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Methylphenidate affects dopaminergic system in children, not adults

Recent findings indicated treatment with methylphenidate for attention-deficit/hyperactivity disorder significantly affected the dopaminergic system in children but not adults.

“Safety investigations on the effects of methylphenidate on [extracellular dopamine] function in the developing brain are scarce in children. Regardless of this alarming paucity of findings, increasingly greater numbers of children and young adolescents are exposed to methylphenidate, many of whom likely do not meet the criteria for ADHD. This heightened use has led to considerable debate and concern (eg, among parents) about the long-term consequences or possible adverse effects of methylphenidate use in children,” Anouk Schrantee, MSc, of University of Amsterdam, and colleagues wrote. “Such knowledge is urgently needed, as recently emphasized by several entities, including the FDA, NIH and the European Committee for Medicinal Products for Human Use.”

To determine age-dependent effects of methylphenidate on the dopaminergic system, researchers conducted a randomized, double-blind, placebo-controlled trial among 50 stimulant treatment-naïve boys, aged 10 to 12 years, and 49 stimulant treatment-naïve men, aged 23 to 40 years diagnosed with ADHD. Study participants received methylphenidate or placebo for 16 weeks.

Methylphenidate increased cerebral blood flow treatment response in the thalamus among children but not adults, with a mean difference of 6.5 (95% CI, 0.4-12.6; P = .04).

Striatal cerebral blood flow was significantly higher among children who received methylphenidate, compared with placebo (mean difference = 7.7; 95% CI, 0.7-14.8; P = .03). This effect was not observed among adults.

“In line with extensive preclinical data, we provide the first evidence, to our knowledge, that methylphenidate treatment during a specific period of maturation alters the [cerebral blood flow] response, likely reflecting increased [extracellular dopamine] neurotransmission due to neurochemical imprinting by methylphenidate. In the short term, these alterations do not induce major benefits or harm regarding clinical improvement, but the long-term consequences remain to be established. Therefore, our data stress the need for longer follow-up studies that address possibly progressive disturbances of the [extracellular dopaminergic] system and associated behavioral abnormalities,” the researchers concluded. – by Amanda Oldt

Disclosure: Schrantee reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.