Search

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 (Δ height z-score - 0.41 ± 0.55 vs - 0.09 ± 0.58, p = 0.001; Δ 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.

Background: Attention-deficit/hyperactivity disorder (ADHD) is common and may require treatment in adulthood. We aimed to investigate the treatment patterns and perinatal outcomes of women with any history of stimulant treatment for ADHD., Methods: We used health records of the New South Wales (NSW, Australia) population to compare perinatal outcomes of women treated with stimulants (dexamphetamine or methylphenidate) for ADHD from 1982 to 2012 who gave birth between 1994 and 2012, with perinatal outcomes of women with no known ADHD or stimulant treatment (comparison cohort). Five comparison women, matched by maternal age and infant year of birth, were selected for each treated woman. Pregnancy outcome odds ratios in the two groups were adjusted for confounders including maternal age and smoking., Results: Of 5056 women treated for ADHD with stimulant medication, 3351 (66.3%) had stimulant treatment documented before the index pregnancy but not within 1 year before the expected date of delivery, 175 (3.5%) had stimulant treatment before and possibly during pregnancy (stimulant prescription within the 12 months directly before the expected date of the index birth and earlier), and 1530 (30.2%) had no stimulant treatment until after the index pregnancy. Treatment for ADHD at any time (before, before and during and only after the index pregnancy) was associated with reduced likelihood of spontaneous labour-odds ratios (ORs) 0.7 [0.7, 0.8], 0.7 [0.5, 0.9], and 0.7 [0.7, 0.8], respectively-and increased risk of caesarean delivery (1.2 [1.1, 1.3], 1.3 [0.9, 1.8], 1.3 [1.1, 1.4]); active neonatal resuscitation (1.2 [1.0, 1.3], 1.7 [1.1, 2.7], 1.3 [1.0, 1.7]); and neonatal admission > 4 h (1.2 [1.1, 1.3], 1.7 [1.2, 2.4], 1.2 [1.0, 1.4]). Treatment before or before and during pregnancy was, in addition, associated with increased risk of pre-eclampsia (1.2 [1.0, 1.4], 1.5 [0.8, 2.6]); preterm birth < 37 weeks (1.2 [1.0, 1.3], 1.4 [0.9, 2.3]); and 1-min Apgar < 7 (1.2 [1.1, 1.3], 2.0 [1.4, 2.9]). Stimulant prescribing was low during pregnancy (3.5% of women received such a prescription) and dropped during the 12 months before the due date from an average of 24.7 prescriptions per month in the first 6 months to 4.5 per month in the final 6 months., Conclusions: Compared with no treatment, ADHD stimulant treatment at any time was associated with small increases in the risk of some adverse pregnancy outcomes; treatment before, or before and during pregnancy, was associated with additional adverse outcomes, even after a treatment-free period of several years. None of these associations can be confidently attributed to stimulant treatment; in all cases ADHD per se or correlates of it could be responsible for the association.