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Common ADHD drugs may increase psychosis risk in teens, young adults
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Data from a large study of national health care claims databases revealed that new-onset psychosis occurred in about one in 660 patients aged 13 to 25 years receiving prescription stimulants; however, the risk for psychosis was greater among those prescribed amphetamine than those prescribed methylphenidate.
“There is not a lot of research comparing the safety profiles of amphetamines and methylphenidate, despite increasing use of these medications," Lauren V. Moran, MD, from the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, and the division of psychotic disorders at McLean Hospital, said in a press release.
Although the FDA mandated that manufacturers change drug labels of stimulants to add warnings of the association with new-onset psychosis in 2007, the risk for psychosis in teenagers and young adults with ADHD differs among different stimulants and remains largely unknown, Moran and colleagues wrote in The New England Journal of Medicine.
Using data from two U.S. commercial insurance claims databases — Optum Clinformatics and IBM MarketScan — researchers examined whether patients aged 13 to 25 years with ADHD who started taking methylphenidate or amphetamine received a new diagnosis of psychosis for which an antipsychotic was prescribed within the first 60 days of onset. They matched patients who received methylphenidate with patients who received amphetamine in both databases, compared psychosis incidence between the two stimulant groups and pooled the results to determine HRs for psychosis.
Overall, 337,919 patients received a prescription stimulant for ADHD. The study population included 221,846 patients (143,286 person-years of follow up), with 110,923 patients in each stimulant group.
Moran and colleagues found that 343 episodes of psychosis occurred across the two databases: 106 episodes (0.1%) among those taking methylphenidate and 237 episodes (0.21%) among those taking amphetamine. Analysis revealed that amphetamine use was associated with a greater risk for psychosis than methylphenidate use (pooled HR = 1.65; 95% CI, 1.31-2.09).
In addition, the incidence rate of psychosis was 1.78 episodes per 1,000 person-years of drug exposure in the methylphenidate group compared with 2.83 episodes in the amphetamine group, according to the results.
Post hoc analyses also revealed an increased risk for psychosis with amphetamine use than with methylphenidate use among patients treated by family/internal medicine physicians and pediatricians, but not among those treated by psychiatrists. However, the researchers cautioned that the post hoc nature of the analyses and the inadequate power limit these findings.
“Patients referred to psychiatrists for ADHD may have cognitive deficits or behavioral features that are related to prodromal psychosis, and data on prodromal symptoms would not be captured in claims data. Psychosis may develop in these patients regardless of stimulant treatment,” they wrote. “Alternatively, psychiatrists may prescribe amphetamine more cautiously than other providers and may screen for risk factors for psychosis.” – by Savannah Demko
Disclosure: Moran reports grant support from the NIMH. Please see the study for all other authors’ relevant financial disclosures.