Introduction

Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for treatment of attention-deficit/hyperactivity disorder (ADHD).

Objective

Review efficacy and safety data from two double-blind randomized trials (SPD489-325 and SPD489-326) in patients with ADHD (6–17 years).

Methods

In SPD489-325, patients received placebo, dose-optimized LDX or reference treatment (osmotic-release oral system methylphenidate [OROS-MPH]) for ≤7 weeks. The primary efficacy measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, a ≥26-week open-label LDX treatment period preceded a 6-week, placebo-controlled, randomized-withdrawal period (RWP). The primary endpoint was treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in Clinical Global Impressions-Severity score from RWP baseline). Efficacy was assessed in the full analysis sets.

Results

In SPD489-325 (n=317), placebo-adjusted least-squares-mean changes in ADHD-RS-IV total score from baseline to endpoint were: LDX, –18.6 (95% confidence interval [CI]: –21.5, –15.7; p<0.001; effect size 1.80) and OROS MPH, –13.0 (–15.9, –10.2; p<0.001; 1.26). In SPD489-326 (n=262, open-label period; n=153, RWP), 15.8% and 67.5% of patients receiving LDX and placebo, respectively, met treatment failure criteria at RWP endpoint (difference: –51.7%; 95% CI: –65.0%, –38.5%; p<0.001). Treatment-emergent adverse events occurring in ≥10% of LDX-treated patients were decreased appetite, headache, decreased weight, insomnia, anorexia and nasopharyngitis.

Conclusions

Short-term LDX treatment improved symptoms of ADHD in children and adolescents. Continued LDX treatment was associated with maintenance of efficacy compared with placebo. The LDX safety profile was generally consistent with that of stimulant therapy.

Supported by funding from Shire.