No Long-term Impact of ADHD Meds on the Brain

Emma Hitt, PhD

July 25, 2012

July 25, 2012 — Attention-deficit/hyperactivity disorder (ADHD) medications may have no long-term effects, at least with respect to dopamine, on the brain, according to the findings of a new study conducted in primates.

"These findings add to our understanding of their potential long-term effects," lead researcher Linda J. Porrino, PhD, from Wake Forest School of Medicine in Winston-Salem, North Carolina, told Medscape Medical News.

"Although we know that there do not appear to be any untoward behavioral effects in children, there had been no measurements of brain development in children," Dr. Porrino added.

"Our studies fill this gap and show that the extended-release form of methylphenidate, the form most often used in children, did not result in any lingering negative influences on brain development."

The study is published in the July issue of Neuropsychopharmacology.

Dr. Porrino and colleagues studied 16 juvenile nonhuman primates whose ages were equivalent to that 6- to 10-year-old humans. Eight animals served as control subjects and received no drug, while 8 received a dose of extended-release methylphenidate for a period of 1 year.

Brain structure before and after treatment was measured with positron emission tomography (PET) scan; developmental growth was also measured. The animals were then allowed to self-administer cocaine for a period of several months.

Animals treated with methylphenidate appeared to be no more inclined toward substance abuse than those who served as control subjects, the researchers found.

According to Dr. Porrino, a sister study was conducted simultaneously at Johns Hopkins University with slightly older animals and different drugs, and their findings were similar.

"We feel very confident of the results because we have replicated each other's studies within the same time frame and gotten similar results," she said in a written release. "We think that's pretty powerful and reassuring."

"Practically, these data provide reassurances to both physicians and parents that the drugs will not produce long-lasting harm," Dr. Porrino said. "This is particularly important with respect to questions about vulnerability for later substance abuse."

According to Dr. Porrino, remaining questions include whether there are sex differences and whether age at the start of treatment makes any difference with respect to outcomes.

In an independent comment, Shankar Sadasivan, PhD, with St. Jude Children's Research Hospital in Memphis, Tennessee, noted that the findings of this study are of interest to the medical community, especially because of a dearth of long-term studies in the literature regarding the use of methylphenidate.

"This study allays fears of drug reinforcement issues surrounding chronic methylphenidate use among adolescents later on in their life," he told Medscape Medical News.

However, he added that although the authors did not find a change in D2/D3 receptors using PET, they may not be able determine the much finer effects of methylphenidate administration.

"There is evidence in the literature that methylphenidate exposure causes changes at the molecular level in different regions of the brain which may not be evidenced by PET imaging," he said.

According to Dr. Sadasivan, the major shortcoming of this study, one that has been acknowledged in the article, is that "these experiments were conducted in 'normal' nonhuman primates, and it would have been interesting to see if the effects were consistent in an experimental model of ADHD."

"Also, this paper does not address effects of methylphenidate on other neurotransmitter systems such as norepinephrine or serotonin," he added. "Hence, one must interpret the results with caution about the safety of the long-term consequences of the drug in the brain," he said.

The research was not commercially funded. Richard J. Smeyne, PhD, also with St. Jude Children's Hospital, cosigned the comments received by email from Dr. Sadasivan. The authors and independent commentators have disclosed no relevant financial relationships.

Neuropsychopharmacology. Published online July 18, 2012. Abstract

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