title: Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity associated with clinically significant impairment in functioning. ADHD has an early onset, but frequently persists, with a prevalence estimate of 4% in adults. Dasotraline is a novel compound that is a potent inhibitor of dopamine and norepinephrine transporters that achieves stable plasma concentrations with once-daily dosing. In this study, adult outpatients meeting DSM-IV-TR criteria for ADHD were randomized to 4 weeks of double-blind, once-daily treatment with dasotraline 4 and 8 mg/day or placebo. The primary efficacy end point was change from baseline at week 4 in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy end points included the Clinical Global Impression, Severity (CGI-S) scale, modified for ADHD symptoms. Least squares (LS) mean improvements at week 4 in ADHD RS-IV total score were significantly greater for dasotraline 8 mg/day vs placebo (-13.9 vs -9.7; P=0.019), and nonsignificantly greater for 4 mg/day (-12.4; P=0.076). The LS mean improvements in modified CGI-S were significantly greater at week 4 for dasotraline 8 mg/day vs placebo (-1.1 vs -0.7; P=0.013), and for 4 mg/day vs placebo (-1.1 vs -0.7; P=0.021). The most frequent adverse events reported were insomnia, decreased appetite, nausea, and dry mouth. Discontinuations due to treatment-emergent adverse events were 10.3% and 27.8% of patients in 4 and 8 mg/day treatment groups, respectively. This study provides preliminary evidence that once-daily dosing with dasotraline, a long-acting, dual monoamine reuptake inhibitor, may be a safe and efficacious treatment for adult ADHD.
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Koblan
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Seth C
authors.initials: SC
authors.lastname: Hopkins
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Sarma
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Jin
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldman
authors.affiliation: Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.|Sunovion Pharmaceuticals, Fort Lee, NJ, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; C000609455:4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine; D015057:1-Naphthylamine