You’ve probably seen the headlines. The FDA announced it’s expanding the label on a drug called leucovorin so it can be used for children with autism-related symptoms. For parents who have been searching for answers, this feels big. But what does it actually mean, and is it right for your child?
This article breaks down what’s happening, what the research shows, and how to make sense of it all.
The Short Answer
Leucovorin is a prescription form of folate (vitamin B9) that helps deliver this nutrient directly to the brain. The FDA is updating the drug’s label to include treatment for cerebral folate deficiency (CFD), a condition that can cause developmental delays and autism-like symptoms in children. Research shows it may improve verbal communication and behavior in some children with autism, but it’s not a cure, and it doesn’t work for everyone. If you’re considering leucovorin, work with a psychiatric provider who can evaluate whether your child is a good candidate.
What Is Leucovorin?
Leucovorin is a medication that’s been around for decades. It was originally approved to treat side effects of chemotherapy drugs and a type of anemia. The generic name is folinic acid, and the brand name is Wellcovorin.
What makes leucovorin different from regular folate or folic acid supplements is how it works in the body. It’s already in an active form, which means it doesn’t need to be converted before the body can use it. More importantly, it can reach the brain through an alternate pathway, and that’s the key to why it matters for autism.
Why Is the FDA Updating the Label?
In September 2025, the FDA announced it was working with GSK (the drug’s manufacturer) to expand the Wellcovorin label. The new label will include treatment for cerebral folate deficiency in children, including those with autism-related symptoms.
Here’s why this matters: CFD is a condition where the brain doesn’t get enough folate, even when folate levels in the rest of the body are normal. In some children, this happens because their immune system produces antibodies that block folate from entering the brain through its normal pathway.
The FDA reviewed 23 published studies spanning 2009 to 2024. Across those studies, 85% of patients with CFD showed some form of clinical improvement when treated with leucovorin. The most common improvements were in speech and communication.
Once the label change is finalized, state Medicaid programs and CHIP will be required to cover leucovorin for this use, which is significant, since more than half of all children in the U.S. are insured through those programs.
What Does This Mean for Children with Autism?
This is where it gets nuanced, and where parents need to be careful about what they read online.
The FDA’s label change is specifically for cerebral folate deficiency, not autism broadly. CFD and autism can overlap, but they’re not the same thing. Some children with autism have CFD. Many do not.
Research suggests that folate receptor alpha autoantibodies (FRAAs), the antibodies that can block folate from reaching the brain, are found in roughly 58% to 76% of children with autism. That’s a significant percentage, and it’s one reason researchers believe leucovorin may help a subset of children on the spectrum.
Studies have shown improvements in verbal communication, social interaction, and certain behaviors in children who tested positive for these antibodies. But the research is still limited. Most studies have been small, and results vary from child to child.
The American Academy of Pediatrics published interim guidance for doctors, emphasizing that leucovorin is not a universal treatment for autism and that families should have realistic expectations going in.
How Does Leucovorin Work in the Brain?
In a healthy brain, folate crosses the blood-brain barrier through a transport system called the folate receptor alpha (FRα). This is how the brain gets the folate it needs to function properly.
In children with CFD, autoantibodies block the FRα, cutting off this supply route. Without enough folate in the brain, development can be affected, leading to delays in speech, social skills, and motor function.
Leucovorin works by using a different pathway, the reduced folate carrier (RFC), to get folate into the brain. It essentially bypasses the blockage. When the brain starts receiving adequate folate again, some children experience meaningful improvements.
What the Research Shows (And What It Doesn't)
Here’s what we know so far:
- A randomized, double-blind study of 48 children with autism and language impairment found that those treated with leucovorin for 12 weeks showed greater improvement in verbal communication than the placebo group.
- A systematic review and meta-analysis covering 21 studies found that leucovorin was associated with improvements in communication, attention, and stereotypical behavior, with medium-to-large effect sizes.
- The FDA’s own review of 23 publications found that 85% of CFD patients experienced some form of clinical benefit.
Here’s what we don’t know yet:
- Long-term safety data for leucovorin use in children with autism is limited.
- There is no standardized dosing protocol for this use.
- The AAP notes that we don’t yet have a validated way to measure treatment response over time.
- Results vary significantly; some children show major gains, while others see little to no change.
The NIH has committed to launching confirmatory trials and post-market safety studies to answer these questions.
Is Leucovorin Safe?
Based on decades of use in other medical settings, leucovorin has a generally mild side effect profile. Reported side effects in autism-related studies include increased agitation or excitement (about 12%), insomnia (about 9%), increased aggression (about 10%), headache (about 5%), and increased tantrums (about 6%).
These effects were considered mild in most cases, and no serious adverse effects were attributed to leucovorin treatment in the published research.
That said, leucovorin is a prescription medication that should only be used under medical supervision. Over-the-counter folate supplements are not the same thing and are not a substitute.
Should You Get Your Child Tested?
If you’re considering leucovorin, the first step is a thorough evaluation. Here’s what that typically involves:
A psychiatric evaluation can help determine whether your child’s symptoms align with a condition that might respond to leucovorin. This includes reviewing developmental history, current symptoms, and any previous treatments.
Genetic testing can also play a role. While there’s currently no FDA-approved test for folate receptor autoantibodies specifically, broader pharmacogenetic testing like GeneSight can help guide treatment decisions by identifying how your child’s body processes different medications. At MindWell, we offer genetic testing as part of our approach to personalized psychiatric care.
If leucovorin is appropriate, your provider will establish a dosing plan and a monitoring schedule to track your child’s response over time. Most providers recommend a trial period of at least three to six months before evaluating effectiveness.
You're Not Wrong for Wanting Answers
If you’re a parent of a child with autism, you’ve probably been let down before. Treatments that promised breakthroughs but didn’t deliver. Information that seemed hopeful but turned out to be overhyped.
Leucovorin is not a miracle cure. But for some children, especially those with cerebral folate deficiency or positive folate receptor autoantibodies, it may offer real, measurable improvement. And that’s worth exploring with the right medical team.
The fact that you’re researching this means you’re doing exactly what a good parent does. You’re looking for options, asking questions, and being thoughtful about your child’s care.
How MindWell Can Help
MindWell Psychiatric Services is one of the few practices in Las Vegas that offers leucovorin consultation and guidance. Our provider, Michael Kuron, MSN, APRN, PMHNP, works with families to determine whether leucovorin may be appropriate for their child’s specific situation.
Our approach includes a comprehensive psychiatric evaluation, genetic testing to help guide treatment decisions, and ongoing medication management to monitor progress and adjust dosing as needed.
We accept Medicaid, Medicare, TRICARE, and most major insurance plans. Self-pay options are also available.
Ready to Learn More?
If your child has been diagnosed with autism and you’re wondering whether leucovorin could help, the first step is an evaluation. We can review your child’s history, discuss what the research shows for their specific situation, and help you make an informed decision.
Schedule an appointment with MindWell Psychiatric Services today.
FAQs
Is leucovorin the same as folic acid?
No. Leucovorin is a prescription-grade, active form of folate that can reach the brain through an alternate pathway. Over-the-counter folic acid supplements do not work the same way and are not a substitute.
Is leucovorin FDA-approved for autism?
Not exactly. The FDA is expanding the label to include treatment for cerebral folate deficiency, which can cause autism-like symptoms. The label change is for CFD specifically, though research suggests it may also benefit some children with autism who have folate-related issues.
How long does leucovorin take to work?
Most providers recommend a trial period of three to six months before judging whether it’s effective. Some families notice changes within weeks, while others see gradual improvement over many months.
Does insurance cover leucovorin for autism?
Once the FDA label change is finalized, Medicaid and CHIP programs will be required to cover leucovorin for CFD. Many private insurance plans may also cover it. MindWell can help you verify your coverage before starting treatment.
Are there side effects of leucovorin in children?
Side effects are generally mild. The most commonly reported include agitation, insomnia, headache, and increased tantrums. Serious adverse effects have not been reported in autism-related studies, but treatment should always be supervised by a qualified provider.
How do I know if my child is a good candidate for leucovorin?
A psychiatric evaluation is the best starting point. Your provider can review your child’s symptoms, developmental history, and any prior testing to determine whether leucovorin makes sense as part of their treatment plan.
