The number tells the story before anything else does. In November 2025, American doctors were writing leucovorin prescriptions for children with autism at a rate of 835 per 100,000 outpatient encounters. Two years earlier, that figure sat at 34. No new drug approval had happened. No breakthrough clinical trial had reported. What changed, researchers at UC San Diego now argue, was the news cycle, and then the White House.
Their study, published this week in JAMA Network Open, is perhaps the most striking recent illustration of a phenomenon that keeps worrying clinicians: that the prescription pad can follow the press release, sometimes by months, sometimes by years, before the evidence arrives to justify it.
From One Family’s Story to a National Trend
Leucovorin, also known as folinic acid, is a biologically active reduced form of folic acid that has been used for decades in oncology, mostly to reduce the toxic effects of chemotherapy drugs like methotrexate. Its potential role in autism is newer and considerably more contested. Small clinical trials have suggested that some children with autism and folate-related deficiencies may show improvements in verbal communication after taking the drug. The key word, researchers are careful to point out, is “some.” The evidence is suggestive, not settled; the patient subgroup it might help has not been precisely defined; and large randomised controlled trials have not been done.
What happened next reads a bit like a case study in how medical information moves in the social media age. On February 17, 2025, a CBS Evening News segment featured a family whose child, diagnosed with autism at age two and a half, had reportedly spoken his first word within days of starting leucovorin at age three. By age five, according to his mother, he had enrolled in mainstream kindergarten. The segment was arresting television. Within days it had ricocheted across social media; by February 25, Autism Speaks, the largest autism nonprofit in the United States, had highlighted the story on its website.
The prescribing data, drawn from the Epic Cosmos database covering more than 300 million patient records across 1,800-plus hospitals and over 41,500 clinics in all 50 states, shows a clear inflection around that point. After roughly two stable years at a monthly mean of about 34 prescriptions per 100,000 encounters among children with autism, rates began climbing steadily in February 2025. That is, months before the White House said a word about it.
Then the Government Stepped In
On September 22, 2025, the trend entered a different register entirely. President Trump and Health and Human Services Secretary Robert F. Kennedy Jr. publicly promoted leucovorin as a potential treatment for speech-related deficits in autism. Within weeks, prescribing rates had surged again. By November, the figure had cleared 835 per 100,000 encounters, a more than 24-fold increase against the 2023-2025 baseline. “The timing was striking,” said Joshua Rothman, a clinical assistant professor of pediatrics at UC San Diego who led the study. “The increases began after a widely viewed media story and accelerated again after federal officials publicly discussed the medication. It highlights how rapidly clinical practice can shift when a treatment captures public attention.”
The researchers are clear that their study does not tell us whether leucovorin actually helps children with autism. It cannot. The dataset tracks prescriptions, not outcomes; there is no way, from these records alone, to know whether the children who received the drug improved, worsened, or showed no change. What the data does show, with some precision, is the mechanism by which public information, filtered through television and government endorsement, translated into clinical behaviour at a national scale.
A Natural Experiment Nobody Planned
“Families of children with autism are often searching for therapies that might improve communication and quality of life, especially when treatment options are limited,” Rothman said. “What this study shows is how quickly information shared through news coverage, social media and public figures can influence real-world prescribing patterns, even before large clinical trials establish whether a treatment is truly safe and effective for broad use.” The cohort in this study included 838,801 children with autism, accounting for nearly 12 million outpatient encounters. Among those prescribed leucovorin, about 53 percent were aged five to eleven; the sex distribution (roughly 77 percent male) tracked the known demographics of autism diagnosis. These are, in other words, real patients, many of them quite young, whose doctors were making decisions in the absence of robust randomised evidence.
There is a wrinkle worth noting. In March 2026, the FDA did approve leucovorin, but for a different condition entirely: cerebral folate transport deficiency caused by confirmed FOLR1 gene variants, an ultra-rare genetic neurological disease. The drug was not approved for autism spectrum disorder. That distinction matters because the FDA’s decision creates an ambiguity in the landscape: leucovorin now has legitimate regulatory standing for a related-sounding but genetically specific indication, which may make it easier to justify off-label prescribing in clinical conversations, even where the evidence for broader use in autism remains thin.
Rothman and his colleagues frame the situation with the measured optimism of researchers who see opportunity in a mess. “We now have a real-world example of how public attention can accelerate adoption of a therapy before the evidence fully catches up,” he said. The prescription surge, whatever its clinical wisdom, has effectively created a large uncontrolled population of children receiving leucovorin, one that could, in principle, serve as the foundation for observational studies of the kind that might help answer the underlying question. The next step, Rothman argues, is generating rigorous trial data so that families and clinicians can make genuinely informed decisions, rather than ones shaped by what was on the news last February.
Whether that evidence will arrive before the attention fades is, of course, another matter. Medical fashions have their own half-lives. The more durable question this study raises is how medicine should respond when public information, not peer review, sets the pace.
https://doi.org/10.1001/jamanetworkopen.2026.13286
Frequently Asked Questions
Is leucovorin approved to treat autism?
No. As of early 2026, leucovorin has not been approved by the FDA for autism spectrum disorder. In March 2026, the agency did approve it for a specific rare genetic condition, cerebral folate transport deficiency, but that is a distinct diagnosis from autism. Prescribing leucovorin for autism remains off-label, meaning doctors can do it but without the evidentiary backing that formal approval requires.
What is the actual evidence that leucovorin helps children with autism?
The evidence is limited and preliminary. Small clinical trials have suggested some children with autism who also have folate-related deficiencies may experience improvements in verbal communication. However, large randomised controlled trials confirming the drug’s safety and effectiveness for broad use in autism have not been completed, which is why researchers are calling for more rigorous studies before widespread prescribing continues.
Why did prescriptions rise so dramatically before the White House made any announcement?
The data suggests that a February 2025 CBS Evening News segment, which featured a family reporting dramatic language improvements in their autistic child after leucovorin treatment, was enough to begin shifting prescribing patterns nationally. That rise preceded the White House promotion by about seven months, illustrating how powerful mainstream media coverage alone can be in shaping clinical practice, even without government endorsement.
Could this rapid uptake lead to safety problems?
Leucovorin is generally considered low-risk, but the study’s authors stress that large-scale safety data specific to children with autism taking the drug long-term does not yet exist. The concern is not that leucovorin is known to be harmful, but that a 24-fold increase in prescribing has outrun the evidence base needed to know who benefits, who might not, and at what doses. That gap between uptake and evidence is what the researchers want clinical trials to close.
What makes this situation a “natural experiment”?
Because the surge in prescribing was triggered by external events (a news segment, a government announcement) rather than by any planned clinical study, researchers can treat the before-and-after pattern as a kind of accidental trial. The large number of children now receiving leucovorin, combined with national electronic health records, could in principle allow scientists to compare outcomes between those who received the drug and those who did not, generating real-world evidence that might help answer the fundamental clinical question.
ScienceBlog.com has no paywalls, no sponsored content, and no agenda beyond getting the science right. Every story here is written to inform, not to impress an advertiser or push a point of view.
Good science journalism takes time — reading the papers, checking the claims, finding researchers who can put findings in context. We do that work because we think it matters.
If you find this site useful, consider supporting it with a donation. Even a few dollars a month helps keep the coverage independent and free for everyone.