Health-related quality of life and functional outcomes from a randomized, controlled study of lisdexamfetamine dimesylate in children and adolescents with attention deficit hyperactivity disorder

Abstract

Background: Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients' symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.

Objective: The aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.

Methods: Patients (aged 6-17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants' parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome.

Results: The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p < 0.001) in Achievement, 1.079 (p < 0.001) in Risk Avoidance, 0.421 (p < 0.01) in Resilience and 0.365 (p < 0.05) in Satisfaction. In LDX-treated patients, placebo-adjusted improvements from baseline to endpoint in WFIRS-P scores were statistically significant (p < 0.001) for total score and four of the six domains, with effect sizes of 0.924 (total score), 1.249 (Learning and School), 0.730 (Family), 0.643 (Social Activities) and 0.640 (Risky Activities). OROS-MPH treatment showed similar patterns of improvement from baseline to endpoint in both CHIP-CE:PRF and WFIRS-P scores.

Conclusions: Baseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.

Trial registration: ClinicalTrials.gov NCT00763971.

Fig. 1

SPD489-325 study design. ^aScreening and washout (visit −1) was conducted up to 6 weeks before baseline visit (week 0). At visits 1–3 (weeks 1–3), doses were titrated in the indicated single steps to achieve optimal tolerability and efficacy. From visit 4 onwards, doses could not be altered. Child Health and Illness Profile-Child Edition: Parent Report Form and Weiss Functional Impairment Rating Scale-Parent Report assessments were performed at baseline, and then at visits 4 and 7 (shown boxed) and/or at an early termination visit attended by patients who discontinued the trial. LDX lisdexamfetamine dimesylate, OROS-MPH osmotic-release oral system methylphenidate

Fig. 2

Placebo-adjusted changes in CHIP-CE:PRF domain and subdomain T-scores from baseline to endpoint. Histogram shows the LS mean change from baseline to endpoint in CHIP-CE:PRF domain and subdomain T-scores for the LDX and OROS-MPH groups after subtraction of placebo values. Error bars show 95 % confidence intervals. Effect size is the difference in LS mean divided by root-mean-square error. Positive differences indicate improvement compared with placebo. CHIP-CE:PRF Child Health and Illness Profile-Child Edition: Parent Report Form, LDX lisdexamfetamine dimesylate, LS least-squares, OROS-MPH osmotic-release oral system methylphenidate. *p < 0.05, **p < 0.01, ***p < 0.001 vs placebo

Fig. 3

Changes in CHIP-CE:PRF domain T-scores from baseline to study week 4, 7 and endpoint. Circles indicate the LS mean change from baseline in T-scores in the indicated CHIP-CE:PRF domains for the a LDX, b OROS-MPH or c placebo groups. Error bars show 95 % confidence intervals. Numbers of observations (n) are shown for each data point. Positive differences indicate improvement compared with placebo. BL baseline, CHIP-CE:PRF Child Health and Illness Profile-Child Edition: Parent Report Form, EP endpoint, LDX lisdexamfetamine dimesylate, LS least-squares, OROS-MPH osmotic-release oral system methylphenidate, W4 week 4, W7 week 7. *p < 0.05, **p < 0.01, ***p < 0.001 vs baseline

Fig. 4

Placebo-adjusted changes in WFIRS-P domain and total scores from baseline to endpoint. Histogram shows the LS mean change from baseline to endpoint in WFIRS-P domain and total scores for the LDX and OROS-MPH groups after subtraction of placebo values. Error bars show 95 % confidence intervals. Effect size is the difference in LS mean divided by root-mean-square error. Negative differences indicate improvement compared with placebo. LDX lisdexamfetamine dimesylate, LS least-squares, OROS-MPH osmotic-release oral system methylphenidate, WFIRS-P Weiss Functional Impairment Ratings Scale-Parent Report. *p < 0.05, ***p < 0.001 vs placebo

Fig. 5

Change in WFIRS-P scores from baseline to study week 4, 7 and endpoint. Circles indicate the LS mean change from baseline in scores in the indicated WFIRS-P domain or total scores for a LDX, b OROS-MPH or c placebo groups. Error bars show 95 % confidence intervals. Numbers of observations (n) are shown for each data point. Negative differences indicate improvement compared with placebo. BL baseline, EP endpoint, LDX lisdexamfetamine dimesylate, LS least-squares, OROS-MPH osmotic-release oral system methylphenidate, W4 week 4, W7 week 7, WFIRS-P Weiss Functional Impairment Ratings Scale-Parent Report. *p < 0.05, **p < 0.01, ***p < 0.001 vs baseline