A new paper published in the Journal of the American Association of Children and Adolescent Psychiatry (JAACAP) shows long-term efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit hyperactivity disorder (ADHD).1

Patients with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period were randomized 1:1 to their optimized dose of LDX or placebo for a 6-week randomized withdrawal period (RWP). The long-term study's primary efficacy outcome was the proportion of patients meeting treatment failure criteria by the end of the RWP. Significantly fewer patients receiving LDX met the treatment failure criteria (15.8%) compared to those receiving placebo (67.5%; 95% confidence interval (CI) -65.0, -38.5; p <.001).1 In the placebo group, the return of ADHD symptoms was usually rapid, with most placebo-treated patients who met treatment failure criteria doing so at or before the week two visit following discontinuation of LDX.1

Safety and tolerability were also evaluated with treatment-emergent adverse events reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the randomised withdrawal period.1 The study showed that most treatment-emergent adverse events (TEAEs) were mild or moderate in severity, with only 25 out of 276 (9.1%) individuals reporting severe TEAEs. The most common TEAEs leading to discontinuation were insomnia (8 individuals, 2.9%), aggression (5 individuals, 1.8%), and decreased appetite, headache and depressed mood (each 4 individuals, 1.4%). Adverse events observed with LDX reflected side effects commonly associated with stimulant medications.2

This maintenance of efficacy study (SPD489-326) was conducted in 276 children and adolescents aged 6-17 years with a primary diagnosis of ADHD1 and is the first study to measure long-term efficacy in children and adolescents with ADHD using a randomised-withdrawal design.1 The short-term efficacy of LDX has been established in a series of pivotal randomised, double-blind, placebo-controlled trials.3-7

LDX, the first long-acting prodrug stimulant for the treatment of ADHD, is currently licensed in the UK and eight other European countries for the treatment of children six years of age and over when response to previous methylphenidate treatment is considered clinically inadequate.2

About Study SPD489-3261

  • SPD489-326 is a phase 3 extension study, evaluating the long-term maintenance of efficacy of LDX in children and adolescents with ADHD
  • The study is the first to utilise a randomised-withdrawal design to evaluate the maintenance of efficacy of LDX in children and adolescents with ADHD
  • Of the 276 European and US patients enrolled on the trial, 236 were from study SPD489-325 and were enrolled from 37 sites in Europe (Germany, n=95; Sweden, n=49; Hungary, n=28; Italy, n=20; UK, n=16; France, n=11; Belgium, n=9; Poland, n=8). The remaining 40 patients were directly enrolled from four US sites. At the start of the RWP, 78 patients were randomized to LDX and 79 to placebo. The open-label safety population comprised all 276 enrolled patients, and the randomised safety population comprised all 157 randomised individuals
  • Participants were entered into a 26 week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50 or 70 mg/day) or placebo for a 6-week RWP
  • Treatment failure was measured as a 50% or greater increase in ADHD Rating Scale IV (ADHD-RS- IV) total score and a 2-point or greater increase in Clinical Global Impressions-Severity (CGI-S) score at any double-blind visit relative to the start of the RWP.1