Summary: A national electronic health record analysis shows how quickly public attention can change real-world medical practice before large randomized trials confirm a treatment’s benefit. Reviewing records for more than 838,000 children with autism spectrum disorder (ASD), researchers identified a dramatic rise in prescriptions for leucovorin (folinic acid), an off-label treatment sometimes used for autism, with prescribing rates increasing by over 2,000% during the study period.
The surge in use closely followed a widely viewed national television news story and later public endorsements by White House officials, underscoring the strong influence of media coverage and political statements on clinical prescribing behavior.
Key Facts
- Massive increase in prescriptions: Leucovorin prescribing rose from an average of about 34 prescriptions per 100,000 outpatient encounters to more than 835 per 100,000 encounters, an increase exceeding 2,000%.
- Media-driven change: Rates began to climb in February 2025 after a national television segment featured a family reporting marked language gains in their child following leucovorin treatment.
- Accelerated by public statements: The upward trend accelerated after September 2025 when federal officials publicly referenced leucovorin during autism-related initiatives.
- Large dataset: The analysis used the Epic Cosmos database and included 838,801 children with autism across more than 11.9 million outpatient encounters from January 2023 through January 2026.
- Regulatory status: In March 2026 the U.S. Food and Drug Administration approved leucovorin for cerebral folate transport deficiency, an ultra‑rare genetic neurological disorder; the drug remains unapproved for routine use in ASD.
Source: UCSD
Study overview
Researchers at the University of California San Diego examined national electronic health records to quantify how prescribing patterns for leucovorin changed over time among children diagnosed with autism spectrum disorder. The findings, published May 18, 2026 in JAMA Network Open, show prescribing rates rose more than twentyfold compared with prior baseline levels.
Joshua Rothman, MD, clinical assistant professor of pediatrics at UC San Diego School of Medicine and first author of the study, noted that families of children with autism often explore new treatments in hopes of improving communication and quality of life. “This study demonstrates how rapidly information circulated through news, social media and public figures can affect prescribing before large-scale clinical evidence is available,” he said.
Leucovorin (folinic acid) is a biologically active form of folate. Small, targeted clinical studies have suggested that a subset of children with ASD who have folate-related metabolic differences may experience gains in verbal communication after folinic acid supplementation. However, larger randomized trials assessing efficacy and long-term safety in the broader ASD population are lacking.
Using Epic Cosmos—an aggregated electronic health record resource containing data from over 300 million patients across more than 1,800 hospitals and 41,500 clinics—the team identified 838,801 children with autism and tracked more than 11.9 million outpatient visits from January 2023 to January 2026. For roughly two years prior to 2025, leucovorin prescribing was stable at about 34 prescriptions per 100,000 encounters among children with ASD. Beginning in early 2025, prescribers increasingly ordered the medication, with a major jump by August 2025 to 335 prescriptions per 100,000 encounters and a further rise to over 835 per 100,000 encounters by November 2025.
The timing of these increases corresponded with media and political events. The first uptick followed a February 2025 television story highlighting a family’s experience; the rise accelerated after September 2025 when federal officials publicly mentioned leucovorin during autism-related policy discussions.
The authors emphasize that this observational analysis does not assess clinical outcomes or prove that leucovorin improves ASD symptoms. The database records prescriptions but cannot always confirm the precise clinical indication for every prescription. Still, the rapid rise in use raises important questions for clinicians, families, policymakers and researchers about how public attention shapes treatment uptake before robust evidence is available.
The investigators call for continued monitoring of prescribing patterns and for large, randomized clinical trials to determine whether leucovorin benefits specific groups of children with autism and to establish its safety profile in that population.
“This is a clear, real-world example of how quickly clinical practice can shift when a therapy gains public attention,” Rothman said. “The next step is to generate rigorous data so families and clinicians can make informed treatment decisions.”
Additional co-authors include Brian Kwan, MD, and Christopher Longhurst, MD, from UC San Diego, and Anupam Jena, MD, PhD, from Harvard. The study reported no external funding. Disclosures note that Dr. Jena has received personal fees from various media and consulting organizations and serves as an unpaid board member of the United Network for Organ Sharing; no other conflicts were reported.
Key Questions Answered:
A: Leucovorin, also called folinic acid, is an active form of folate. It attracted attention because small studies indicated that a narrowly defined subgroup of children with autism who have folate-related metabolic differences might show improvements in verbal communication after treatment. However, those findings have not been validated in large, definitive trials across the broader ASD population.
A: No. This research analyzed prescribing trends in electronic health records and did not measure clinical outcomes or symptom changes after treatment. Its purpose was to document how public attention affects prescribing behavior.
A: Prescribing a medication for an unapproved indication—known as off-label use—is common and not illegal. The FDA approved leucovorin in March 2026 for cerebral folate transport deficiency, a distinct ultra‑rare genetic condition. It is not approved for ASD, and because large-scale safety and efficacy trials for ASD are not complete, clinicians and families face uncertainty about long-term effects when using it for autism.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal article was reviewed in full by our editors.
- Staff added contextual details for clarity.
About this autism and pharmacology research news
Author: Lizelda Lopez
Source: UCSD
Contact: Lizelda Lopez – UCSD
Image: The image is credited to Neuroscience News
Original Research: Open access. “Rates of Leucovorin Prescriptions for Children With Autism” by Joshua M. Rothman, Brian Kwan, Christopher A. Longhurst, and Anupam B. Jena. JAMA Network Open. DOI: 10.1001/jamanetworkopen.2026.13286
Abstract
Rates of Leucovorin Prescriptions for Children With Autism
On April 10, 2025, U.S. Health and Human Services Secretary Robert F. Kennedy, Jr. stated at a Cabinet meeting that “in September, we will know what has caused the autism epidemic.” On September 22, 2025, federal officials publicly promoted leucovorin as a potential treatment for speech-related deficits in autism spectrum disorder, timing that the study authors note corresponded with marked increases in prescribing observed in national electronic health record data.