People who are taking high doses of Adderall face an increased risk for developing psychosis or mania, according to a new Mass General Brigham study.
The researchers from McLean Hospital, a psychiatric teaching hospital, found that high doses of the prescription amphetamine were linked to a five-fold elevated risk of new-onset psychosis or mania.
The psychosis and mania risk was highest in those taking 30 mg or more of dextroamphetamine, which corresponds to 40 mg of Adderall.
“Stimulant medications don’t have an upper dose limit on their labels, and our results show that it is clear that dose is a factor in psychosis risk and should be a chief consideration when prescribing stimulants,” said lead study author Lauren Moran, a pharmacoepidemiology researcher at McLean Hospital.
Moran said the study was motivated by her past clinical observations as an inpatient psychiatrist. She and her McLean colleagues regularly saw patients experiencing first episodes of psychosis, and their medical records revealed they were prescribed high doses of stimulants by their doctors.
The researchers looked at nearly 15 years of emergency department admissions across Mass General Brigham hospitals.
Among people who take prescription amphetamine, 81% of cases of psychosis or mania could have been eliminated if they were not on the high dose, the scientists found.
“This is a rare but serious side effect that should be monitored by both patients and their doctors whenever these medications are prescribed,” Moran said.
While a significant dose-related risk increase was seen in patients taking high doses of amphetamine, no significant increase was seen with methylphenidate (Ritalin) use.
Moran said the findings shouldn’t create alarm, but should lead to extra caution when these medications are prescribed — especially for those who have risk factors for psychosis and mania.
“There’s limited evidence that prescription amphetamines are more effective in high doses,” Moran said. “Physicians should consider other medications our study found to be less risky, especially if a patient is at high risk for psychosis or mania.”
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Researchers reviewed electronic health records of Mass General Brigham patient encounters between 2005 and 2019, focusing on adults aged 16 to 35, the typical age of onset for psychosis and schizophrenia.
All patients were admitted to McLean Hospital following referrals from other hospitals in the Mass General Brigham healthcare system.
The researchers identified 1,374 cases of individuals presenting with first-episode psychosis or mania, compared to 2,748 control patients with a psychiatric hospitalization for other conditions like depression or anxiety.
They conducted a comparison analysis of stimulant use over the preceding month, and accounted for other factors, including substance use, in order to isolate the effects of stimulants.
The scientists found that among people who take prescription amphetamine, 81% of cases of psychosis or mania could have been eliminated if they were not on the high dose.
Prescribing rates for stimulants that treat attention-deficit/hyperactivity disorder (ADHD) have increased significantly over the past decade, with some of the largest increases reported during the COVID pandemic.
