“This is a rare but serious side effect that patients, family members, and their doctors should be aware of whenever these medications are prescribed,” says the lead study author, Lauren Moran, MD, MPH, a psychiatrist and pharmacoepidemiology researcher at McLean Hospital in Belmont, Massachusetts.
“Stimulant medications don’t have a dose limit listed 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,” says Dr. Moran.
Limiting Doses May Minimize Risk
For the analysis, Moran and her collaborators reviewed electronic health records for patients in the Mass General Brigham healthcare system between 2005 and 2019, focusing on those ages 16 to 35, the typical age when psychosis or schizophrenia first appear.
The researchers identified more than 1,300 cases of individuals who appeared to have experienced their first episode of psychosis or mania, compared with about 2,800 “control” patients with a psychiatric hospitalization for other conditions, such as depression or anxiety.
When comparing patients’ medication use over the previous month, the scientists discovered that those taking amphetamine-based ADHD drugs had a greater likelihood of psychosis or mania than people who hadn’t taken these drugs over the past month.
The risk was highest in those prescribed 30 milligrams (mg) or more of dextroamphetamine — which is equivalent to 40 mg of Adderall (amphetamine and dextroamphetamine) or 100 mg of Vyvanse (lisdexamfetamine).
Nearly 63 percent of those exposed to any of these medications were at risk of experiencing psychosis or mania. Among those prescribed a high-dose drug, 81 percent were at risk. The findings suggest that among people who take these medications, 8 in 10 cases of psychosis or mania could possibly have been eliminated if they were not on a high dose, according to the study authors.
“Our findings suggest that clinicians can mitigate the risk of psychosis or mania by avoiding doses above 30 mg dextroamphetamine equivalents,” says Moran. “There’s really not a lot of evidence showing that higher doses are effective. There were a couple people in the study who were on 120 mg of Adderall a day — I just don’t understand why people are prescribing such high doses, honestly.”
Evaluating the Risk of Alternative Treatment
Moran and her colleagues also looked at the use of methylphenidate (Ritalin and Concerta) and observed no increased psychosis or mania risk associated with this drug.
This may be because methylphenidate doses were lower than amphetamine doses, according to the analysis.
At high doses, however, methylphenidate may cause problems, according to James Ashworth, MD, the medical director of the Huntsman Mental Health Institute at the University of Utah School of Medicine in Salt Lake City.
“The researchers didn’t really address methylphenidate much in this study,” says Dr. Ashworth, who was not involved in the analysis. “I think high doses of that drug might also precipitate psychosis.”
The Risk Is Relatively Minor, but It’s Not Zero
David Goodman, MD, the director of the Adult Attention Deficit Disorder Center of Maryland and an assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins School of Medicine in Baltimore, stresses that, while these medications are associated with a small risk, they can be very helpful for many ADHD patients.
“This risk is still relatively minor,” says Dr. Goodman, who was not involved in the study. “It’s not zero, but it should not be the factor that leads people to consider whether or not they should treat their ADHD with stimulant medications. People should not jeopardize their treatment based on these results.”
Why Do People With ADHD Take Stimulants?
ADHD is a mental health disorder characterized by a combination of persistent symptoms of difficulty paying attention, hyperactivity, and impulsive behavior. The condition can lead to unstable relationships, poor work or school performance, low self-esteem, and other problems.
