Dose Adjustment of Stimulants for Children with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review of the Impact of Exceeding Recommended Doses

摘要

Background When children with attention-deficit/hyperactivity disorder (ADHD) are treated with stimulant medication, the dose is established clinically by dose adjustment over time. Little is known about children who are not adequately treated when they reach a designated maximum dose, or the consequences of exceeding this dose. Objective The aim of this study was to determine the characteristics of and side effects observed in children optimised to high dose (HD) versus regular dose (RD) stimulants. Method Children treated by one paediatrician (AP) in Western Sydney, Australia with HD stimulants (n = 52) were identified using an electronic database; controls on RD stimulant (n = 118) were matched by prescription date with the cases' first HD prescription. HD was defined as methylphenidate > 2 mg/kg/day or > 108 mg/day; dexamphetamine > 1 mg/kg/day or > 50 mg/day; lisdexamfetamine > 70 mg/day. In all children, the dose was adjusted over time to optimise the clinical response. Clinical characteristics, anthropometric measures, reported side effects and reasons for dose changes were extracted from the clinical charts by LR, VS and CS. The HD and RD cohorts were compared using chi-square for categorical data and t tests for continuous data. Results The HD cohort included more boys (88% vs 75%, p = 0.041) and more oppositional defiant disorder (83% vs 55%, p = 0.001). They started stimulants younger (6.40 +/- 1.67 vs 8.28 +/- 2.77 years, p < 0.001) and had more growth attenuation (Delta height z-score - 0.41 +/- 0.55 vs - 0.09 +/- 0.58, p = 0.001; Delta weight z-score - 0.56 +/- 0.82 vs - 0.18 +/- 0.66, p = 0.002). The growth attenuation mainly occurred before the dose reached the HD range. Diminishing stimulant effectiveness was the commonest reason for a dose increase in either cohort, the most prominent recurring symptoms being persistent anger/aggression in the HD and poor concentration in the RD cohort. The commonest reason for dose reduction in the HD cohort was that a dose increase gave no added benefit; dose reduction or change of drug due to subdued/depressed behaviour was more frequent in RD children. Apart from growth attenuation, no serious complications were reported in the HD group. Conclusions In this preliminary study, dose adjustment over time in some patients meant using higher doses than those generally recommended. These children experienced more growth attenuation but recorded no other significant treatment complications. Determining the dose purely on clinical grounds by careful dose adjustment over time appears reasonable, but more data on this issue is required to clarify the efficacy and tolerability of exceeding the recommended doses of stimulants when treating ADHD.