ADHD News & Research

Even After Stopping ADHD Medications, Children’s Brains Show Differences

Children who are treated with methylphenidate continue to show increased blood flow in their brains even after the medication is gone from their systems, new research says — but the long-term consequences of these changes remain unknown.

August 10, 2016

Even after stimulants are washed out of their systems, children’s brains still show residual changes in blood flow and dopamine levels, a new study finds — suggesting a phenomenon called “neurochemical imprinting” whose long-term consequences, at least when it comes to ADHD medications, are uncertain.

The study, which was published August 3 in JAMA Psychiatry, looked at 99 male patients falling in the age ranges of either 10 to 12 or 23 to 40. Fifty of the patients were treated with methylphenidate for 16 weeks, while the other 49 were treated for the same period with a placebo. During the four-month treatment span, researchers used pharmacologic MRIs to gauge blood flow in the cerebrum — a criterion for assessing dopamine stimulation in the brain — and continued measuring until one week after the medication had been stopped.

The children who were treated with methylphenidate showed a significant increase in cerebral blood flow when they started the medication — an increase that maintained itself even after treatment ended and the medication was fully washed out of their bodies. The placebo groups saw no similar effects, and the adults who were treated with methylphenidate returned to their baseline levels of cerebral blood flow almost immediately once the 16-week medication period was over.

This phenomenon — known as neurochemical imprinting — isn’t new, in and of itself. Other drugs have created similar results in animal brains; the changes in blood flow remain in developing brains even after the medication has been stopped, but fully developed brains return to baseline levels as soon as the medication has washed out of the body.

But researchers were intrigued by the results of this study, for a number of reasons: for one, it was the first such study on ADHD medication in human children and adults, and for another, it’s uncertain at this point what the long-term effects are. “We do not know if these lasting alterations persist for weeks, months or even years,” said Liesbeth Reneman, M.D., Ph.D., the study’s lead author. “Thus, the clinical implications of methylphenidate altering the developing DA-ergic system [the dopamine pathways in the brain] are still unclear.”

The results are already begging for follow-up studies, the researchers write. ADHD medications, while historically viewed as safe, have disappointingly little research tracking their long-term effects. The changes in blood flow seen in this study may be one piece of that puzzle — perhaps a particularly critical one, as it gives us hints to how stimulant medications prescribed in childhood affect patients’ brain development as they grow into adults.

The researchers don’t want to draw too many conclusions, at this early stage. But, since the long-term effects of these brain changes are currently unknown, Reneman hypothesizes that there may be a need for stricter regulation of methylphenidate prescriptions. “Our results call for a tighter regulation of ADHD diagnoses and more careful patient selection, as an increasing number of children are being treated with methylphenidate,” she said.