Young people on amphetamines for ADHD have twice psychosis risk compared to other stimulants, study says

Posted at 10:49 AM, Mar 21, 2019

Teens and young adults with attention deficit-hyperactivity disorder, ADHD, who receive amphetamines such as Adderall for treatment have a higher risk of developing psychosis, compared to those who receive methyphenidates stimulants, such as Ritalin, according to a large new study.

Using two national insurance claim databases, the authors followed 221,486 teens and young adults ages 13 to 25 with ADHD who were prescribed a stimulant for the first time between the years 2004 and 2015. Half received amphetamines such as Adderall and half received methylphenidates such as Ritalin.

A total of 343 of the teens and young adults who were followed — or one out of every 660 young people — developed an episode of psychosis in the few months after starting on a stimulant. The risk for this rare but serious side effect was twice as high — 0.21% — for those taking amphetamine, compared to 0.1% for those taking methylphenidate, according to the results published Wednesday in the New England Journal of Medicine.

“We’ve seen cases of people coming in without much of a psychiatric history who are developing this sort of first episode of psychosis in the setting of stimulant use, most commonly Adderall,” said Dr. Lauren Moran, assistant professor at Harvard Medical School, practicing psychiatrist at McLean Hospital, and lead author of the study. Moran said her observations caring for young people experiencing psychosis prompted the research.

ADHD is a developmental disorder, and its symptoms include inattention, hyperactivity, and restlessness or impulsivity that is more severe, frequent or debilitating than normal. Stimulants have been shown to be effective in controlling these symptoms. Since 2007 the US Food and Drug Administration has required manufacturers to add a warning to drug labels, stating “stimulants may cause treatment-emergent psychotic or manic symptoms in patients with no prior history.”

Current guidelines recommend either methylphenidate or amphetamine as first line treatment of ADHD when a medication is required. Teens and young adults were four times more likely to receive a prescription for amphetamine such as Adderall in 2015 compared to 2004, and 1.6 times more likely to receive one for methylphenidates such as Ritalin, according to the new research.

“There are subtle differences in the way Adderall and Ritalin affect dopamine systems in the brain,” Moran said. Both stimulants work through dopamine pathways in the brain, but Adderall is more likely to cause a release of dopamine, whereas Ritalin is more likely to block the re-uptake, allowing it to linger. The surge of dopamine during a psychotic episode most closely mimics that seen after stimulant use like Adderall, which may explain some of the findings, Moran added.

Dr. Rebecca Baum, a developmental and behavioral pediatrician at Nationwide Children’s Hospital in Ohio who was not involved in the study, says she worries the results may alarm parents and scare them away from effective treatments for their children.

“Any time we use a medication we are certainly thinking about what is the benefit of the medication versus the risk,” said Baum, stressing that ADHD can be a debilitating condition when symptoms aren’t well-controlled, and while psychosis is a real and potentially serious side effect, it is still very rare.

“The vast majority of my patients have ADHD and I have the benefit of being able to treat many patients quite successfully,” said Baum. “Thankfully in my practice it is not a side effect that we see very often,” she added.

Moran also adds that she and her team focused the study on teens and young adults who were taking stimulants for the first time, emphasizing that for those who have been on these medications and have been taking them as prescribed, the risk is likely even lower.

As for parents and young adults weighing whether to start a medication, Moran hopes the research will prompt a conversation about risks, benefits and alternatives such as behavioral therapy and non-stimulants.