Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.

Trial registration: ClinicalTrials.gov NCT01106430.

Keywords: Atomoxetine; Attention-deficit/hyperactivity disorder; Functional impairment; Lisdexamfetamine dimesylate; Weiss Functional Impairment Rating Scale-Parent Report.

Figures

Fig. 1

Difference between LDX and ATX groups in change in WFIRS-P scores from baseline to endpoint. Histogram shows the difference between treatment groups in LS mean change from baseline to endpoint. Error bars show 95 % confidence intervals. Endpoint was defined as the last on-treatment, post-baseline visit with a valid assessment. Effect size is the difference in LS mean change divided by root mean square error. p values are nominal and were not adjusted for multiple comparisons. *p < 0.05 and **p < 0.01 LDX versus ATX (pre-specified analysis). ATX atomoxetine, LDX lisdexamfetamine dimesylate, LS least-squares, WFIRS-P Weiss Functional Impairment Rating Scale-Parent Report

Fig. 2

Change in WFIRS-P scores from baseline to week 9 and endpoint in (a) the LDX treatment group and (b) the ATX treatment group. The number of observations (n) shows the number of patients with a valid change from BL score at each time point. Endpoint was defined as the last on-treatment, post-baseline visit with a valid assessment. p values are nominal and were not adjusted for multiple comparisons. ***p < 0.001 versus baseline (ad hoc analysis). ATX atomoxetine, BL baseline, CI confidence interval, EP endpoint, LDX lisdexamfetamine dimesylate, LS least-squares, n number of observations, W9 week 9, WFIRS-P Weiss Functional Impairment Rating Scale-Parent Report