from The Brown University Psychopharmacology Update
Posted 09/24/2002

Presently, the U.S. Food and Drug Administration (FDA) has approved the use of methylphenidate only in children at least six years old. However, many prescribers are using the drug off-label in this population. The 2000 publication of a study documenting dramatic increases in prescriptions for psychotropic medications -- especially methylphenidate (Ritalin and others) -- for preschool-age children attracted a lot of attention -- and not just from child psychiatrists. Even then-First Lady Hillary Clinton raised concern over possible over-prescribing of methylphenidate. "Some of these young people have problems that are symptoms of nothing more than childhood or adolescence," she said. Her call for investigation of the safety of methylphenidate helped pave the way for the Preschool ADHD Treatment Study, the first large-scale study of methylphenidate use in young children.

The original study, by Julie Magno Zito, Ph.D., of the School of Pharmacy at the University of Maryland, and colleagues, analyzed ambulatory care prescription records from two state Medicaid programs and a health maintenance organization (HMO) for the years 1991, 1993 and 1995. The researchers examined prescription trends for stimulants, antidepressants and neuroleptics among children ages two to four years.

Zito and colleagues found that among children between two and four years old, the prevalence per 1,000 enrollees was 12.3 for stimulants, 3.2 for antidepressants, 2.3 for clonidine and 0.9 for neuroleptics. Methylphenidate had a prevalence of 11.1, accounting for 90 percent of stimulant use. Moreover, Zito and colleagues found a substantial increase in psychotropic use among preschoolers during this time period, with a 28.2-fold increase in clonidine use, 3-fold increase in stimulant use and 2.2-fold increase in antidepressant use. Neuroleptic use did not increase substantially during this period.

Zito and colleagues noted in their report that "...randomized, double-blind, controlled clinical trials are needed for off-label indications to evaluate dosages, efficacy, and safety of single and multiple agents shown to be commonly used or widely recommended." They concluded, "Unresolved questions involve the long-term safety of psychotropic medications, particularly in light of earlier age of initiation and longer duration of treatment. While it is reassuring that anecdotal reports have rarely documented these problems, the possibility of adverse effects on the developing brain cannot be ruled out."