Study warns: High doses of ADHD medication can cause serious side effects

Adderall is an effective treatment for attention deficit/hyperactivity disorder (ADHD), but a sharp increase in prescriptions in the United States over the past two decades has raised concerns among researchers about rare but serious side effects.

In a remarkable new study published Thursday, a team led by psychiatrist Lauren Moran of Mass General Brigham in Boston found that people taking high doses of the stimulant were more than five times more likely to develop psychosis or mania.

The main factors include the lack of guidelines on maximum dosages and the significant increase in the number of young adults using the drug since the Covid-19 pandemic, largely due to the rise of telemedicine providers.

Moran told AFP her interest grew during her time in a hospital ward in the Boston area where she treated college students.

“We have seen many people who came to us with no significant psychiatric history and whose first psychotic or manic episode occurred in connection with the use of prescription stimulants,” she said.

When the FDA became aware of such cases in the 2000s, it added a warning to the drug's label. However, until then, relatively little research had been done to quantify the frequency of side effects or determine how they related to dosage.

For their study, Moran and colleagues reviewed the electronic health records of people ages 16 to 35 who were admitted to Mass General Brigham hospitals between 2005 and 2019. This is the typical age of onset for psychosis, or loss of touch with reality.

The researchers identified 1,374 people who were experiencing their first episode of psychosis or mania – a disturbed state characterized by high energy and erratic behavior – and compared them with 2,748 control patients hospitalized for other psychiatric illnesses.

By analyzing Adderall use over the previous month and taking into account other variables such as substance use, they were able to determine the effects of stimulants in particular.

They found that the odds of being hospitalized for psychosis or mania were 2.68 times higher among those who had taken Adderall than among those who had not taken Adderall. At higher doses of 40 milligrams and above, that odds increased to 5.28 times.

A separate analysis found no increased risk with Ritalin, another stimulant prescribed for ADHD. Moran suspects this may be due to key differences in how the two drugs work.

Telemedicine companies

Both drugs increase levels of dopamine, a chemical messenger involved in the brain's reward system, motivation and learning. While Adderall, an amphetamine, increases dopamine release, Ritalin works by blocking its reuptake.

For Moran, a key finding was the need for clear maximum dosage limits on the labels. The current label recommends treating patients with 20 milligrams, but in practice, doctors' prescriptions vary widely.

This variability is partly due to the severe impairment of ADHD symptoms, which require higher doses. However, Moran has occasionally observed “carelessness in prescribing dosage,” while in other cases patients “go out and find a doctor” to prescribe them the drug they want.

“People, including clinicians, may think they can eliminate all ADHD symptoms, but that is not a realistic expectation,” she added.

Telemedicine companies in particular are under scrutiny for allegedly overprescribing Adderall, thereby contributing to shortages among patients who really need the drug.

The Drug Enforcement Administration had proposed revoking telemedicine prescriptions for Adderall, but extended them until the end of 2024 in response to significant feedback from the public.

© Agence France-Presse