Amphetamine, Methylphenidate ADHD Treatment Linked to Adolescent Psychosis

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Among adolescents and young adults with ADHD receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients.

The use of amphetamine and methylphenidate for the treatment of young people with attention-deficit/hyperactivity disorder (ADHD) was associated with an increased risk for new-onset psychosis, according to results from a study published in the New England Journal of Medicine.

Researchers conducted a retrospective cohort study of 221,846 young people aged 13 to 25 years who were diagnosed with ADHD between 2004 and 2015. Patients were propensity score matched to 1 of 2 treatment groups (methylphenidate or amphetamine; n=110,923 in each), and the incidence of new-onset psychosis was compared between the 2 stimulants. Clinical data were obtained from 2 large, US-based insurance databases, and the results were combined using a fixed-effects meta-analysis.

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After analysis, the researchers found a total of 343 cases of psychosis in the matched treatment groups, which included 237 (0.21%) and 106 cases (0.10%) in the amphetamine and methylphenidate groups, respectively. In addition, they reported that the hazard ratio for psychosis in amphetamine group was 1.65 (95% CI, 1.31-2.09).

One key limitation of the study was the presence of unmeasured confounding factors; another was that the findings were not generalizable to patients who have public insurance or no insurance.

“[T]he risk of new-onset psychosis was approximately 1 in 660 patients who received a prescription for stimulants for ADHD, but the risk was about twice as high among patients who started amphetamine as among patients who started methylphenidate,” the researchers wrote.

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Moran LV, Ongur D, Hsu J, et al. Psychosis with methylphenidate or amphetamine in patients with ADHD. N Engl J Med. 2019;380(12):1128-1138.