The long-term effects of amphetamine sulfate (5 mg AM and lunchtime, increasing to a mean dose of 17 mg/d, 0.52 mg/kg body weight, and a maximum of 45 mg/d) were evaluated in 62 children, aged 6 to 11 years, with ADHD treated for 15 months in a randomized, double-blind, placebo-controlled study at the Child and Adolescent Psychiatry University departments in Goteborg, Uppsala, Malmo-Lund, and Umea, Sweden. Twent six (42%) had comorbid diagnoses, including pervasive developmental disorders, mild retardation, and oppositional defiant disorder. Treatment was stopped or changed to open treatment, usually within 3 months, in 71% of the placebo group and 29% of those receiving amphetamine. Amphetamine was superior to placebo in effects on inattention, hyperactivity, and disruptive behaviors, measured by Conners parent and teacher scores, and on scores on the WISC-R. The mean change in IQ from 0 to >9 months was +4.5 with amphetamine and +0.7 for placebo for 6 months or more. Decreased appetite occurred in 56% of the amphetamine group. Abdominal pain recorded in 32% was no more frequent during amphetamine treatment than placebo. Tics diagnosed before baseline in 4 children were exacerbated during double-blind amphetamine (15 mg/d) in one; 18 developed tics during the study but placebo and amphetamine were equally represented. Visual hallucinations occurred in 3 during amphetamine and required reduction in dose or drug withdrawal. Amphetamine inhibited weight gain but had no significant effect on growth. [1]

COMMENT. Long-term treatment of ADHD with amphetamine may result in improved behavior and learning after 15 months trial, and side effects are generally mild. Trials in ADHD with less comorbidity would be expected to show even greater beneficial effects.

A collaborative multimodal treatment study of children with ADHD, the MTA, is described by NIMH collaborators [2]. It examines long-term effectiveness of medication vs behavioral treatment vs both in 576 children (age, 7-9 years) with ADHD (96 at each of 6 sites) treated for 14 months and reassessed periodically for 24 months. The first patients were enrolled in 1994 and the last will complete the trial in 1998. Pediatric psychopharmacology is receiving a needed boost from this study initiated by the NIMH, and research findings from short-term trials will be tested in more practical, clinically meaningful settings.