Yoshi Rothman, MD, talks rise in leucovorin prescriptions for autism

This is part 1 in a 2-part series on rising leucovorin prescribing rates for autism. Check back on May 21 for part 2.

A new study published in JAMA Network Open found that prescriptions for leucovorin among children with autism spectrum disorder (ASD) increased sharply following national media coverage and a September 2025 White House announcement promoting the drug for speech-related deficits associated with autism.¹

Investigators from the University of California San Diego School of Medicine analyzed prescribing trends using Epic Cosmos electronic health record data representing more than 300 million patient records from hospitals and clinics across the United States. The study included 838,801 pediatric patients with ASD and more than 11.9 million outpatient encounters between January 2023 and January 2026.

Researchers found that leucovorin prescription rates remained relatively stable for 2 years before increasing steadily beginning in early 2025. Rates rose from a monthly mean of 34.1 prescriptions per 100,000 outpatient encounters between January 2023 and January 2025 to 335.2 prescriptions per 100,000 encounters in August 2025. By November 2025, prescription rates had climbed to 835.4 per 100,000 encounters, representing an increase of more than 24-fold compared with earlier baseline rates.

The study authors noted that the increase accelerated after a September 2025 announcement from President Donald Trump and Health and Human Services Secretary Robert F. Kennedy Jr., promoting leucovorin as a treatment for speech-related deficits associated with ASD. However, prescribing rates had already begun increasing months earlier.

In an interview with Contemporary Pediatrics, lead author Yoshi Rothman, MD, assistant professor of pediatrics at the University of California San Diego School of Medicine, said the findings surprised investigators because the upward trend predated the White House announcement.

“What we observed was that the rates of prescriptions increased by over 2,000% for children with autism, but what we were surprised to find was that those prescriptions actually started increasing even prior.”

According to the study, investigators linked the earlier increase to a February 2025 national television news segment describing a child with autism who reportedly began speaking after treatment with off-label leucovorin. The story subsequently received substantial media attention and was highlighted by Autism Speaks later that month.

Leucovorin, also known as folinic acid, is a reduced form of folic acid. Prior small clinical trials have suggested potential improvement in verbal communication among some children with autism and folate deficiency who receive the therapy, although large-scale randomized trials confirming safety and efficacy for ASD have not been completed.

Rothman said the findings reflect how frequently families encounter treatment information through social media and news outlets before discussing it with healthcare professionals.

“As a pediatrician, I have families come in all the time, and they ask me, ‘I saw this on social media,’ or ‘I saw this on TikTok or Instagram,’ and they always ask for my opinion,” Rothman said. “I think that the medical community is starting to take this much more seriously, that we need to be aware of what our patients are seeing on social media and on the news media, because we are going to be helping them to make decisions based on what is being brought forth.”

The investigators also noted that although the US Food and Drug Administration approved leucovorin in March 2026 for cerebral folate transport deficiency associated with confirmed FOLR1 gene variants, the therapy has not been approved for ASD.²

Rothman emphasized that pediatricians should continue supporting families as they navigate treatment decisions.

“As any pediatrician or any health care provider would say, we all want to support our patients, and we all want our patients to feel that we are listening to them, and we're trying to help them as best we can,” Rothman said. “We need to be there for our patients to help them make some of these really difficult decisions.”

References

1. Rothman JM, Kwan B, Longhurst CA, Jena AB. Rates of leucovorin prescriptions for children with autism. JAMA Netw Open. 2026;9(5):e2613286. doi:10.1001/jamanetworkopen.2026.13286

2. FDA. FDA Approves First Treatment for Patients with Cerebral Folate Transport Deficiency. FDA. March 10, 2026. Accessed May 20, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency