High doses of prescription amphetamines associated with risk of psychosis

Teens and young adults who take large amounts of prescription amphetamines may be at more than five times higher risk of developing psychosis or mania, according to a new analysis.

The risk was highest at doses of 30 mg or higher. DextroamphetamineThe researchers concluded that this was equivalent to 40 mg of Adderall. There was no association between new-onset psychosis or mania and past-month Adderall use. Methylphenidate.

“Stimulation “Drug labels do not list upper dose limits, and our findings indicate that dose is clearly a factor in psychosis risk and should be a primary consideration when prescribing stimulants,” lead researcher Lauren Moran, MD, a pharmacoepidemiologist at McLean Hospital in Belmont, Massachusetts, said in a news release.

“This is a rare but serious side effect that should be monitored by both patients and doctors whenever these medications are prescribed,” Moran said.

This study Publish online September 12 American Journal of Psychiatry.

Clear dose-response relationship

Previous studies have identified an increased risk of psychosis with prescription amphetamines, but there is limited information on the effects of dosage levels.

“Given the high prescription rates of this class of medication, this represents a major knowledge gap,” the researchers wrote.

To investigate, Moran and his colleagues used electronic health records of patient visits at Massachusetts General Hospital-Brigham from 2005 to 2019 to conduct a case-control study focusing on individuals between the ages of 16 and 35, the typical age of onset of psychosis.

They identified 1374 case-patients who presented with a first episode of psychosis or mania and 2748 control patients who had been admitted to a psychiatric hospital for other conditions. depression Or anxiety.

Overall, we observed a more than twofold increased odds of psychosis and mania in individuals who had used prescription amphetamines in the past month (adjusted odds ratio [aOR]2.68; 95% CI, 1.90 – 3.77).

The odds of psychosis or mania due to past-month prescription amphetamine use increased 5.3-fold with doses of more than 30 mg dextroamphetamine equivalent, compared with 40 mg and 100 mg mixed amphetamine salts. Lisdexamfetamine.

In a sensitivity analysis comparing cases with outpatient controls, there was a 13.5-fold increase in the odds of psychosis or mania at the highest dose level.

Past-month use of methylphenidate was not associated with increased odds of psychosis or mania compared with no use (aOR, 0.91; 95% CI, 0.54 to 1.55). 2019 Survey By Moran and colleagues.

Risk Mitigation Strategies

In this study, the researchers found that people with attention-deficit hyperactivity disorder (ADHD)ADHD) There is no maximum dose for treatment, and “given the lack of evidence-based studies to support a maximum dose,” clinicians are recommended to aim for a dose that controls symptoms while avoiding intolerable side effects.

“Our findings suggest that clinicians may reduce the risk of psychosis and mania by avoiding doses exceeding 30 mg dextroamphetamine equivalent,” the researchers wrote.

Comment on this study Medscape Medical NewsDr. Steven Faraone, professor emeritus of psychiatry at the State University of New York Upstate Norton School of Medicine in Syracuse, New York, noted that the U.S. Food and Drug Administration has already warned that stimulants can cause psychosis.

“These new data from well-conducted studies are helpful in providing some guidance on dosing,” Faraone said.

However, he noted that most of the study participants did not have ADHD, so it's unclear whether the data applies to the majority of people with the condition.

“We also don't know if the stimulants were being used as prescribed,” Faraone added, “and some of the results may be due to the fact that some patients abuse stimulants.”

Faraone also cautioned that this is an observational study and, like any other, is subject to confounding factors. “The authors appropriately adjusted for available confounders, but did not adjust for unavailable confounders, such as the severity of prior psychiatric disorders,” Faraone said.

Nina Kraglujak, MD, professor in the department of psychiatry and behavioral health at The Ohio State University College of Medicine in Columbus, also commented that she felt the study was done “very carefully” and that the authors “did a very good job of explaining the limitations of the study.”

“But my main learning as a researcher and clinician is that we should be cautious about prescribing high doses of amphetamines to treat ADHD in young people, because high-dose treatment may actually increase the risk of psychosis,” Kraglujak said. Medscape Medical News.

This is especially important if there is a family history of psychosis or other serious mental illness, Kraglujak said, “or opting for an alternative medication like Ritalin.” [methylphenidate] “If you're concerned about someone who has a family history of mental illness, I would encourage them to get this test,” she advised.

The study was funded by a grant from the National Institute of Mental Health. Moran is employed by Sage Therapeutics (which was not involved in the study and will be working with the company after it is completed and submitted for publication). Faraone and Kraglujak said they are not affiliated.