THE USE OF PSYCHOSTIMULANTS IN THE PEDIATRIC PATIENT

The psychostimulant medications have the longest history of medical use in the treatment of childhood psychiatric conditions. Bradley 5 reported the first use of psychostimulant medications in children in 1938. He administered benzedrine (10–20 mg/day) to 30 children aged 5 to 14 years who were hospitalized because of severe behavior disorders. His description 60 years ago of the medication's action in these children is still familiar today: Probably the most striking change in behavior during the week of benzedrine therapy occurred in the school activities of many of these patients. Fourteen children responded in a spectacular fashion. Different teachers, reporting on these patients, who varied in age and school accomplishment, agreed that a great increase of interest in school material was noted immediately. There appeared a definite “drive” to accomplish as much as possible during the school period, and often to spend extra time completing additional work. Speed of comprehension and accuracy of performance were increased in most cases. Insight into school performance was generally present, though few of the children attributed it to the medication they had received earlier in the day. The improvement was noted in all school subjects. It appeared promptly the first day benzedrine was given and disappeared on the first day it was discontinued. 5 Barkley 2 reviewed the early research on psychostimulant drugs in hyperactive children, which by 1977 included many open and double-blind studies and involved hundreds of subjects. Between 1938 and 1974, 15 studies involving 915 children were performed, examining the effectiveness of methylphenidate for the control of hyperactivity. Seventy-seven percent of the subjects were judged to be improved when on methylphenidate. Similar rates of improvement were found for children treated with amphetamines (14 studies, 866 children) and pemoline (2 studies, 105 children). In the eight double-blind, placebo-controlled trials of the three types of psychostimulants, the mean improvement of hyperactive children on the placebo was only 39%. The effect size of psychostimulants can be calculated from such studies to be at approximately 1.0, the largest effect size of any of the psychotropic medications. Despite the long-time use of psychostimulants in treating attention-deficit hyperactivity disorder (ADHD), several questions remain: Are all the psychostimulants interchangeable, or are some children selective responders to a particular psychostimulant? What data are available on Adderall, a mixture of dextroamphetamine and levoamphetamine? Is it a useful addition to other agents for treating ADHD? What research has been done on other long-acting psychostimulants, such as the sustained-release (SR) methylphenidate (Ritalin-SR) or pemoline (Cylert)? What is the best way to dose psychostimulants? Is there a danger of raising the dose “too high” such that improved behavior in fact leads to a decrease in academic productivity (the so-called “zombie effect”)? Is there any way to predict which children with ADHD are most likely to respond to psychostimulants? What side effects are encountered with psychostimulants? In particular, what is the risk for hepatic failure with pemoline? Can children with ADHD with tics be treated safely with psychostimulants? What are the latest data regarding the effects of psychostimulants on growth? The physician who manages children with ADHD must have a thorough understanding of all the issues involved in psychostimulant treatment.