A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD

Abstract

Background: NS2359 is a potent reuptake blocker of noradrenalin, dopamine, and serotonin. The aim of the study was to investigate the efficacy, safety and cognitive function of NS2359 in adults with a DSM IV diagnosis of ADHD.

Methods: The study was a multi-centre, double-blind, randomized placebo-controlled, parallel group design in outpatient adults (18-55 years) testing 0.5 mg NS2359 vs. placebo for 8 weeks. Multiple assessments including computerized neuropsychological evaluation were performed.

Results: There was no significant difference between NS2359 (n = 63) versus placebo (n = 63) on the primary outcome measure reduction in investigator rated ADHD-RS total score (7.8 versus 6.4; p < 0.45). However, in subjects with the inattentive subtype, there were significantly more responders in the NS2359 group compared to placebo (41% versus 7%; p < 0.01). For all secondary variables (ADHD-RS patient rated; The Conners Adult ADHD Scale; The Brown Adult Scale, and CGI-improvement scale) there were no significant differences between the two groups; however, in the inattentive subgroup, the response to treatment was significantly larger than to placebo. NS2359 improved composite factor scores of attention, episodic- and working memory. No serious adverse events were reported with insomnia, headaches and loss of appetite most commonly reported as side effects.

Conclusion: No overall effect of NS2359 was found on overall symptoms of ADHD. There was also a modest signal of improvement in the inattentive adults with ADHD and cognition warranting further exploration using differing doses.

Figure 1

Disposition of Subjects.

Figure 2

Mean Investigator rated ADHD-RS Score (ITT Population) for (a) all Subjects, (b) the ADHD Inattentive Subgroup and (c) the ADHD Combined Subgroup. Active treatment is given week 0 to 8, where week twelve is a follow-up visit.

Figure 3

Change from baseline scores for Quality of Episodic Secondary Memory over the study period (Mean +/- SEM). Improvements from baseline are plotted to ascend.

Figure 4

Change from baseline scores for Power of Attention over the study period (Mean +/- SEM). Improvements from baseline are plotted to ascend.