Children younger than six years with attention deficit hyperactivity disorder improve with closely monitored use of low-dose methylphenidate, according to an article in the November issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

The first long-term, large-scale study designed to determine the safety
and effectiveness of treating this population found that overall, low doses were both effective and safe. However, researchers also found that children this age are more sensitive than older children to the medication's side effects and therefore should be closely monitored. The 70-week, six-site study was funded by the US National Institutes of Health's National Institute of Mental Health (NIMH).

"The Preschool ADHD Treatment Study, or PATS, provides us with the best
information to date about treating very young children diagnosed with
ADHD," said Thomas R. Insel, MD, of the National Institutes of Health. "The results show that preschoolers may benefit from low doses of medication when it is closely monitored, but the positive effects are less evident and side-effects are somewhat greater than previous reports in older children."

Methylphenidate is the most commonly prescribed medication to treat children diagnosed with the disorder. However, its use for children younger than 6 years has not been approved in the USA. Until the current study, very few studies -- and no large-scale ones -- had been conducted to collect reliable, consistent data to help guide practitioners treating this group of children.

The 303 preschoolers enrolled in the study ranged in age from 3 to 5 years. The children and their parents participated in a pre-trial, 10-week behavioral therapy and training course. Only those children with the most extreme symptoms who did not improve after the behavioral therapy course and whose parents agreed to have them treated with medication were included in the medication study. In the first part of the medication study, children took a range of doses from a very low amount of 3.75 mg daily of methylphenidate, administered in three equal doses, up to 22.5 mg/day. By comparison, doses for school-aged children usually range from 15 to 50 mg total daily.

The study then compared the effectiveness of methylphenidate to placebo. It found that children taking methylphenidate had a more marked reduction of symptoms than children taking a placebo and that different children responded best to different doses.

"The best dose to reduce ADHD symptoms varied substantially among the children, but the average across the whole group was as low as 14 mg per day," said lead author Laurence Greenhill, MD, of Columbia University/New York State Psychiatric Institute. "Preschoolers with ADHD may need only a low dose of methylphenidate initially, but they may need to take a higher dose later on to maintain the drug's effectiveness."

To ensure the safety of the very young children involved, the study was governed by a strict set of ethical standards and additional review boards. The children's health was monitored carefully and repeatedly throughout the study's duration. Parents were repeatedly consulted for consent prior to every step of the program. The researchers also reviewed the teacher ratings of the children who attended preschool at various stages in the study.

Similar to results found in 1999 in the Multimodal Treatment Study of
Children with ADHD and other studies on school-aged children, the medication appeared to slow growth rates. Throughout the duration of the study, children grew about half an inch less in height and weighed about 3 pounds less than expected, based on average growth rates established prior to the study.

Currently, no data exist that track long-term growth rate changes among preschool patients treated with methylphenidate. However, a five-year-long follow-up study is underway to track the children's physical, cognitive, and behavioral development, as well as health care services the family is using to care for the child. Those data will be available in two to three years.

Finally, 89 percent of children tolerated the drug well, but 11 percent dropped out as a result of intolerable side effects. For example, while some children lost weight, weight loss of 10 percent or more of the child's baseline weight was considered a severe enough side effect to discontinue the medication. Other side effects included insomnia, loss of appetite, mood disturbances such as feeling nervous or worried, and skin-picking behaviors. Despite concerns that stimulants may increase blood pressure or pulse, any changes seen in the children's blood pressure or pulse were minimal.

"The study shows that preschoolers with severe ADHD symptoms can benefit from the medication, but doctors should weigh that benefit against the potential for these very young children to be more sensitive than older children to the medication's side effects, and monitor use closely," concluded Dr. Greenhill.

The study was conducted by researchers at Columbia/New York State Psychiatric
Institute, Duke University, Johns Hopkins University, New York University, the University of California Los Angeles, and the University of California Irvine, in collaboration with National Institute of Mental Health staff under a cooperative agreement.