Adderall high doses linked to greater psychosis or mania risk, study finds

Adderall is an effective treatment for attention deficit hyperactivity disorder (ADHD), yet the steep increase in United States prescriptions during the past two decades has raised researchers’ concerns about uncommon but severe side effects.

A notable study published on Thursday, led by psychiatrist Lauren Moran at Mass General Brigham in Boston, found that people prescribed high doses of the stimulant have more than a fivefold greater risk of developing psychosis or mania.

Important issues include the absence of maximum-dose guidance and the marked growth in use of the drug among young adults since the Covid-19 pandemic, largely associated with the expansion of telemedicine providers.

Moran told AFP that her interest in the issue began while working on a hospital inpatient ward treating university students in the Greater Boston area.

"We were just seeing a lot of people coming in without much of a psychiatric history, developing the first episode of psychosis or mania in the context of using prescription stimulants," she said.

Adderall study findings and psychosis risk

After the Food and Drug Administration learned of such cases in the 2000s, it added a warning to the medicine’s label. However, little research had been carried out to measure the frequency of the side effects or establish how they were connected to dosage.

For the study, Moran and her team examined electronic medical records for people aged 16 to 35 who were admitted to Mass General Brigham hospitals between 2005 and 2019. These are the ages at which psychosis, or a loss of contact with reality, commonly begins.

The team identified 1,374 people undergoing a first episode of psychosis or mania - a disruptive condition marked by high energy and erratic behaviour - and compared them with 2,748 control patients admitted for other psychiatric disorders.

By reviewing Adderall use in the preceding month and accounting for variables including substance use, the researchers could isolate the effects of stimulants.

They found that people who had taken Adderall were 2.68 times more likely to have been admitted to hospital with psychosis or mania than those who had not taken it. At higher doses of 40 milligrams and above, the likelihood rose to 5.28 times.

A separate analysis found no elevated risk for Ritalin, another stimulant used to treat ADHD. Moran suggested that this may reflect important differences in the way the two medicines function.

How Adderall and Ritalin affect dopamine

Both drugs increase levels of dopamine, a chemical messenger involved in the brain’s reward system, motivation and learning. Adderall, an amphetamine, raises dopamine release, whereas Ritalin works by preventing dopamine from being reabsorbed.

Telemedicine companies and Adderall prescribing

Moran said a key finding was the need for explicit maximum dose limits on drug labels. Although the existing label recommends treating patients with 20 milligrams, prescribing practices differ considerably between doctors.

This variation is partly explained by severe ADHD symptoms that can require higher doses. However, Moran has sometimes seen "carelessness in dose prescribing," while in other cases patients may "shop" for a doctor prepared to prescribe what they seek.

"People, including clinicians, might think they can eliminate all ADHD symptoms, but that's not a realistic expectation," she added.

Telemedicine companies in particular have faced scrutiny over allegations that they prescribe Adderall too readily, worsening shortages for people who genuinely require the drug.

The Drug Enforcement Administration had proposed ending telehealth prescriptions for Adderall, but extended them until the end of 2024 following substantial public feedback.

© Agence France-Presse