Efficacy and safety of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder and recent methylphenidate use

Abstract

Introduction: Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations.

Methods: Study 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6-12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP).

Results: In studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use.

Conclusion: In two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.

Fig. 1

Study 1 ADHD-RS-IV total scores for overall study population and prior MPH group. ADHD-RS-IV Attention-Deficit/Hyperactivity Disorder Rating Scale IV, MPH methylphenidate, SD standard deviation

Fig. 2

Study 1 BRIEF GEC T-scores for overall study population and prior MPH group. BRIEF Behavior Rating Inventory of Executive Function, GEC Global Executive Composite, MPH methylphenidate, SD standard deviation

Fig. 3

Study 1 rates of symptomatic remission* for overall study population and prior MPH group. ADHD-RS-IV Attention-Deficit/Hyperactivity Disorder Rating Scale IV, MPH methylphenidate. *Symptomatic remission defined as all ADHD-RS-IV item scores ≤1

Fig. 4

Study 2 ADHD-RS-IV total scores for overall study population and prior MPH group. ADHD-RS-IV Attention-Deficit/Hyperactivity Disorder Rating Scale IV, LDX lisdexamfetamine dimesylate, MPH methylphenidate, SD standard deviation

Fig. 5

Study 2 LS Mean (SE) SKAMP-D (a), SKAMP-A (b), PERMP-A (c), and PERMP-C (d) scores for overall study population and prior MPH group. LDX lisdexamfetamine dimesylate, MPH methylphenidate, PERMP Permanent Product Measure of Performance Attempted (PERMP-A) and Correct (PERMP C), SE standard error, SKAMP Swanson, Kotkin, Agler, M-Flynn, and Pelham Deportment (SKAMP-D) and Attention (SKAMP-A) scale

Fig. 6

Rates of symptomatic remission* for the overall study population and the prior MPH groups. ADHD-RS-IV Attention-Deficit/Hyperactivity Disorder Rating Scale IV, MPH methylphenidate. *Symptomatic remission defined as all ADHD-RS-IV item scores ≤1