A recent study indicates a dramatic increase in leucovorin prescriptions for children in the US after a publicised government endorsement, raising concerns over off-label use amidst limited evidence of efficacy for autism.
A study in the New England Journal of Medicine has found that leucovorin prescriptions for children in the US rose sharply in 2025 after the Trump administration publicly promoted the drug as a possible autism treatment. The researchers said the pattern suggests the White House announcement may have driven off-label use, even though evidence for the drug in autism remains uncertain.
Leucovorin, a folic acid analogue, is already used to ease side effects from methotrexate, a medicine prescribed for some cancers and autoimmune diseases. The US Food and Drug Administration has said it can be used in children with cerebral folate deficiency, a rare disorder that can resemble autism, but it is not approved to treat autism itself. In commentary on earlier research, Brown University’s Michael Barnett and Jeremy Faust of Mass General Brigham said the condition can mimic autistic symptoms.
The NEJM team examined retail pharmacy data covering about 93% of US prescriptions and tracked trends from late December 2024 through mid-December 2025. They found that prescriptions for children increased from 1.0 per 100,000 to 4.6 per 100,000 before the press conference, then climbed a further 46% afterwards to 6.7 per 100,000. By the end of the study period, the rate had reached 8.0 per 100,000. In total, 47,394 children received 150,026 leucovorin prescriptions in 2025, with a weekly count rising from 734 children to 5,858, a sevenfold increase. The sharpest growth was seen among children aged six to 11 in the southern US, while adult prescribing did not change.
Lead author Kao-Ping Chua said in a press release from the University of Michigan School of Public Health that the findings suggest the federal announcement may have increased prescribing and that the safety and effectiveness of leucovorin for autistic children remain unclear. Advocacy groups have warned that the message from Washington could mislead families at a time when the evidence base is still weak. Zoe Gross of the Autistic Self Advocacy Network told CIDRAP News that parents need government guidance grounded in science, not what she described as a push towards a treatment that probably does not work. The American Academy of Paediatrics says more research is needed to determine who, if anyone, might benefit and whether the drug is safe and effective.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
