Atomoxetine reduces decisional impulsivity in human cocaine addiction.

Abstract

Background: Impulsivity is a well-known determinant of maladaptive behaviour in cocaine use disorder, 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 health and neuropsychiatric conditions.

Methods: We investigated the effects of atomoxetine on decisional impulsivity in patients with cocaine use disorder. In a randomised, double-blind, placebo-controlled, crossover study, 28 patients diagnosed with moderate-to-severe cocaine use disorder and 28 matched healthy control participants completed the Cambridge Gamble Task in two separate sessions, where they either received placebo or a single dose of 40 mg atomoxetine on each session. Computational modelling was used to decompose decision-making into three separable components: value, probability, and decisional impulsivity.

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

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