High Dose L-Methylfolate As Novel Therapy in ADHD

Monday, October 28, 2013
Orlando Ballroom N (Hyatt Regency Orlando, formerly the Peabody)
Robert L. Quillin, MD, The Children's Clinic of Clear Lake, Webster, TX


As of 2007, 9.5% or 4.5 million children (ages 4 to 17 years) have been diagnosed with attention deficit disorders with or without hyperactivity (ADD/ADHD).  The diagnosis of ADD/ ADHD increased an average of 5.5% per year between 2003 and 2007. The cumulative, annual cost of these illnesses is estimated to be between $36 and $52 billion, ranging between $12,005 and $17,458 annually per individual. The exact pathophysiology of ADD/ADHD is not completely understood.  Studies evaluating genetics, environmental factors, and even accuracy of diagnoses suggest multifactorial causes for ADD/ADHD.

Stimulants are currently considered the “gold standard” in the treatment of ADD/ADHD.  Most commonly, these drugs help maintain neurotransmitter balance by regulating the availability of dopamine.  Folate, specifically L-methylfolate, is an important precursor for dopamine synthesis.   As an adjuvant to stimulants, the administration of L-methylfolate can help alleviate the symptoms of ADD/ADHD.


Patients were selected randomly for open label treatment with a high-dose L-methylfolate chewable tablet (0.2 mg/kg/day in a single dose). “High-dose” is considered to be a dose greater than 800 mcg of folate - conventionally available without a prescription.   59 patients were enrolled in the study, aging  5 to 18 years.  The study population included 47 males, 12 females with 27 patients on stimulant therapy and 31 patients not on stimulant therapy.  The Vanderbilt Assessment Scale Total Symptom Score (TSS) was used in scoring of behavioral symptoms at the start of enrollment and again at six weeks.  The starting average TSS score was 30.  All patients were treated with L-methylfolate.


At the end of the six week study period, the average TSS score was 22 (a 27% reduction).  31 patients (53%) exhibited a TSS score reduction of greater than 25%. 16 patients (27%) had a greater than 50% reduction in TSS score.  The patients already on stimulant therapy had an average TSS score of 23 at the end of the study, with 10 patients having an improvement of 49% in TSS score without having to adjust their stimulant dose.  The patients on L-methylfolate alone had an average TSS score of 21 at end of study (34% improvement).  21 of the 32 patients on L-methylfolate alone demonstrated a 53% improvement in their VAS score.


ADD/ADHD can be difficult to manage even with the current stimulant therapies available. L-methylfolate is the naturally occurring metabolite of folate, which is a co-factor that helps to maintain the balance of neurotransmitters. The adjunct use of high-dose L-methylfolate in the susceptible patient represents a therapy not previously explored at a clinical level in ADD/ADHD patients. L-methylfolate potentially represents a novel monotherapy in the treatment of attention deficit disorders. Further studies are warranted to completely understand the therapeutic benefits of L-methylfolate.