ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: Results of a pilot study

Background: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD). Methods: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled. 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conners Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed. Results: A total of 11 adults with well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was superior to placebo for the CAARS Total Symptom Score, which was the primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD Index and Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was observed; however. the dose-response curve for attention and memory effects as measured by computerized cognitive testing seemed dose-linear. No clinically meaningful findings in safety assessments or side effect profile were observed effective in treating adult ADHD and that it is well tolerated. Conclusions: Data from this pilot study suggest that ABT-089 might be effective in treating adult ADHD and that it is well tolerated. On the basis of these promising results, larger, parallel-group ABT-089 studies of longer duration are warranted.