

"Our confidence in the analysis results is very low," Dr Storebø and Dr Zwi told Medscape Medical News. "Although the effect of methylphenidate on ADHD symptoms, general behavior, and quality of life in children (up to and including 18 years of age) is favorable, the studies included in our review had a number of methodological weaknesses."

"We should view the average reduction in symptom scores attributable to treatment with a high degree of caution," they add. "Clinicians need to weigh what we now believe to be an uncertain degree of benefit against the many adverse events that are known to be associated with methylphenidate, such as appetite suppression and sleep difficulties. The general perception of methylphenidate as an effective drug for all children with ADHD seems out of step with the new evidence. This new information from our review should challenge the mindset of clinicians because there is more uncertainty to factor in to balancing the benefits and risks of this medication," the investigators noted.

On the other hand, they said, "clinicians need to be mindful of the consequences of stopping methylphenidate in those children whose ADHD symptoms are lower, have improved general behavior, and improved quality of life, as long as they do not also suffer from the adverse effects of medication."

Overall, this review "highlights the need for long-term, better-designed trials that recruit sufficient numbers of participants for us to be more certain about the benefits and harms of methylphenidate treatment (compared with placebo) in children and adolescents with ADHD,” the researchers conclude.

The investigators note that their research team "is preparing a companion systematic review that will look specifically at evidence from nonrandomized studies. We hope that this will provide better insights into the long-term risk of adverse events from taking methylphenidate."

Biggest Weakness

Commenting on the review for Medscape Medical News, Bonnie J Kaplan, PhD, of the Child Development Centre, University of Calgary, Alberta, Canada, said congratulations to the team are in order for "recognizing that one of the important weaknesses in the studies they examined were 'the short follow-up periods typical of the included trials.'"

"This is a very, very important limitation," Dr Kaplan said, "because children who show benefit in an acute situation are often kept on this medication for years and years. And the latest long-term data from the MTA [Multimodal Treatment Study of Children With ADHD] trial suggests that the benefits are negligible in the long run."

Cochrane Database Syst Rev. Published online November 25, 2015. Abstract

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