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.


CONCLUSIONS
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.
Wigal
Sharon B
SB
Child Development Center, Department of Pediatrics, University of California, Irvine, Irvine, CA, USA. sbwigal@uci.edu
Jun
Angela
A
Wong
Amanda A
AA
Stehli
Annamarie
A
Steinberg-Epstein
Robin
R
Lerner
Marc A
MA
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D016037:Single-Blind Method; D013599:Systole; D013610:Tachycardia / Q000139:chemically induced / Q000175:diagnosis
D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine