Modafinil for the Treatment of Alcohol Use Disorders: Targeting Impaired Response Inhibition

Alcohol use disorder (AUD) is a major cause of morbidity and mortality and more treatments are needed, especially pharmacotherapies. There are a variety of efficacious treatments for AUD, but effect sizes are small, and vary from study to study. Medications may be more effective if particular subgroups of AUD are targeted. Identifying the mechanisms of action of a particular medication will help identify the subtypes more likely to respond to therapy. Global impulse control is a rational treatment target, and improving it is a likely mechanisms by which some medications for AUD work, especially in subtypes of AUD with impaired impulse control at baseline. Modafinil is a medication that is FDA approved for the treatment of narcolepsy, and is relatively safe and tolerable. There is reason to believe it may improve impulse control, and underlying neural circuitry, and may work best to improve alcohol use outcomes in AUD with poor impulse control. The overall aim of this study is to investigate the effects of modafinil on task performance and the integrity of neural circuits mediating response inhibition in treatment-seeking AUD with poor response inhibition, to establish target engagement. Secondary aims are to measure whether target engagement mediates improvement in alcohol use outcomes, and to utilize machine learning to identify neural and behavioral markers which best predict treatment outcomes. Twenty-four individuals with AUD and impaired response inhibition will be enrolled in the study, randomized to modafinil or placebo, and treated for 6 weeks. Functional magnetic resonance imaging brain scans during a response inhibition task and during rest will be obtained at baseline and 2 weeks. Aversive stimuli will be included in the response inhibition task to assure that efficacy generalizes to several conditions. Diffusion imaging and arterial spin labeling sequences will also be obtained. Investigators predict that modafinil will significantly increase brain activity in the medial and lateral prefrontal cortex during response inhibition, thereby establishing target engagement, and that it will improve alcohol use outcomes. Findings will provide information about whether or not a larger R01 trial investigating the efficacy of modafinil for individuals with AUD and impaired response inhibition is warranted.