A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder

Harvard University, Cambridge, Massachusetts, United States
Clinical Therapeutics (Impact Factor: 2.73). 02/2006; 28(2):280-93. DOI: 10.1016/j.clinthera.2006.02.008
Source: PubMed


Because the scientific literature on the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) is almost entirely based on the results of studies in samples consisting primarily of boys, much is unknown about the treatment response in girls.
This post hoc analysis compared the efficacy, tolerability, and time course of the effect of mixed amphetamine salts extended release (MAS XR) and atomoxetine in school-age girls with ADHD.
This was an intent-to-treat subanalysis of the data from girls enrolled in a multicenter, 18-day, randomized, double-blind, parallel-group, forced dose-titration, laboratory school study enrolling boys and girls aged 6 to 12 years with ADHD. The study compared the efficacy, tolerability, and time course of the effect of increasing doses of MAS XR (10, 20, and 30 mg/d) and atomoxetine (0.5 and 1.2 mg/kg per day). The laboratory school sessions were organized in cycles to include 12 hours of observation. Efficacy measures included the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) deportment rating subscale, the SKAMP attention rating subscale, and academic testing (number of math problems attempted and answered correctly). Adverse events were assessed throughout the study period. Tolerability and efficacy measures were assessed during laboratory school visits on days 7, 14, and 21.
This subanalysis included 57 girls (median age, 9 years; 49.1% white, 22.8% black, 17.5% Hispanic) with a diagnosis of ADHD, combined subtype. Twenty-six girls were randomized to receive MAS XR and 31 were randomized to receive atomoxetine. Mean SKAMP deportment and attention subscale scores in the 2 groups were similar at baseline. Mean changes from baseline were significantly greater for MAS XR compared with atomoxetine on the SKAMP deportment score (-0.48 vs -0.04, respectively; P<0.001) and SKAMP attention score (-0.45 vs -0.05; P<0.001). The time course of medication effect, based on change from baseline in SKAMP deportment scores, indicated 12-hour efficacy for MAS XR at hours 2, 4.5, 7, 9.5, and 12 (all time points, P<0.01 vs baseline) but not for atomoxetine. At the end of the study, both treatment groups had a significant increase from baseline in the mean number of math problems attempted and answered correctly (P<0.001). Girls who received MAS XR attempted significantly greater numbers of problems compared with those who received atomoxetine (P=0.04). Both MAS XR and atomoxetine were well tolerated. The most frequently occurring treatment-related adverse events in girls receiving MAS XR were decreased appetite (40.7%), upper abdominal pain (29.6%), insomnia (25.9%), and headache (14.8%). The most frequently occurring treatment-related adverse events in girls receiving atomoxetine were somnolence (28.1%), upper abdominal pain (15.6%), vomiting (15.6%), nausea (12.5%), and decreased appetite (12.5%).
This post hoc analysis in a subpopulation of girls with ADHD, combined subtype, found that 18-day treatment with MAS XR was significantly more effective than atomoxetine in terms of ratings of classroom behavior, attention, and academic productivity.

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    • "This agrees with preclinical findings that methylphenidate also markedly enhances catecholaminergic drive in the PFC and striatum (see Heal et al., 2009, 2012). On the other hand, several trials have reported the superior efficacy of amphetamine in the treatment of ADHD in comparison with the non-stimulant, selective noradrenaline reuptake inhibitor, atomoxetine (Strattera®) (Biederman et al., 2006; Faraone et al., 2007; Wigal et al., 2005). This finding fits well with results from in vivo microdialysis experiments that have shown atomoxetine can produce moderate increases in extracellular noradrenaline and dopamine in the PFC as a result of blocking the entry of both catecholamine neurotransmitters into noradrenergic neurones via NET sites, but as a selective noradrenaline reuptake inhibitor it is without effect in other brain regions, such as striatum and nucleus accumbens, where synaptic dopamine concentrations are regulated by DAT sites (Swanson et al., 2006; see also Heal et al., 2009, 2012). "
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