OBJECTIVES: Lisdexamfetamine dimesylate (LDX), a therapeutically inactive molecule, which after ingestion, is converted to l-lysine, and therapeutically active d-amphetamine, is the first recently approved long-acting (LA) prodrug stimulant indicated for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adults. This study examined adult patients in a US commercial health plan database taking any of 5 long-acting ADHD medications to determine daily average consumption (DACON; pills per day) and ADHD pharmacy costs for LDX compared with other therapies. METHODS: ADHD subjects aged 18-55 years with at least one prescription for atomoxetine (n=513), methylphenidate (n=546), dexmethylphenidate (n=124), mixed amphetamine salts (n=1,514), or LDX (n=246) from July 1, 2007 through October 31, 2007 were studied retrospectively. Subjects were continuously enrolled for 6 months before (baseline) and 6 months after (follow-up) their first qualifying prescription. Subjects with an ICD-9 code for ADHD, but with no ADHD prescriptions at baseline, were retained. Means were compared using student's t-test, proportions using chi-square, and ADHD medication costs in the follow-up period using Wilcoxon Mann Whitney test. RESULTS: The median number of LDX prescriptions (4) and days supplied (113) were highest (p<0.0001) compared with all other medications in the follow-up period. Mean DACON was lowest for LDX (1.06; p<0.0001) and LDX had the highest proportion of patients (87.4%) with a DACON ≤1. Higher DACON was associated with higher median cost for all drugs (p<0.0001 for each), but incremental costs were lowest for LDX. CONCLUSIONS: Compared with four other drugs, LDX users had the lowest DACON, the highest proportion of patients with a DACON ≤1, and longest therapy use in the follow-up period, suggesting both real-world effectiveness and the possibility of better patient compliance with LDX. Supported by funding from Shire Pharmaceutical Development Inc.