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White-Matter Changes Linked to Methylphenidate Treatment in Boys With ADHD

August 15, 2019

By Anne Harding

NEW YORK—Boys with attention-deficit/hyperactivity disorder (ADHD) show changes in brain white matter (WM) after four months of treatment with methylphenidate (MPH), according to a new randomized controlled trial.

Treatment did not affect white matter in young adult males with ADHD, nor were there changes in boys or men who received a placebo, Dr. Liesbeth Reneman of the University of Amsterdam and colleagues found.

"The ADHD medication methylphenidate lastingly affects white matter development of boys with ADHD, and . . . this probably is because the brain is plastic (still developing)," Dr. Reneman told Reuters Health by email.

ADHD itself has been linked to changes in WM development in both children and adults, she and her colleagues note in Radiology, online August 13. In their own research, they have found increases in fractional anisotropy (FA) in adolescent rats given MPH, but not in adults.

Dr. Reneman and her team randomly assigned 50 boys and 48 young men with ADHD to receive MPH or placebo for four months. Using diffusion-tensor imaging and voxel-based analysis, they found significant effects of time-by-medication-by-age in white matter tracts in the boys given MPH.

Several association tracts in the left hemisphere and the lateral aspect of the truncus of the corpus callosum had a greater increase in FA (standardized effect size, 5.25).

It's not clear if the WM changes would have a positive or negative effect, Dr. Reneman said, because the study did not include boys without ADHD.

"Our study highlights the importance for further research on this topic in children and adolescents treated with methylphenidate, as our findings are only relevant for boys of a certain age (10-12 years) with ADHD," the researcher, adding that "girls differ considerably in brain white-matter development (and so) we do not know if our findings are applicable to them as well."

"Also we do not know if they are applicable to other ADHD medications than methylphenidate, and whether these effects are reversible or not, and related to functional or behavioural changes over a longer period of time," she said. "We still need to establish the long-term implications of our findings, which we are currently doing with a 4-year follow up study."

"We do not think that doctors should stop prescribing (methylphenidate) to children," Dr. Reneman said. "We think our data further underscore the importance that ADHD medications should only be prescribed to children who actually have ADHD and are significantly affected by it."

Francisco X. Castellanos, a professor of child and adolescent psychiatry at NYU Langone Health in New York City, called the study "impressive, credible and intriguing," although he questioned the analysis used to arrive at the "astonishing standardized effect size of 5.25 standard deviations (SD)."

"I mainly offer my congratulations to the authors and caution that we do not know enough about how to interpret FA or similar metrics yet to be able to interpret these and forthcoming results in terms of their clinical implications," he told Reuters Health by email.


Radiology 2019.

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