Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal study design.
OBJECTIVE
In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design.


METHODS
European and US patients (6-17 years; N = 276) with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50, or 70 mg per day) or placebo for a 6-week randomized-withdrawal period (RWP). The primary efficacy measure was the proportion of patients meeting treatment failure criteria (≥50% increase in ADHD Rating Scale IV total score and ≥2-point increase in Clinical Global Impressions-Severity of Illness [CGI-S] score, compared with RWP start point). Safety and tolerability were also evaluated.


RESULTS
During the RWP (LDX, n = 78; placebo, n = 79), significantly fewer patients receiving LDX met treatment failure criteria (15.8%) compared with those receiving placebo (67.5%; difference = -51.7%; 95% confidence interval = -65.0, -38.5; p < .001 ). Most treatment failures occurred at or before the week 2 visit after randomization. Treatment-emergent adverse events were reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the RWP.


CONCLUSIONS
These data demonstrate the maintenance of efficacy of LDX during long-term treatment in children and adolescents with ADHD. The rapid return of symptoms on LDX withdrawal demonstrates the need for continuing treatment. The safety profile of LDX was consistent with that of other stimulants. Clinical trial registration information-Double-Blind, Placebo-Controlled, Randomized Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17; http://clinicaltrials.gov; NCT00784654.
University of Dundee, UK. Electronic address: d.r.coghill@dundee.ac.uk.
David R
DR
Coghill
Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Tobias
T
Banaschewski
Pediatric Sleep Center, Hôpital Universitaire Robert Debré, Paris, France.
Michel
M
Lecendreux
Queen Silvia Children's Hospital, Gothenburg, Sweden.
Mats
M
Johnson
University of Cagliari, Cagliari, Italy.
Alessandro
A
Zuddas
Shire Development LLC, Wayne, PA, USA.
Colleen S
CS
Anderson
Shire Development LLC, Wayne, PA, USA.
Richard
R
Civil
Shire Development LLC, Wayne, PA, USA.
Matthew
M
Dauphin
Shire Development LLC, Wayne, PA, USA.
Nicholas
N
Higgins
Shire Pharmaceutical Development Ltd, Basingstoke, UK.
Andrew
A
Lyne
Shire Development LLC, Wayne, PA, USA.
Maria
M
Gasior
Shire Development LLC, Wayne, PA, USA.
Liza A
LA
Squires
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D017211:Treatment Failure; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000592:standards*
D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
attention-deficit/hyperactivity disorder; central nervous system stimulants; lisdexamfetamine dimesylate; maintenance of efficacy; randomized controlled trial