High doses of Adderall linked to this rare mental health risk: What to know.

Hospitalized patients who took high doses of ADHD prescription amphetamines were five times likelier to develop psychosis and mania than patients not on the medication, a study found.

The study of more than 1,300 patients at Mass General Brigham hospitals linked their risk for psychosis and mania to the dosage of prescription stimulants a person took. These medications are used to help people concentrate at school or work. Patients who took 30 milligrams or more of dextroamphetamine − or 40 milligrams of Adderall − developed psychosis and mania nearly 5.3 times more often than those who did not take the medication, according to the study published Thursday in the American Journal of Psychiatry.

The study found no such link for another common ADHD medication methylphenidate, which is sold under the brand name Ritalin.

Past research has shown that psychosis and mania occurred in less than 1% of people who took these commonly used prescription amphetamines. But for the first time, the Mass General Brigham study shows a link between prescription strength and certain rare side effects.

Although the side effects of the drug are a rarity, the study's lead author Lauren Moran said doctors who prescribe these stimulants for attention-deficit/hyperactivity disorder should "maybe stay away from (higher) doses, or just make sure that you're carefully monitoring patients."

Other researchers not involved in the study said it provides important information to doctors who prescribe stimulants such as Adderall.

Nina Kraguljac, a professor of psychiatry and behavioral health at Ohio State University, said the study clarifies that only higher doses of Adderall and other prescription amphetamines are linked to higher risk.

Kraguljac said the study shows doctors may not want to exceed 30 milligrams when prescribing dextroamphetamine or 40 milligrams for Adderall.

"That is absolutely novel, very clinically relevant and very helpful because it also assures you don't necessarily increase your psychosis risk by taking lower to medium doses," said Kraguljac.

Higher doses pose a greater risk

Researchers conducted the study because doctors had noticed some patients with psychosis and mania also had taken prescription amphetamines, said Moran, a psychiatrist and a pharmacoepidemiology researcher at McLean Hospital, a psychiatric hospital in Belmont, Massachusetts.

Moran wanted to investigate the possible link between stimulant use and certain mental health conditions.

Moran's research team gathered medical records of patients admitted to McLean from 2005 through 2019 after first visiting emergency rooms at other Mass General Brigham hospitals in the Boston region. The patients were all between the ages of 16 and 35.

Researchers examined the records of 1,374 patients hospitalized for psychosis or mania and 2,748 patients hospitalized for depression, anxiety or other reasons. People who had been prescribed an amphetamine within the previous month were more likely to be diagnosed with psychosis or mania than those who did not take the medication. Those who took the strongest doses had the greatest odds of developing psychosis or mania. Hospital workers contacted the patients' pharmacies to document which prescription medications and doses they had been given at the time of their hospitalization.

The study evaluated three types of prescription amphetamines: mixed prescription amphetamines, such as Adderall and Mydayis, dextroamphetamine and lisdexamfetamine, which is sold under the brand Vyvanse. Most patients who were prescribed amphetamines were on Adderall, Moran said.

Which ADHD drugs are not linked to psychosis or mania?

Researchers also examined the records of patients who took the ADHD medication methylphenidate and found no increased odds of psychosis or mania. This drug is sold under the brand names Ritalin and Concerta.

Even for people taking Adderall or other prescription amphetamines, the risk is rare. Past research showed psychosis and mania occurred in less than 1% of the patients taking prescription amphetamines. However, Moran said her study suggests doctors should be careful when prescribing high dosages of prescription amphetamines.

Moran said her research team is conducting a national study of patients who were prescribed stimulants to treat ADHD. The study will follow participants who are prescribed low, medium and high doses of ADHD medication. The study will compare rates of psychosis among those taking varying doses of the medication.

Amid shortages, risks of switching ADHD medications

Kraguljac, of Ohio State University, said Adderall is generally a "first-line treatment" for patients with ADHD. Some doctors choose to prescribe Ritalin when patients get side effects from taking Adderall.

However, a nationwide shortage of ADHD drugs in the past two years has prompted some doctors to switch their patients' medications. The shortage has forced patients to search for alternatives or pay for more expensive brand-name drugs. The Drug Enforcement Administration this month announced it would allow manufacturers to increase production of Vyvanse.

But Kraguljac said having information from the study suggesting higher doses of prescription amphetamines may pose a risk to patients will be helpful to doctors switching their patients' medications.

"It may be really prudent to know that a higher dose of Adderall may put people at additional risk, and to dose accordingly," Kraguljac said.

This article originally appeared on USA TODAY: High doses of Adderall linked to this rare mental health risk: What to know.