Neurocognitive Performance, Alcohol Withdrawal, and Effects of a Combination of Flumazenil and Gabapentin in Alcohol Dependence
Article first published online: 1 JUN 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 11, pages 2030–2038, November 2011
How to Cite
Schacht, J. P., Randall, P. K., Waid, L. R., Baros, A. M., Latham, P. K., Wright, T. M., Myrick, H. and Anton, R. F. (2011), Neurocognitive Performance, Alcohol Withdrawal, and Effects of a Combination of Flumazenil and Gabapentin in Alcohol Dependence. Alcoholism: Clinical and Experimental Research, 35: 2030–2038. doi: 10.1111/j.1530-0277.2011.01554.x
- Issue published online: 1 NOV 2011
- Article first published online: 1 JUN 2011
- Received for publication June 25, 2010; accepted March 15, 2011.
- γ–Aminobutyric Acid;
Background: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone.
Methods: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial.
Results: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking.
Conclusions: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.