Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults.
OBJECTIVE
Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX).


METHODS
Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described.


RESULTS
At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%).


CONCLUSIONS
Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were consistent with those observed with long-term stimulant use.
Brown
Thomas E
TE
Yale Clinic for Attention and Related Disorders, Yale University School of Medicine, 1188 Whitney Ave., PO Box 6694, Hamden, New Haven, CT 06517, USA. tebrownyu@aol.com
Brams
Matthew
M
Gao
Joseph
J
Gasior
Maria
M
Childress
Ann
A
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D056344:Executive Function; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male
D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine