Lisdexamfetamine: A Review in ADHD in Adults

Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine prodrug with a convenient once-daily oral regimen that offers the potential for improved adherence and reduced abuse compared with short-acting preparations of amfetamines. Lisdexamfetamine (as Elvanse Adult(®); Tyvense Adult™) has been approved for use in adults with attention-deficit hyperactivity disorder (ADHD) under the EU decentralization procedure, with the first approvals in the UK, Sweden and Denmark. This approval reflects the results of three short-term trials in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced significantly greater improvements than placebo in ADHD symptoms, overall functioning, executive functioning (including in patients with significant pre-existing impairment) and quality of life. Of note, a post hoc analysis of one of these studies suggested that the response to lisdexamfetamine was generally similar in treatment-naïve patients and those who had already received-and not responded satisfactorily to-previous ADHD therapies, including methylphenidate (MPH). Two further studies demonstrated the longer-term effectiveness of flexible-dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy required ongoing treatment with the drug. Lisdexamfetamine was generally well tolerated in clinical trials, with an adverse event profile typical of that reported for other long-acting stimulants. Head-to-head comparisons with other long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the basis of the available data, lisdexamfetamine provides a useful alternative option for the treatment of adults with ADHD, including those who have not responded adequately to previous ADHD therapies, including MPH.