Paul Newhouse
Last active: 3/3/2020

A randomized, double-blind, placebo-controlled crossover study of α4β 2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder.

Jucaite A, Öhd J, Potter AS, Jaeger J, Karlsson P, Hannesdottir K, Boström E, Newhouse PA, Paulsson B
Psychopharmacology (Berl). 2014 231 (6): 1251-65

PMID: 23640072 · PMCID: PMC3838503 · DOI:10.1007/s00213-013-3116-7

RATIONALE - Stimulation of nicotinic cholinergic systems has been shown to alleviate ADHD symptoms and to improve cognitive performance. AZD1446 is a selective α4β2* nicotinic acetylcholine receptor agonist with potential effect on the symptoms of ADHD.

OBJECTIVES - The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AZD1446 in adults with ADHD treated for 2 weeks.

METHOD - This was a randomized, double-blind, placebo-controlled crossover trial. Participants were 79 adults with ADHD, grouped according to their use of nicotine-containing products. Nicotine non-users received placebo and two of three AZD1446 treatment regimens (80 mg tid, 80 mg qd, 10 mg tid). Nicotine users received placebo, AZD1446 80 mg tid and 80 mg qd. Efficacy measures included the Conners' Adult ADHD Rating Scale and cognitive measures of immediate and delayed verbal episodic memory, learning, attention, working memory, executive functioning, and spatial problem solving (CogState computerized test battery).

RESULTS - There was no significant effect of AZD1446 on any of the clinical scores irrespective of dose, schedule, or concomitant use of nicotine products. A statistically significant improvement was seen on the Groton Maze Learning Task, a measure of executive functioning, in nicotine non-users after treatment with AZD1446 80 mg qd.

CONCLUSIONS - AZD1446 was well tolerated, but did not significantly improve ADHD symptoms after 2 weeks of treatment compared to placebo. While the present study does not support the therapeutic utility of AZD1446 in ADHD, its potential pro-cognitive effects remain to be explored in other neuropsychiatric disorders.

MeSH Terms (19)

Adult Attention Deficit Disorder with Hyperactivity Bridged Bicyclo Compounds, Heterocyclic Cognition Cross-Over Studies Dose-Response Relationship, Drug Double-Blind Method Female Humans Male Middle Aged Neuropsychological Tests Nicotinic Agonists Psychiatric Status Rating Scales Receptors, Nicotinic Time Factors Tobacco Use Disorder Treatment Outcome Young Adult

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