Leucovorin prescriptions for children with autism surged twenty-fourfold after remaining stable for two years, according to a research letter published May 18 in JAMA Network Open.
The study analyzed EHR data from Epic Cosmos, which includes more than 300 million patient records from more than 1,800 hospitals and 41,500 clinics, as of January. Researchers from the University of California San Diego School of Medicine examined 838,801 children with autism spectrum disorder who accounted for 11.9 million outpatient encounters between Jan. 1, 2023, and Jan. 31, 2026.
Here are four things to know:
- Researchers found leucovorin prescription rates rose from a monthly mean of 34.1 prescriptions per 100,000 outpatient encounters between January 2023 and January 2025 to 835.4 prescriptions per 100,000 encounters in November 2025.
- The prescribing increase accelerated after September 2025 when President Donald Trump and HHS Secretary Robert F. Kennedy Jr. publicly promoted leucovorin as a treatment for speech-related deficits associated with autism spectrum disorder.
- Researchers also identified an earlier rise beginning in February 2025 after a CBS News segment highlighted a child with autism who reportedly began speaking after receiving off-label leucovorin treatment.
- No large randomized clinical trials have confirmed leucovorin’s safety or efficacy for autism spectrum disorder. Although the FDA approved leucovorin in March for cerebral folate transport deficiency tied to confirmed FOLR1 gene variants, the agency did not approve the drug for autism spectrum disorder.
Study limitations include reliance on prescription-level data without confirmation of medical indication, inability to assess patient-level clinical outcomes and lack of adjustment for site-level variation in Epic Cosmos participation.
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