Summary: A national analysis shows how quickly public attention can change medical practice long before large clinical trials confirm a treatment’s value. Using electronic health records for more than 838,000 children with autism spectrum disorder (ASD), researchers found a dramatic rise in prescriptions for leucovorin (folinic acid), an off-label therapy sometimes used for autism—an increase exceeding 2,000% that closely tracked high-profile media coverage and public statements from White House officials.
The surge began after a widely viewed national television news segment and escalated further following public promotion of the drug by federal officials, illustrating the powerful influence of media and political messaging on clinical prescribing patterns.
Key Facts
- Massive increase: Prescriptions for leucovorin rose from a baseline average near 34 per 100,000 outpatient encounters to more than 835 per 100,000 encounters—an increase of over 2,000%.
- Media trigger: Rates started climbing in February 2025 after a national TV story that featured a family reporting marked language gains in their child attributed to the drug.
- Public endorsement: The increase accelerated after September 2025 when White House officials publicly discussed leucovorin as part of federal autism initiatives.
- Large dataset: The analysis used the Epic Cosmos database and covered 838,801 children with ASD and more than 11.9 million outpatient encounters across the United States.
- Regulatory status: In March 2026 the U.S. Food and Drug Administration (FDA) approved leucovorin for an ultra-rare genetic disorder, cerebral folate transport deficiency, but it is not approved for treating autism.
Source: UCSD
Study overview
Researchers at the University of California San Diego examined national electronic health record data to document trends in leucovorin prescribing for children diagnosed with ASD. The peer-reviewed study, published May 18, 2026 in JAMA Network Open, found prescribing rates rose more than 2,000% compared with prior years, with distinct inflection points that coincided with major media exposure and later public statements from federal officials.
“Families of children with autism frequently look for therapies that could improve communication and quality of life, especially when available treatments are limited,” said Joshua Rothman, MD, clinical assistant professor of pediatrics at UC San Diego School of Medicine and first author of the study. “This work shows how quickly news stories, social media and statements by public figures can shift real-world prescribing—long before large randomized trials establish safety and effectiveness.”
About leucovorin (folinic acid)
Leucovorin, also called folinic acid, is an active form of folate. Small, targeted clinical studies have suggested that some children with autism who have specific folate-related metabolic or transport abnormalities may show improvements in verbal skills after treatment. However, large-scale trials that would confirm the drug’s effectiveness and safety for children with ASD at large have not been completed.
Methods and findings
The investigators used records from the Epic Cosmos database, which aggregates more than 300 million patient records from over 1,800 hospitals and 41,500 clinics nationwide. The analysis focused on 838,801 pediatric patients with ASD who accounted for over 11.9 million outpatient visits between January 2023 and January 2026.
For roughly two years prior to 2025, leucovorin prescribing remained steady at about 34 prescriptions per 100,000 outpatient encounters for children with autism. Beginning in early 2025, rates rose steadily and then surged later that year: by August 2025 rates reached about 335 prescriptions per 100,000 encounters, and by November 2025 they exceeded 835 per 100,000 encounters.
The initial rise closely followed a February 2025 national television segment that highlighted a family reporting dramatic language gains after treatment. The trend accelerated again after September 2025 when White House officials publicly discussed leucovorin within autism-related policy announcements.
Limitations and interpretation
The study was designed to describe prescribing patterns and did not measure patient outcomes or determine whether leucovorin improved autism symptoms. The authors also note that prescription records in the database may not always include a clearly documented medical indication. Thus, the research cannot establish benefit or harm; rather, it provides evidence of how public attention influences clinical behavior.
Implications
The rapid adoption of leucovorin for children with ASD raises important questions for clinicians, policymakers and families. The authors call for ongoing monitoring of prescribing trends and for large, randomized clinical trials to assess whether leucovorin benefits specific subgroups of children with autism and to define its long-term safety profile.
“This is a real-world example of how public focus can accelerate use of a therapy before rigorous evidence is available,” Rothman said. “The priority now is to generate high-quality data so families and clinicians can make informed decisions.”
Study contributors and disclosures
Additional co-authors include Brian Kwan, MD, and Christopher Longhurst, MD (UC San Diego), and Anupam Jena, MD, PhD (Harvard). The study received no outside funding. Disclosures: Jena reported personal fees from several organizations and media outlets and an unpaid board role with the United Network for Organ Sharing; no other disclosures were reported.
Key Questions Answered:
A: Leucovorin (folinic acid) is an active form of folate. Interest grew after small studies suggested that a narrowly defined subgroup of children—those with autism plus specific folate-related metabolic or transport issues—might have improved verbal communication after treatment. However, broader, definitive trials demonstrating safety and effectiveness for children with ASD have not been completed.
A: No. The study measured prescribing patterns using electronic health records and did not track patient-level outcomes or determine whether children improved or worsened after receiving leucovorin.
A: It is not illegal to prescribe a medication off-label, and clinicians commonly do so. The FDA approved leucovorin in March 2026 only for cerebral folate transport deficiency, an ultra-rare genetic neurological disorder, not for ASD. Because rigorous trials in children with autism are lacking, clinicians and families lack comprehensive evidence about long-term safety and effectiveness in this population.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was provided by staff.
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, the U.S. Health and Human Services Secretary made public remarks about ongoing investigations into autism. On September 22, 2025, federal officials publicly mentioned leucovorin in the context of speech-related deficits associated with autism spectrum disorder (ASD). The study documents timing and magnitude of prescribing changes that followed these and other public events.