Children with Autism May See Speech Improvements with Off-Label Prescription Drug

An off-label prescription drug, **leucovorin**, is offering new hope to families of non-verbal children with autism, as it has been shown to help some of these children develop the ability to speak.

Leucovorin is a prescription vitamin that acts like folic acid. It helps restore folate levels in patients who struggle to absorb or use it effectively, explained Katy Dubinsky, a New York pharmacist who co-founded Vitalize, a private supplement company. Though primarily FDA-approved for reducing the toxic effects of high-dose chemotherapy or treating certain types of anemia, some families have turned to it off-label for autism-related communication challenges.

Dr. Richard E. Frye, a behavioral child neurologist in Arizona, has been studying leucovorin in the context of autism spectrum disorder (ASD). He explained that this water-soluble form of vitamin B9 doesn’t build up in the body and has long been deemed safe. "Folates have been considered safe for years, which is why they’re even included in our food supply," Frye said.

The most notable benefit of leucovorin for children with autism, according to Frye, is improved language skills. Other potential gains include enhanced social functioning, reduced repetitive behaviors, and stronger attention spans. “Language is the most obvious improvement we’ve measured in clinical trials," Frye shared, adding that the drug has shown promise for a substantial number of children with autism.

Dr. Marc Siegel, a clinical professor of medicine at NYU Langone Health, elaborated on why the drug may be effective. He pointed to central folate deficiency, a condition where a lack of folate in the brain hinders neurological function. A significant percentage of children with ASD have antibodies that block folic receptor alpha in the brain, making it difficult to process folate through traditional pathways. Leucovorin, however, takes a different route to deliver folate to the brain, potentially improving neurological and communication skills.

Despite these promising findings, experts stress that larger studies are needed. Dr. Siegel noted that smaller studies have been encouraging, but more research is required to establish leucovorin’s efficacy and safety on a broader scale. The drug’s long history of use in chemotherapy treatments, however, provides a solid foundation for understanding its dosage and side effects.

It’s not all smooth sailing, though. Some children reportedly become "extremely hyperactive" or fail to respond to leucovorin, requiring alternative treatments. Frye emphasized that families should consult with knowledgeable medical professionals before exploring leucovorin, given its higher dosing requirements compared to regular vitamins. Testing for abnormalities in the folate pathway, such as folate receptor autoantibodies, is also critical to determining whether a child is a suitable candidate for this treatment.

Many children with autism require a combination of therapies, and leucovorin is not a stand-alone solution. Frye clarified, "It must be used alongside behavioral and speech therapy to enhance outcomes."

Andy Shih, PhD, chief science officer of Autism Speaks, pointed out the need for caution. Every child with autism is unique, and there’s limited evidence to generalize leucovorin’s benefits across the broader autistic community. "Larger, controlled clinical trials are needed to confirm its efficacy," Shih said, urging families to consult with doctors before considering off-label treatments.

Dubinsky echoed the call for more research. If larger studies validate leucovorin’s benefits, it could gain FDA approval for autism treatment, potentially leading to insurance coverage, standardized dosing guidelines, and broader medical acceptance. For now, it remains a promising but experimental option for families seeking to improve their children’s communication skills.