PMID- 30217552
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20190529
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 28
IP  - 11
DP  - 2018 Nov
TI  - Effects of high-dose baclofen on cue reactivity in alcohol dependence: A 
      randomized, placebo-controlled pharmaco-fMRI study.
PG  - 1206-1216
LID - S0924-977X(18)30811-3 [pii]
LID - 10.1016/j.euroneuro.2018.08.507 [doi]
AB  - Increased functional brain response towards alcohol-associated stimuli is a 
      neural hallmark of alcohol dependence and a promising target for pharmacotherapy. 
      For the first time, we assessed the effects of individually titrated high-dose 
      baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) 
      patients in a randomized controlled trial (RCT). We investigated 23 recently 
      detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity 
      functional magnetic resonance imaging task. Patients were further scanned at 
      baseline without medication and during treatment with high-dose baclofen/placebo 
      (30-270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, 
      alcohol cue-modulated and stimulus-independent functional connectivity with left 
      ventral tegmental area (VTA) as seed region. At baseline, AD patients (N = 23) 
      showed increased cue-elicited brain activation in the ventral striatum (VS) 
      compared to HC (N = 23), which was decreased at the second scanning session 
      compared to baseline. Patients receiving baclofen (N = 10) showed a significant 
      stronger decrease in cue-elicited brain activation in left orbitofrontal cortex 
      (OFC), bilateral amygdala and left VTA than patients receiving placebo (N = 13). 
      Treatment with baclofen further led to a decrease in alcohol cue-modulated 
      functional connectivity between left VTA and left anterior cingulate cortex (ACC) 
      as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, 
      significantly more patients of the baclofen group remained abstinent during the 
      high-dose period. Baclofen specifically decreased cue-elicited brain responses in 
      areas known to be involved in the processing of salient (appetitive and aversive) 
      stimuli. Treatment with high-dose baclofen seems to provide a pharmacological 
      relief of this neural "warning signal" evoked by alcohol-related cues, thereby 
      possibly supporting patients in remaining abstinent. Trial Registration 
      Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.
CI  - Copyright (c) 2018 Elsevier B.V. and European College of Neuropsychopharmacology. 
      All rights reserved.
FAU - Beck, Anne
AU  - Beck A
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany. Electronic address: 
      anne.beck@charite.de.
FAU - Pelz, Patricia
AU  - Pelz P
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany.
FAU - Lorenz, Robert C
AU  - Lorenz RC
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany; Center for Adaptive 
      Rationality, Max Planck Institute for Human Development, Lentzeallee 94, 14195 
      Berlin, Germany.
FAU - Charlet, Katrin
AU  - Charlet K
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany.
FAU - Geisel, Olga
AU  - Geisel O
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany.
FAU - Heinz, Andreas
AU  - Heinz A
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany.
FAU - Wustenberg, Torsten
AU  - Wustenberg T
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany; Systems Neuroscience 
      in Psychiatry (SNiP), Central Institute of Mental Health, Mannheim, Germany.
FAU - Muller, Christian A
AU  - Muller CA
AD  - Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin Berlin, 
      Campus Charite Mitte, Chariteplatz 1, 10117 Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01266655
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180911
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (GABA-B Receptor Agonists)
RN  - H789N3FKE8 (Baclofen)
SB  - IM
MH  - Adult
MH  - Alcoholism/drug therapy/*physiopathology
MH  - Baclofen/*pharmacology/therapeutic use
MH  - Brain/drug effects/*physiology
MH  - Cues
MH  - Double-Blind Method
MH  - Female
MH  - GABA-B Receptor Agonists/pharmacology/therapeutic use
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neuroimaging
MH  - Ventral Tegmental Area/drug effects/*physiology
MH  - Young Adult
OTO - NOTNLM
OT  - Alcohol dependence
OT  - Baclofen
OT  - Cue reactivity
OT  - fMRI
EDAT- 2018/09/16 06:00
MHDA- 2019/05/30 06:00
CRDT- 2018/09/16 06:00
PHST- 2017/12/29 00:00 [received]
PHST- 2018/07/10 00:00 [revised]
PHST- 2018/08/14 00:00 [accepted]
PHST- 2018/09/16 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2018/09/16 06:00 [entrez]
AID - S0924-977X(18)30811-3 [pii]
AID - 10.1016/j.euroneuro.2018.08.507 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2018 Nov;28(11):1206-1216. doi: 
      10.1016/j.euroneuro.2018.08.507. Epub 2018 Sep 11.