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 Conner's 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.


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.
Wilens
Timothy E
TE
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. twilens@partners.org
Verlinden
Marleen H
MH
Adler
Lenard A
LA
Wozniak
Patricia J
PJ
West
Scott A
SA
D000328:Adult; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; C108326:pozanicline