Date of Graduation

8-15-2009

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mark Pedemonte, MD

Second Advisor

Rob Rosenow PharmD, OD

Third Advisor

Annjanette Sommers MS, PA-C

Abstract

Background: Lisdexamfetamine Dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. Pharmacologically active d-amphetamine is released from Lisdexamfetamine following oral ingestion. It is indicated in the treatment of children ages 6-12 with Attention Deficit Hyperactivity Disorder (ADHD). The goal of LDX is to provide a one dose, extended release medication throughout the day as well as a reduced potential for abuse, overdose toxicity and drug misuse.

Hypothesis: Evaluation of the Efficacy and Tolerability of Lisdexamfetamine Dimesylate (Vyvanse) in Treating Children Age 6-12 with Attention Deficit Hyperactivity Disorder

Study Design: Extensive search of available medical literature and review regarding LDX efficacy and tolerability in children ages 6-12 with ADHD.

Methods: Exhaustive literature search using the following search engines: MEDLINE, Evidence Based Medicine Reviews Multifile, CINAHL, Pub Med, MD Consult, And PsycINFO. The main inclusion criteria were: children age 6-12, patients taking single therapy Lisdexamfetamine dimesylate, primary diagnosis of ADHD based on a psychiatric evaluation that reviews DSM-IV criteria. The exclusion criteria for the study were: comorbid psychiatric diagnoses (such as psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, and severe depressive or severe anxiety disorder), adolescent or adults and patients currently taking alternative amphetamines.

Results: Biederman et al, Study A: Significant improvements in ADHD-RS-IV scores were seen with all doses of LDX compared with placebo (all, P<0.0001), and in CPRS scores with all LDX doses versus placebo throughout the day (all, P<0.0001 for all comparisons). Efficacy was observed by the first week of treatment and improvements were observed throughout the day up to 6pm. Biederman et al, Study B: LDX treatment significantly improved scores on SKAMP-Deportment, and Attention, PERMP attempted and correct and CGI improvement from baseline. Adverse events were similar for both active treatments. Wigal et al, Study C: Compared with placebo, LDX demonstrated significantly greater efficacy at each post-dose time point (1.5 hours to 13 hours), as measured by SKAMP-Deportment and attention scale and PERMP (P < 0.005). The most common adverse effects during dose optimization were: decreased appetite, insomnia, headache, irritability, upper abdominal pain and affect lability, which were less frequent in the crossover phase. Findling et al, Study D: From baseline to endpoints, mean ADHD-RS score improved 27.2 points (P <0.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on CGI improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated “improved”. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or ECG.

Conclusion: In school aged children ages 6-12 with ADHD, LDX a long acting prodrug of D-amphetamine, has been reported to be effective in improving ADHD symptoms throughout the school day and into the early evening with a once daily dose. Additional long term, non bias and comparison studies are needed to evaluate the efficacy and tolerability with prolonged use.

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