Researchers say that an amino acid derivative reduces hyperactivity without the side effects seen with stimulants in boys with Fragile X Syndrome.

by Michael Smith, North American Correspondent, MedPage Today

ROME, Feb. 20 — In boys with fragile X syndrome, an amino acid derivative reduces hyperactivity without the side effects seen with stimulants, researchers here said.

Action Points

  • Explain to interested patients that children with fragile X syndrome are also likely to have ADHD, which is often treated with methylphenidate (Ritalin).
  • Note that methylphenidate has a range of adverse events and many children cannot tolerate the drug.
  • Explain that this study suggests an alternative, non-stimulant medication — L-acetylcarnitine — that appears to control hyperactivity and improve socialization without adverse effects.

L-acetylcarnitine, available in various formulations in the U.S. in health-food stores, significantly reduced attention deficit hyperactivity disorder and improved socialization in a multicenter placebo-controlled randomized trial, found Giovanni Neri, M.D., of the Università Cattolica, and colleagues.

There were no adverse effects associated with the medication, Dr. Neri and colleagues reported online in advance of the April 1 issue of the American Journal of Medical Genetics Part A.

About 73% of boys with fragile X have ADHD, compared with 33% of age- and IQ-matched boys without the syndrome and treatment with methylphenidate (Ritalin) has been shown to be effective, Dr. Neri and colleagues said.

But methylphenidate causes side effects, including increased irritability, decreased verbalization, social withdrawal, and increased stereotypic behavior such as finger picking, that worsen with increasing doses.

For that reason, they said, “alternative pharmacological treatment of ADHD symptoms is desirable.”

A 1999 study showed fragile X boys benefited from the drug, which is approved in Italy for the treatment of mechanical and inflammatory lesions of peripheral nerve trunk or root.

The current study was intended to test the effects of the drug in a larger population.

The researchers randomized 63 patients between the ages of six and 13 to get either placebo or 500 mg twice daily of L-acetylcarnitine for 12 months.

Fifty-six patients completed the study, but five were not included in the analysis because of missing data.

The children were evaluated several times during the study on Conners’ Global Index-Parents and Conners’ Global Index-Teachers, as well as the Vineland Adaptive Behavior Scales.

Some of the patients were also tested genetically to see if the drug had an effect on their mutated FMR1 gene.

The researchers found that both groups improved their behavior — an effect attributed to psychosocial intervention — but the children in the treatment arm had a statistically significant improvement, compared with placebo.

Specifically, over the entire 12-month period:

The Conners’ parents score decreased eight points in the treatment group and 4.4 points in the placebo group. The difference was significant at P0.05 as shown by a F-value of 2.55 obtained by a repeated-measures multivariate analysis.

The Conners’ teacher score fell in both groups but the difference had an F-value of minus 1.74 and was not significant, possibly because not all teachers evaluated their students at all time points.

Treated children did significantly better (P=0.042) than those getting placebo on the Vineland Adaptive Behavior Composite scale, with an F-value of 2.95.

The same was true of the Vineland Socialization scale, with an F-value of 4.37 and P=0.008.

There was no change in IQ at the end of the study, compared with baseline, in either group.

Also, the genetic testing showed no sign that the mutated FMR1 gene had been reactivated, Dr. Neri and colleagues said.

The study confirms that the medication “effectively reduces hyperactive behavior and increases attention in (fragile X syndrome) boys,” Dr. Neri and colleagues concluded.

“We propose that this drug can be recommended as an effective treatment for ADHD in (fragile X syndrome) children, especially those who do not tolerate stimulant drugs,” they said.

The study was supported by the drug’s maker, Sigma-Tau S.p.A., which also supplied L-acetylcarnitine and placebo, as well as the Fondazione TELETHON and PRIN2005. The researchers did not report any potential conflicts.

Primary source: American Journal of Medical Genetics Part A

Source reference: Torrioli MG et al. “A double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys.”Am J Med Genet Part A 2008; 9999: 1-10

Additional resources on this topic:

© MedPage Today, LLC. All Rights Reserved |

Reviewed by Zalman S. Agus, MD; Emeritus Professor, University of Pennsylvania School of Medicine.

Published: February 20, 2008