Leucovorin Spike

A number of posts discussed Trump's support for dubious notions about autism.

The history of autism "cures" is a history of dashed hopes and frequent danger

A release from the University of Michigan:

Leucovorin prescriptions for children spiked after federal officials claimed the drug was an effective treatment for autism during a September 2025 press conference, according to a new Michigan Medicine-led study published in The New England Journal of Medicine.

During the highly publicized event, the United States Department of Health and Human Services announced a plan to update leucovorin’s label to include cerebral folate deficiency, a rare genetic condition that can sometimes include symptoms of autism.

At the same time, federal officials also touted leucovorin’s effectiveness for autism, despite limited evidence supporting that claim.

After the press conference, the number of children aged 0-17 with a filled leucovorin prescription increased 46%, from 4.6 children per 100,000 in the week before the conference to 6.7 per 100,000 during the week of the conference, according to the new research.

"Our findings suggest the press conference may have increased off-label prescribing of leucovorin to children with autism,” said lead author Kao-Ping Chua, M.D., Ph.D., a pediatrician and researcher at University of Michigan Health C.S. Mott Children's Hospital and director of the Susan B. Meister Child Health Evaluation and Research Center.

"This increase is concerning because the effectiveness and long-term safety of leucovorin for children with autism is uncertain."

The authors analyzed a database representing nearly all prescriptions filled in U.S. retail pharmacies.

During 2025, the database included 150,026 leucovorin prescriptions dispensed to 47,394 children.

The weekly number of children with filled leucovorin prescriptions rose from 734 to 5,858 children between the beginning and end of 2025 – a 700% jump.

Much of this increase was driven by the spike in leucovorin dispensing after the press conference, and the largest increases were seen among children ages 6 to 11 and in the southern United States.

By comparison, leucovorin dispensing to adults did not spike after the press conference.

Leucovorin, a decades-old version of Vitamin B9, has mainly been used to counter side effects from methotrexate, a drug used in treating cancer and autoimmune conditions.

A handful of small studies have suggested that leucovorin can help improve some autism symptoms in children, but large randomized clinical trials have not been conducted.

By using a comprehensive national database, the new study builds on earlier research that used smaller databases to assess changes in leucovorin prescribing to children after the press conference.

Concerns about increased off-label use

The new research also showed that there was an increase in leucovorin dispensing to children even before the press conference.

The trend may have been driven by national news coverage featuring compelling patient stories that may have increased interest among some families.

Chua says the rise in leucovorin use among children raises several concerns, including the potential to create false hope for families, displace evidence-based therapies and expose young children to a treatment whose effectiveness and long term safety have not been established.

Other researchers have speculated that increased off-label prescribing of leucovorin may have contributed to ongoing drug shortages that have reduced access for cancer patients who depend on the medication.

"Our findings demonstrate the power of the federal government to influence medical practice," Chua said.

"Given this power, it is important that the government’s messaging about medications is based on rigorous evidence.”

Additional authors: Sijia He, M.S. and Rena M. Conti, Ph.D.

Study Cited: "Leucovorin Dispensing to U.S. Children in 2025,” NEJM.

The Leucovorin Surge

A number of posts discussed Trump's support for dubious notions about autism.

The history of autism "cures" is a history of dashed hopes and frequent danger.

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

Our data suggest that leucovorin prescription rates rose sharply following the September 2025 announcement by White House leaders but began a steadier increase in February 2025, after being stable for 2 years. A recent analysis4 reported increased leucovorin prescriptions in children following the White House announcement. Our study extends these findings by examining a longer observation period and restricting the cohort to children with a prior ASD diagnosis, which reveals that the upward trend in prescribing began months before the announcement and was specific to the population of greatest clinical interest.

A February 17, 2025, CBS Evening News segment titled “Parents say off-label drug helped son with autism speak”6 described a family whose child was diagnosed with autism when aged 2.5 years and was prescribed off-label leucovorin when aged 3 years. According to his mother, he spoke his first word within days of starting the medication, and by age 5 years, he had enrolled in a mainstream kindergarten program. Following the CBS segment, the story received substantial media attention, and Autism Speaks, the largest autism nonprofit organization in the US, highlighted the news on their website on February 25, 2025.7

Our findings suggest that mainstream media information about leucovorin’s potential use in ASD and the 2025 announcement by White House leaders may be associated with substantial increases in leucovorin use in children with ASD. Although no large randomized clinical trials have been initiated to assess the safety and efficacy of leucovorin for ASD, an increasing number of patients are being prescribed the medication. Notably, on March 10, 2026, the FDA approved leucovorin for the treatment of cerebral folate transport deficiency due to confirmed FOLR1 gene variants.8 However, the FDA did not approve leucovorin for ASD. This regulatory decision warrants ongoing surveillance of leucovorin prescribing for children with ASD. This study has limitations, including reliance on prescription-level data without confirmation of medical indication, inability to assess patient-level clinical outcomes, and lack of adjustment for site-level variation in Epic Cosmos participation. The rapid increase in leucovorin use for ASD, the timing of which is associated with otherwise exogenous events, may offer a novel natural experiment to better understand the potential behavioral effects of leucovorin in ASD.

 

Acetaminophen Litigation

In The Politics of Autism, I discuss various ideas about what causes the condition. 

If you listen to Sirius XM, you may have heard radio ads about a class action lawsuit alleging that acetaminophen causes it.

But there is a very long and growing list of other correlates, risk factors, and possible causes that have been the subject of serious studies:

Reuters:

The Judicial Panel on Multidistrict Litigation will meet today in St. Louis to consider creating nationwide MDLs for three fast-growing areas of product-liability litigation: social media addiction lawsuits, primarily against Facebook and Instagram’s parent Meta Platforms Inc; claims that acetaminophen use during pregnancy increases the child’s risk of autism-spectrum disorders and ADHD; and cases spurred by Exactech Inc’s recent recalls of many of its knee, ankle and hip-replacement products.

...

MDL No. 3043 − IN RE: ACETAMINOPHEN − ASD/ADHD PRODUCTS LIABILITY LITIGATION Dozens of lawsuits have been filed in the past year, quoting recent studies that link pregnant women’s use of acetaminophen to an increased risk of autism spectrum disorders (ASD) and ADHD in their children. In June, plaintiff Aujenai Thompson sought to consolidate 19 actions against the sellers of “store-brand” acetaminophen products for pretrial coordination or consolidation. Since then, more than 30 related actions have been filed, naming Costco Wholesale Corp, CVS Pharmacy Inc, Rite Aid Corp, Safeway, Target Corp, Walgreen Co and Walmart Inc as defendants.

Compounding Pharmacies

Many parents of ASD children use compounding pharmacies.  The Center for Responsive Politics reports:

COMPOUNDING PHARMACIES BATTLE REGULATION: Compounding pharmacies have been suddenly thrust into the public spotlight after multiple cases of meningitis were traced to steroids mixed -- or compounded -- at a pharmacy in Massachusetts. Compounding pharmacies, which operate differently than regular pharmacies, are a relatively new phenomenon, and the battle over how they're regulated is still being fought.

But the young industry has isn't naive in the ways of Washington. The Wall Street Journal reported yesterday, citing Center for Responsive Politics data, that the International Association of Compound Pharmacies has spent more than $1.1 million since 2000, wrangling with Congress and regulators at the Food and Drug Administration.

As the Journal points out, it's not clear that the current meningitis outbreak would have been prevented by any proposed regulations (or better oversight of current regulations), but a review of lobbying records on OpenSecrets.org shows that the IACP isn't the only group lobbying on compounding pharmacies. In fact at least 30 organizations have filed dozens of lobbying reports in the last decade on the issue of "compounding" -- many of them individual compounding pharmacies, but also a number of pharmaceutical giants with high-octane lobbying operations, like Wyeth, AstraZeneca and Pfizer.

From the Wall Street Journal report:

After regulators including Dr. [David] Kessler called for greater oversight of the industry, Congress in 1997 passed a law that gave the FDA clearer authority to treat them like drug makers. Small pharmacies were exempt from FDA regulation, but those that advertised or solicited business faced greater FDA scrutiny.

In 2001-02, four people died, more than a dozen were injured and hundreds exposed after they received back-pain shots tainted with meningitis dispensed by two pharmacies in California and South Carolina. The pharmacist in charge at the California facility later surrendered his license after state regulators found nonsterile conditions.

Around that time, seven compounding pharmacies filed a lawsuit seeking to peel back the FDA's regulatory powers on the grounds that the provision on advertising violated the First Amendment. In 2002, the Supreme Court struck down the 1997 law in a 5-4 ruling that found the law was an unconstitutional prohibition against commercial free speech.

After that, the FDA tried to regulate the industry by issuing compliance policy guidelines. But those had little effect, attorneys say, because they don't carry the same weight as laws or formal regulations.

When Edward Kennedy and Pat Roberts were working on a new law in 2007, compounding pharmacies mobilized their clients. Reuters reports:

Compounders also enlisted parents of autistic children, who besieged Kennedy's office, arguing that compounding pharmacies were the sole source of treatments for the condition, such as the unproven therapy chelation to remove toxic metals from the body. Kennedy's bill never reached the floor.

The bill's proponents "saw the opposition and decided it wasn't going anywhere," said Fusco Walker.

Autism Drugs

According to Business Week, the pharmaceutical industry is looking at medications for autism.

Diagnoses among children jumped 57% from 2002 to 2006, according to the Centers for Disease Control & Prevention in Atlanta. Roughly 1 in 110 8-year-olds in the U.S. is on the autism spectrum. Just as interesting to drugmakers is the fast-growing population of adult autistics who can't be helped by the kind of intensive behavioral therapy that sometimes works on children, because their brains lack the same plasticity. One decade from now there will be seven times as many autistics entering the adult-services sector as there are today. The disorder already costs the U.S. about $35 billion per year for special education, medical care, and assisted living. If the drug industry can devise better treatments, families and society will find a way to pay

The reporter errs in claiming that behavioral therapy cannot help adults. It may be more effective with children, but adults may benefit, too.