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. Author manuscript; available in PMC: 2020 Oct 1.
Published in final edited form as: Alcohol Clin Exp Res. 2019 Aug 23;43(10):2038–2056. doi: 10.1111/acer.14167

Table 1.

AUD Pharmacotherapy studies with Chronic Dosing

First author, year Medication, dose, duration fMRI task Active (Drug) N Control (Placebo) N Population Type Scan Timing Analysis Approach Results Clinical Outcomes
Naltrexone (NTX)
Myrick et al., 2008 50mg NTX × 7 days
0.5mg OND × 7 days
50mg NTX + 0.5mg OND × 7 days		 Visual Alcohol Cues 23
23
20		 24 NTS AD Post Whole Brain and ROI

  • NTX reduced activation to alcohol cues in ventral striatum.

  • OND reduced activation to alcohol cues in ventral striatum.

  • NTX + OND reduced activation to alcohol cues in ventral striatum.

 NS (craving)
NS (craving)
NTX+OND reduced in-scanner craving ratings.
Schacht et al., 2013b 50mg NTX × 6 days Visual Alcohol Cues 35 39 NTS AD Post ROI

  • No significant effect of NTX or OPRM1 genotype on activation in regions of interest: VS, mPFC, OFC.

  • NTX and OPRM1 genotype interacted; NTX-treated G-allele carriers had less OFC activation than A-allele homozygotes.

 NP
Lukas et al., 2013 380mg extended-release NTX (single dose delivered 14 days prior to scanning) Visual and Olfactory Alcohol Cues 15 13 TS Detoxed AD Pre, Post Whole Brain

  • NTX reduced activation in orbital gyri, cingulate, inferior frontal gyrus, and middle frontal gyrus to visual alcohol cues compared to placebo.

  • NTX reduced activation in superior frontal gyrus, supramarginal gyrus, postcentral gyrus, and angular gyrus to alcohol odors compared to placebo.

 XR-NTX reduced in-scanner craving ratings.
Schacht et al., 2017 50mg NTX × 14 days Visual Alcohol Cues 59 57 TS AD Pre, Post ROI

  • NTX reduced right ventral striatal activation to alcohol cues compared to placebo.

 NTX treated individuals with large reductions in pre-post VS activation had less heavy drinking compared to placebo.
Bach et al., 2019 Open-label NTX × 14 days Visual Alcohol Cues 22 13 TS Detoxed AD Pre, Post Whole Brain and ROI

  • NTX reduced alcohol cue-elicited activation in the putamen compared to the non-pharmacological withdrawal treatment group.

 NTX treated individuals with positive cue reactivity in the putamen had a longer time to relapse compared to placebo.
Spagnolo et al., 2014 50mg NTX × 9 days Affective Faces + Alcohol Infusion 31 32 TS AD Post ROI

  • NTX increased activation in ventral striatum to all stimuli compared to placebo.

 NTX + alcohol infusion increased ratings of intoxicated and high compared to placebo.
Varenicline (VAR)
Schacht et al., 2014 2mg varenicline × 14 days Visual Alcohol Cues 18 17 NTS AD Post ROI

  • VAR reduced activation in bilateral OFC compared to placebo.

 NS (heavy drinking and craving)
Vatsalya et al., 2015* 2mg varenicline × 14 days Alcohol Food Incentive Delay Task 17 12 NTS HD Post Whole Brain and ROI

  • VAR reduced activation in striatum, insula, and amygdala during alcohol anticipation compared to placebo.

 NP
Gowin et al., 2016* 2mg varenicline × 14 days Affective Faces + Alcohol Infusion 17 15 NTS HD Post Whole Brain and ROI

  • VAR reduced activation in left amygdala when viewing fearful faces compared to placebo.

 NP
Anticonvulsants (Gabapentin and Baclofen)
Schacht et al., 2013a 1200mg Gabapentin (maximum dose) × 21 days +
2mg infusions of flumazenil × 2 days		 Visual Alcohol Cues 28 20 TS AD Post Whole Brain

  • No significant main effect of medication. In individuals with high levels of alcohol withdrawal GBP increased activation in ACC in response to alcohol cues compared to placebo.

 NS (heavy drinking)
Beck et al., 2018 30–270mg baclofen × 14 days (individually titrated, mean dose = 138mg) Visual Alcohol Cues 10 13 TS Detoxed AD Pre, Post ROI

  • BAC decreased activation in left OFC, bilateral amygdala, and left VTA compared to placebo

 BAC reduced relapse rates.
fMRI + BAC clinical outcomes NP
Holla et al., 2018 60mg baclofen × 17 days Visual Alcohol Cues 23 n/a TS AUD Pre, Post Whole Brain and ROI

  • BAC increased activation in bilateral DLPFC and right ACC, and decreased activation in right insula compared to control group with AUD.

 In BAC-treated individuals, increased ACC activation and decreased insula activation had longer time to alcohol relapse compared to placebo.
Logge et al., 2019 30mg baclofen (low dose) or 74mg baclofen (high dose) × 17 days Visual Alcohol Cues 11 (low dose)
8 (high dose)		 11 TS AD Post Whole Brain

  • No significant group differences for low dose baclofen compared to placebo.

  • High dose BAC decreased activation to alcohol cues in the DLPFC, mPFC, and ACC compared to placebo.

 BAC treatment abolished association between activation in caudate and heavy drinking.
Aripiprazole (APZ)
Myrick et al., 2010 15mg aripiprazole × 14 days Visual Alcohol Cues 14 16 NTS AD Post ROI

  • APZ reduced activation in left VTA and right VS compared to placebo group.

 APZ decreased heavy drinking compared to placebo.
fMRI + AP clinical outcomes NP.
Han et al., 2013 15mg aripiprazole + 20mg Escitalopram × 42 days Video Alcohol Cues 14 17 TS Detoxed AD with comorbid MDD Pre, Post Whole brain

  • APZ + ESC increased activation in left ACC compared to ESC alone.

 APZ + ESC reduced ratings of alcohol craving.
fMRI + AP clinical outcomes NP.
Schacht et al., 2018 15mg aripiprazole × 7 days Visual Alcohol Cues 38 43 NTS AUD Post ROI

  • APZ interacted with DAT1 genotype; in 9R carriers APZ reduced VS activation whereas in 10R homozygotes, APZ increased VS activation to alcohol cues compared to placebo.

 APZ interacted with DAT1 genotype, such that it reduced bar-lab drinking in 9R carriers compared to placebo, but not in 10R homozygotes.
fMRI + AP clinical outcomes NP.
CRF1 Antagonists (Pexacerfont and Verucerfont)
Kwako et al., 2015b 1000mg pexacerfont × 21 days Visual Alcohol Cues
IAPS
Affective Faces		 29 26 TS Detoxed AD Post Whole Brain

  • No significant effect of PEX on alcohol cue reactivity.

  • No significant effect of PEX on neural processing of negative images.

  • No significant effect of PEX on neural processing of affective stimuli.

 NP
Schwandt et al., 2016 350mg verucerfont × 21 days Visual Alcohol Cues
IAPS
Affective Faces		 18 21 TS Detoxed AD Post Whole Brain

  • Mixed effects, VER reduced activation in some frontal, temporal, and occipital regions, and increased activation in other frontal and temporal regions compared to placebo.

  • No significant medication effects.

  • VER reduced activation in right amygdala to fearful faces compared to placebo.

 NP
NK1 Antagonists (LY686017 and Aprepitant)
George et al., 2008 50mg LY686017 × 21 days Visual Alcohol Cues
IAPS		 25 25 TS Detoxed AD Post Whole Brain

  • No significant medication effect.

  • LY686017 reduced activation to negative images in insula and occipital regions compared to placebo.

 LY686017 decreased ratings of craving compared to placebo.
fMRI + LY686017 clinical outcomes NP.
Kwako et al., 2015a 125mg aprepitant × 21 days Visual Alcohol Cues
IAPS
Affective Faces		 26 27 TS Detoxed AD with PTSD Post Whole Brain

  • No significant effects of APREP on neural alcohol cue reactivity.

  • APREP increased activation to negative affective stimuli in bilateral vmPFC compared to placebo.

  • No significant medication effects on activation to affective faces.

 NP
NMDA Modulators (Acamprosate and D-Cycloserine)
Langosch et al., 2012 1998mg acamprosate × 14 days Visual Alcohol Cues 12 10 TS AD Pre, Post Whole Brain and ROI

  • No significant effect of acamprosate on modulating BOLD response to alcohol cues.

 NP
Kiefer et al., 2015 50mg D-cycloserine × 21 days Visual Alcohol Cues 16 16 TS Detoxed AD Pre, Post Whole brain

  • DCS combined with cue-exposure-based extinction training (CET) reduced activation in ventral and dorsal striatum compared to CET alone.

 DCS + CET was more efficacious in individuals with high pre-treatment VS activation and high craving, compared to placebo.

Abbreviations: NTX – naltrexone; OND – ondansetron; VAR – varenicline; GBP – gabapentin; BAC – baclofen; APZ - aripiprazole; PEX – pexacerfont; VER – verucerfont; APREP – aprepitant; DCS – D-cycloserine; TS – treatment seeking; NTS – non-treatment seeking; AD – alcohol dependence (DSM-IV TR diagnosis); AUD – alcohol use disorder (DSM-5 diagnosis); HD – heavy drinker; MDD – major depressive disorder; PTSD – Posttraumatic Stress Disorder; ROI – region of interest; VS – ventral striatum; mPFC – medial prefrontal cortex; OFC – orbitofrontal cortex; ACC – anterior cingulate cortex; VTA – ventral tegmental area; DLPFC – dorsolateral prefrontal cortex; vmPFC – ventromedial prefrontal cortex; NS = non-significant effect of drug on clinical outcomes; NP = clinical outcomes not present.

* =

studies using the same study population