Effects of Modafinil on Neural Correlates of Response Inhibition in Alcohol-Dependent Patients

  • Lianne Schmaal
    Address correspondence to Lianne Schmaal, M.Sc., University of Amsterdam, Department of Psychiatry, Academic Medical Center, P.O. Box 22660, Amsterdam 1100 DD, The Netherlands
    Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • Leen Joos
    Collaborative Antwerp Psychiatric Research Institute, Department of Psychiatry, University of Antwerp, Antwerp, Belgium
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  • Marte Koeleman
    Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • Dick J. Veltman
    Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands
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  • Wim van den Brink
    Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • Anna E. Goudriaan
    Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Arkin Mental Health Care, Amsterdam, The Netherlands
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      Impaired response inhibition is a key feature of patients with alcohol dependence. Improving impulse control is a promising target for the treatment of alcohol dependence. The pharmacologic agent modafinil enhances cognitive control functions in both healthy subjects and in patients with various psychiatric disorders. However, very little is known about the underlying neural correlates of improvements in response inhibition following modafinil.


      We conducted a randomized, double-blind, placebo-controlled, crossover study using functional magnetic resonance imaging with a stop signal task to examine effects of a single dose of modafinil (200 mg) on response inhibition and underlying neural correlates in abstinent alcohol-dependent patients (AD) (n = 16) and healthy control subjects (n = 16).


      Within the AD group modafinil administration improved response inhibition (reflected by the stop signal reaction time [SSRT]) in subjects with initial poor response inhibition, whereas response inhibition was diminished in better performing subjects. In AD patients with initial poor response inhibition, modafinil-induced SSRT improvement was accompanied by greater activation in the thalamus and supplementary motor area (SMA) and reduced connectivity between the thalamus and the primary motor cortex. In addition, the relationship between baseline response inhibition and modafinil-induced SSRT improvement was mediated by these changes in thalamus and SMA activation.


      These findings indicate that modafinil can improve response inhibition in alcohol-dependent patients through its effect on thalamus and SMA function but only in subjects with poor baseline response inhibition. Therefore, baseline levels of response inhibition should be taken into account when considering treatment with modafinil in AD.

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