Leucovorin Scripts Surged Even Before White House Autism Push

Prescriptions for leucovorin for children with autism rose sharply after widespread media attention early in 2025, and again after a White House briefing last fall promoted unproven claims about the drug, an analysis of national electronic health record data showed.

After remaining stable for 2 years, leucovorin prescription rates climbed from a monthly average of 34.1 prescriptions per 100,000 encounters between January 2023 and January 2025 to 335.2 prescriptions per 100,000 encounters in August 2025, reported Joshua Rothman, MD, of the University of California San Diego School of Medicine, and colleagues.

In November 2025, rates surged again to 835.4 prescriptions per 100,000 encounters, more than 24 times higher than the 2023-2025 monthly mean, Rothman and co-authors noted in JAMA Network Open. Prescription rates plateaued in December 2025 and January 2026 but remained elevated.

The initial increase in prescribing followed a February 2025 national CBS News segment featuring a family who reported dramatic language improvements in a child after treatment with leucovorin, the researchers said.

Interest grew further after White House officials promoted leucovorin in September 2025 as part of broader autism-related initiatives, they added.

This March, the FDA reversed the White House stance on leucovorin, saying there was insufficient evidence that the drug would benefit children with autism. Instead, it approved the drug to treat FOLR1-related cerebral folate transport deficiency, an ultra-rare hereditary disorder.

Leucovorin, also known as folinic acid, is a type of folate used with cancer drugs like methotrexate to counteract their toxic effects. It can cross into the brain even when folate transport is impaired, but researchers maintain that there is no substantive evidence that cerebral folate deficiency plays a role in the pathogenesis of autism.

“We pursued this study to understand leucovorin prescribing patterns for children with autism after the White House announcement. We were surprised to find that prescriptions for leucovorin were rising even prior to the White House announcement,” Rothman told MedPage Today.

“While leucovorin prescriptions for children with autism are on the rise, we still don’t have large randomized trials and long-term follow-up to establish safety and efficacy,” he pointed out. “It is our duty as scientists and clinicians to generate the rigorous data needed to help families and clinicians make informed decisions.”

Earlier research led by Jeremy Faust, MD, MS, of Brigham and Women’s Hospital and Harvard Medical School in Boston, showed that leucovorin prescriptions for children ages 5 to 17 years rose by 71% after the White House briefing compared with what was expected. (Faust is the editor-in-chief of MedPage Today.)

“This new paper shows that media interest alone can drive major interest in the public,” Faust noted. “And it reaffirms what we found, which was that the White House press event in September amplified that further.”

The February 2025 CBS Evening News segment, “Parents say off-label drug helped son with autism speak,” featured a family whose child was diagnosed with autism at age 2.5 and prescribed off-label leucovorin at age 3, Rothman and colleagues said. His mother reported that he spoke his first word within days of starting the medication and enrolled in a mainstream kindergarten program by age 5. The report received substantial media attention, the researchers said.

Subsequent CBS News print coverage was “cautious about evidence gaps, dosing uncertainty, supply problems, and the commercial interests now forming around this drug,” noted journalist Celine Gounder, MD, who reported the story.

“This paper is a useful reminder that medical journalism shapes prescribing, that broadcast and print mediums have a tangible impact on how patients and clinicians understand the evidence, and that there is a responsibility to continue revisiting and reporting on stories after the first segment airs,” Gounder told MedPage Today.

For the current study, Rothman and colleagues analyzed records from the Epic Cosmos database, which included more than 300 million patient records from over 1,800 hospitals and 41,500 clinics across all 50 states and Washington, D.C. The study focused on 838,801 children with autism who accounted for more than 11.9 million outpatient encounters from January 2023 through January 2026.

The rapid increase in leucovorin prescribing may offer a novel natural experiment to understand the potential behavioral effects of the drug in autism, the researchers said.

“Families are desperate to help their children with autism spectrum disorder,” observed Audrey Brumback, MD, PhD, of the University of Texas at Austin, who wasn’t involved with the study.

“Clinicians and families develop treatment plans for our patients through shared decision-making,” she told MedPage Today. “As clinicians, we look to guidelines from trusted sources like our professional organizations and read primary literature to understand the risks and benefits of specific treatments. Families tell us they, too, have done their own research,” she added.

When there’s disagreement about treatments, “we use ethical frameworks such as the zone of parental discretion to make holistic decisions about the patient’s health, which includes maintaining the therapeutic relationship with the family,” Brumback said. “Clearly, in this case, clinicians saw the net risk/benefit ratio lean toward prescribing the requested treatment, even though it lacks evidence.”