Lisdexamfetamine: A prodrug for the treatment of attention-deficit/hyperactivity disorder

Purpose. The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosage, and administration of lisdexamfetamine are reviewed. Summary. Lisdexamfetamine is the first prodrug formulation of the stimulant dextroamphetamine. It is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children age 6-12 years and adults. Due to the need for enzymatic hydrolysis, there is a decreased liability for misuse and diversion with lisdexamfetamine. Moreover, due to the rate-limiting nature of hydrolysis, the toxicity potential and chances of overdose with lisdexamfetamine are reduced. The recommended starting dosage of lisdexamfetamine is 30 mg orally daily, which can be adjusted to a maximum dosage of 70 mg daily. Clinical trials in children age 6-12 years with ADHD found significant reductions in the ADHD symptoms with lisdexamfetamine compared with placebo. However, clinical studies in adolescents have not been conducted. The efficacy and safety of lisdexamfetamine in children with ADHD and comorbid psychiatric disorders also remain to be assessed. A controlled trial in adults similarly showed significant improvements in ADHD symptoms in all treatment groups. Long-term clinical trials and head-to-head comparison trials with existing stimulant formulations are necessary. The most common adverse effects include decreased appetite, insomnia, irritability, dizziness, and weight loss. Conclusion. Clinical trials in children age 6-12 years and adults with ADHD have shown lisdexamfetamine to be safe and effective, with significant improvement of ADHD-related rating scores. However, the efficacy and safety of lisdexamfetamine in children with ADHD and comorbid psychiatric disorders have not been assessed.