title: Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence.
abstract: 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.
authors.affiliation: Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina 29425, USA. schacht@musc.edu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Schacht
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Randall
authors.forename: L R
authors.initials: LR
authors.lastname: Waid
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Baros
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Latham
authors.forename: Tara M
authors.initials: TM
authors.lastname: Wright
authors.forename: Hugh
authors.initials: H
authors.lastname: Myrick
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Anton
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology; D000588:Amines / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use*; D000077206:Gabapentin; D018698:Glutamic Acid / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018698:Glutamic Acid; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin