Adverse events in medication treatment-naïve children with attention-deficit/hyperactivity disorder: results from a small, controlled trial of lisdexamfetamine dimesylate.

OBJECTIVE: To evaluate the type, frequency, duration, and severity of treatment emergent adverse events (TEAEs) of the prodrug lisdexamfetamine dimesylate (LDX) in children with and without previous exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: This single-blind, modified laboratory school study used open-label, dose optimization of children aged 6-12 years. LDX, initiated at 30 mg, was dose titrated in 20 mg increments to a possible 70 mg over 4-5 weeks. Safety was assessed using adverse effects and LDX levels. RESULTS: Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n=14 previous stimulant exposure; n=13 stimulant naïve). The stimulant-naïve group reported more trouble sleeping, stomach pain, and hyperfocus, but only previous-exposure subjects experienced dizziness. Previous-exposure subjects showed trends of more decreased appetite, less talkativeness, and less lip sucking. There were no differences in the mean duration of TEAEs. The epidemiological method of percent person-weeks applied to ADHD treatment offers a novel approach to interpreting the pattern of TEAEs. CONCLUSION: LDX reduced the core symptoms of ADHD with more severe adverse events in stimulant-naïve than previous-exposure subjects. Future controlled studies with larger samples should address the impact of previous stimulant exposure on other ADHD treatments.

Does prior exposure to stimulants in children with ADHD impact cardiovascular parameters from lisdexamfetamine dimesylate?

OBJECTIVE: To evaluate the safety profile, based on cardiovascular measurements, of lisdexamfetamine dimesylate (LDX) in children with and without prior exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: This single-blind, modified laboratory school study used open-label dose optimization of children aged 6 to 12 years. Lisdexamfetamine dimesylate, initiated at 30 mg, was dose titrated in 20-mg weekly increments to a possible 70 mg over 4 to 5 weeks. Safety outcomes presented in this study were assessed using vital signs (blood pressure and pulse) and electrocardiograms, conducted at baseline and following LDX treatment. Analyses were performed across all subjects, as well as post hoc based on prior treatment status. In addition, hematologic and blood biochemistry analyses were conducted at baseline but not following treatment. RESULTS: Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n = 14 prior stimulant exposure; n = 13 stimulant naïve). In total, 2 subjects in the stimulant-naïve group experienced changes from baseline vital sign measurements outside the normal range: 1 with tachycardia and 1 with blood pressure ≥ 95th percentile of the normal age range. One other subject in the stimulant-naïve group experienced prolonged QTc in response to LDX, which resolved at follow-up. Pretreatment laboratory work revealed no differences on any parameters when reviewed by exposure subgroup. CONCLUSION: While LDX reduced the core symptoms of ADHD to a similar degree in treatment-naïve and previously treated groups of children with ADHD, more cardiovascular effects were measured in stimulant-naïve children than in children who had previously been exposed to stimulant treatment. Future controlled studies with larger samples should address the impact of prior stimulant exposure on other ADHD treatments.