The chance that a patient on Adderall will have a psychotic or manic episode on even high doses remained quite small — less than 1 percent, Moran said. Nonetheless, she said the study suggested that families of patients on high doses should be watchful for symptoms of psychosis or mania, including hearing voices, having delusions, or talking rapidly.
“I wouldn’t want to cause alarm,” Moran said. “These drugs are very effective, and they help people. This is a rare side effect, but we’re seeing this more often in people taking high doses. It’s just something to look out for.”
The study was published Thursday in the American Journal of Psychiatry.
The researchers found no association between methylphenidate, the generic form of Ritalin, and psychotic or manic episodes. Methylphenidate is the most commonly used drug for ADHD in most countries, but in the United States, amphetamines such as Adderall are prescribed more often.
Adderall is a stimulant whose active ingredient is dextroamphetamine. It doesn’t have an upper dose limit on its drug label, although there’s little evidence that higher doses are more effective than lower doses, according to the study.
The paper said that Adderall triggers the release of the neurotransmitter dopamine, which also happens in patients having psychotic episodes.
Dr. Edward M. Hallowell, an Arlington psychiatrist who has written books on ADHD and has the disorder himself, said he doesn’t doubt an association between high doses of Adderall and rare first-time episodes of psychosis or mania. Nonetheless, he said some patients need high doses, and doctors can prevent psychotic or manic episodes by monitoring patients for signs that something is wrong. Those signs include increased heart rate and blood pressure, decreased appetite, insomnia, and agitation.
“I applaud the study but I take it with the following caveat: There are some few patients who do require a higher dose and for whom it is safe as long as you monitor [them],” he said.
Moran conducted the study amid a surge in prescriptions for amphetamines like Adderall to treat ADHD in the past 20 years.
Among US adults, such prescriptions rose fivefold from 2004 to 2019, according to the researchers. And from 2020 to 2021, during the pandemic, prescriptions rose by as much as 19 percent. Some experts say the latter increase could have stemmed from greater recognition of undiagnosed cases, online marketing of medicines, and over-prescribing by health care providers.
This is not the first time that scientists have drawn a link between stimulants for ADHD and psychosis or mania. In 2006, a review by the Food and Drug Administration resulted in warnings on drug labels to prescribers about an increased risk.
A 2019 study led by Moran also found an association. But that study didn’t explore the relationship between dose amounts and psychiatric hospitalization for psychosis or mania.
Moran’s team sought that answer by reviewing the case studies of 1,374 patients who were admitted to McLean for a first-time psychotic or manic episode from 2005 to 2019. The patients were 16 to 35 years old, the typical age of onset for psychosis and schizophrenia.
The researchers compared that group to 2,748 patients of the same age range who were hospitalized at McLean for other conditions, such as depression and anxiety. Researchers then examined how many of the patients in each group had used the active ingredient in Adderall in the previous month.
The vast majority of patients in both groups hadn’t used Adderall in the prior month. But the researchers calculated that 81 percent of the patients with psychotic or manic episodes who had taken more than 40-milligram doses of Adderall wouldn’t have suffered those episodes without the high doses.
Teva Pharmaceutical Industries Ltd., one of the biggest manufacturers of the generic form of Adderall, declined to comment on the study.
Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.
