Am Fam Physician. 1998;57(8):1953-1954
Approximately 2 percent of school-aged children in the United States are currently being treated with stimulant medications for attention-deficit hyperactivity disorder (ADHD). These medications have been found to be extremely effective, with response rates of 70 to 96 percent. Mild side effects, including weight loss and insomnia, are frequent and are considered to be dose dependent. To date, studies of the effect of stimulants on children with ADHD have been mainly short term. Two long-term studies did not show clear benefits of stimulant medication in the treatment of ADHD. Gillberg and associates performed a randomized, double-blind study to evaluate the long-term effects of amphetamine use in children with ADHD.
Children enrolled in the study were between six and 11 years of age. Each child was evaluated by a child psychiatrist and a psychologist, and had to meet at least eight of the 14 symptom criteria for ADHD in the Diagnostic and Statistical Manual of Mental Disorders (3d ed rev). Exclusion criteria included an IQ of less than 50 or a chronic medical condition such as diabetes, cardiovascular disease or neurologic disease. At baseline, all children received amphetamine, which was titrated to an effective level over a three-month period. The children were then randomized to receive either amphetamine or placebo for 12 months. This regimen was followed by a three-month period of single-blind placebo treatment. Clinical examination and questionnaires, including the Conners Teacher Rating Scale, Conners Parent Rating Scale and the Wechsler Intelligence Scale for Children–Revised (WISC–R), were performed at baseline and at three-month intervals until the end of the 18-month study period.
A total of 62 children (51 boys, 11 girls) were included in the study. There were no major differences between the two treatment groups. All children responded to stimulants during the first three months of the study with an average decline in Conners rating scores of 27 to 47 percent. During the 12-month double-blind phase, children treated with amphetamine had a significantly greater increase in WISC–R scores at nine months or more compared with the placebo group. Results of the Conners rating scales, which originally declined with treatment in all children, increased up to six months after placebo was given. The Conners rating scores remained lower in the treatment group throughout the duration of the study. Side effects were more common in the amphetamine group but did not differ significantly in terms of incidence. The one exception was a decrease in appetite that occurred in 17 of the children in the treatment group and in two children who received placebo.
During the 12-month double-blind phase of the study, 71 percent of the placebo group and 29 percent of the amphetamine group stopped treatment or went on to open treatment. However, this high rate of withdrawal was anticipated and strongly suggests the superiority of the stimulant drug versus placebo for treating ADHD. Approximately 14 percent of the original cohort of patients were classified as non-responders or dropped out as a result of severe side effects.
The authors conclude that stimulant medications remain effective in the treatment of ADHD for at least 15 months after initiation of therapy. Positive effects include a decrease in hyperactivity and behavior problems, as well as a tendency for improved learning. In addition, side effects do not seem to increase with a longer duration of treatment.