Lisdexamfetamine dimesylate is a pharmacologically inactive pro-drug that is converted following oral administration to the active metabolite, dexamfetamine. Dexamfetamine is a CNS stimulant that is thought to act by blocking neuronal reuptake of noradrenaline and dopamine.1
Efficacy of lisdexamfetamine mesylate was assessed in a seven-week, double-blind, placebo-controlled study involving 336 patients aged 6–17 years with ADHD of at least moderate severity. Patients were randomised to receive lisdexamfetamine mesylate 30mg once daily (increasing as necessary to max 70mg daily), prolonged-release methylphenidate (Concerta XL) 18mg once daily (increasing as necessary to max 54mg, included as a reference arm to establish assay sensitivity), or placebo.2
Lisdexamfetamine showed significantly greater efficacy than placebo in relieving ADHD symptoms, with a between groups difference in least squares mean change in ADHD rating scale IV (ADHD-RS-IV) total score from baseline to endpoint of -18.6 (p<0.001).2
Lisdexamfetamine also produced significant improvements in functional outcomes compared with placebo, with 78% of patients receiving lisdexamfetamine achieving a Clinical Global Impressions-Global Improvement (CGI-I) score of 1 or 2 compared with 14% of those receiving placebo (p<0.001).2
A randomised double-blind placebo-controlled crossover study in children aged 6–12 years demonstrated that the efficacy of lisdexamfetamine is maintained throughout the day. In the intention to treat analysis (n=113), ADHD symptom scores on the SKAMP deportment scale were significantly lower with lisdexamfetamine than with placebo at 1.5 hours and 13 hours after dosing (p<0.005) and at all timepoints in between. Results on both the SKAMP attention scale and PERMP (a mathematical test used to assess classroom effort) were similar.3
The benefit of continued lisdexamfetamine treatment was shown in a double-blind, placebo-controlled withdrawal study conducted in children and adolescents aged 6–17 years (n=157). After receiving open-label lisdexamfetamine for at least 26 weeks, participants were randomised to continue receiving their optimised dose of lisdexamfetamine or to switch to placebo for six weeks.4
The rate of treatment failure (defined as a ≥50% increase in the ADHD-RS total score and a ≥2-point increase in the CGI severity score) was significantly lower in patients who remained on lisdexamfetamine than in those who switched to placebo (15.8% vs 67.5%, p<0.001).4
Safety and tolerability
The adverse reactions observed in patients treated with lisdexamfetamine reflect those typically associated with stimulant ADHD medication, including decreased appetite, insomnia, dry mouth, headache, weight loss and abdominal pain.1
As with all drugs for ADHD, lisdexamfetamine should only be prescribed as part of a comprehensive treatment programme for the condition. It is not indicated in all children with ADHD and the decision to use the drug must be based on a very thorough assessment of the severity and chronicity of the child’s symptoms in relation to the child’s age and potential for abuse, misuse or diversion.1
Lisdexamfetamine is currently classified as a prescription-only medicine (POM) in the UK. However, the drug’s legal status is scheduled for review by the Home Office and prescribers should be aware that it may be reclassified as a Schedule 2 Controlled Drug (CD) in the future. In the interim, the Royal Pharmaceutical Society is advising pharmacists to treat lisdexamfetamine as if it were a Schedule 2 CD.
- Coghill D et al. Poster presented at 25th Congress of European College of Neuropsychopharmacology. Vienna, Austria, October 2012; P7-009.
Further information: Shire