Atomoxetine Reduces Decisional Impulsivity in Human Cocaine Addiction

Abstract

Background: Impulsivity is a well-known determinant of maladaptive behavior in cocaine use disorder (CUD), but there are currently no effective strategies for managing excessive impulsivity. Growing evidence from preclinical and clinical studies suggests that atomoxetine, a selective noradrenaline reuptake inhibitor, is effective in improving impulse control in both healthy individuals and individuals with neuropsychiatric conditions.

Methods: We investigated the effects of atomoxetine on decisional impulsivity in patients with CUD. In a randomized, double-blind, placebo-controlled, crossover study, 28 patients diagnosed with moderate-to-severe CUD and 28 matched healthy control participants completed the Cambridge Gambling Task in 2 separate sessions, where they received either placebo or a single dose of 40 mg atomoxetine at each session. Computational modeling was used to break down decision making into 3 separable components: value, probability, and decisional impulsivity.

Results: Our analyses revealed that patients with CUD were impaired in all components of decision making. Atomoxetine selectively reduced decisional impulsivity in patients with CUD by reducing their risk-seeking tendencies while enhancing their ability to tolerate delays. By contrast, atomoxetine did not affect impulsivity in control participants, but increased their sensitivity to prospective losses.

Conclusions: Taken together, our findings support the hypothesis of noradrenergic dysfunction in patients with CUD and provide novel translational evidence for the efficacy of atomoxetine in remediating decisional impulsivity in CUD.

Keywords: Addictive disorder; Cognitive models; Computational modeling; Decision making; Norepinephrine.