Boston—Although relatively rare, psychosis appears more likely to occur with amphetamine treatment of attention-deficit/hyperactivity disorder (ADHD) than with methylphenidate treatment, according to a new study.

An article in the New England Journal of Medicine points out that prescription use of the stimulants methylphenidate and amphetamine for ADHD therapy has been steadily increasing. In 2007, the study adds, the FDA first required changes to drug labels for stimulants on the basis of findings of new-onset psychosis.

Researchers from Brigham and Women’s Hospital and colleagues note, however, that whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied.

To fill in that information, the study team gathered data from two commercial insurance claims databases to assess patients ages 13 to 25 years who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. Defined as the outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis.

Overall, 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD were assessed, and the study population consisted of 221,846 patients with 143,286 person-years of follow up—110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines.

During the study period, 343 episodes of psychosis—with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication—occurred in the matched populations (2.4 per 1,000 person-years). Of those, 106 episodes (0.10%) were in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% CI, 1.31-2.09).

“Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients,” the study authors concluded. “Amphetamine use was associated with a greater risk of psychosis than methylphenidate. “

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