The efficacy and safety profile of lisdexamfetamine dimesylate, a prodrug of d-amphetamine, for the treatment of attention-deficit/hyperactivity disorder in children and adults.

BACKGROUND: Lisdexamfetamine dimesylate (LDX) is a once-daily medication approved by the US Food and Drug Administration for the management of attention-deficit/hyperactivity disorder (ADHD) in children (aged 6-12 years) and adults.

OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of LDX.

METHODS: Studies, abstracts, reviews, and consensus statements published in English were identified through computerized searches of MEDLINE (1966-August 2008) and International Pharmaceutical Abstracts (1977-August 2008) using search headings lisdexamfetamine dimesylate, attention-deficit/hyperactivity disorder, NRP 104, NRP104-201, NRP104-301, NRP104-302, NRP104-303, and stimulant. Selected information provided by the manufacturer of LDX was included, as were all pertinent clinical trials. The reference lists of identified articles were also searched for pertinent information. Relevant abstracts presented at annual professional meetings were included as well.

RESULTS: Several studies have evaluated the pharmacokinetics of LDX in pediatric patients (6-12 years of age) and healthy adults with ADHD. LDX, a prodrug that is therapeutically inactive until metabolized in the body to dextroamphetamine (d-amphetamine), follows linear pharmacokinetics at therapeutic doses (30-70 mg). The efficacy of LDX in the treatment of ADHD was established on the basis of 1 long-term and 2 short-term controlled clinical trials in children who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for ADHD (either the combined or the hyperactive-impulsive subtype) and in 1 clinical trial with adults with ADHD. The efficacy trials in children found significant improvements in scores on the Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment sub-scales, the Permanent Product Measure of Performance (Attempted and Correct), and the ADHD Rating Scale Version IV (ADHD-RS-IV) compared with placebo (all, P < 0.001). In the clinical studies designed to measure duration of effect, LDX, compared with placebo, provided efficacy for a full treatment day, up through and including 6 PM, based on parent ratings (Conners' Parent Rating Scale-Revised Short Form) in the morning, afternoon, and early evening (all, P < 0.001). Data from a long-term, open-label extension study that assessed the safety, tolerability, and efficacy of LDX for up to 12 months found LDX treatment resulted in significant improvement (>60%) from baseline in the ADHD-RS-IV at end point (P < 0.001), with good tolerability. The trial in adults found significant improvements in ADHD-RS scores at end point in patients receiving LDX (30,50, and 70 mg) (P < 0.001 for all active doses); significant improvements in ADHD-RS (using adult prompts) scores were observed at each postbaseline weekly assessment, with improvements noted within the first week in all active treatment arms. Results from human abuse liability studies noted that LDX had lower abuse-related drug-liking scores compared with immediate-release d-amphetamine at equivalent doses. The most common adverse events reported with LDX were typical of amphetamine products and included decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea.

CONCLUSIONS: Current evidence supports the efficacy and tolerability of LDX as a treatment option for the management of children (aged 6-12 years) and adults with ADHD. As such, LDX may be an integral part of a total treatment program for ADHD that can include other measures such as psychological, educational, and social interventions.