Advances in the science and treatment of alcohol use disorder

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Science Advances  25 Sep 2019:
Vol. 5, no. 9, eaax4043
DOI: 10.1126/sciadv.aax4043


  • Fig. 1 Conceptual model of factors that affect treatment effectiveness.

    Risk factors proposed in the AARDoC, including incentive salience, negative emotionality, executive function, and social environmental factors, are shown in black bold font encircling alcohol use. Contextual risk factors, including decision-making, self-efficacy, pain, craving, etc., are shown in black font in colored boxes. Risk and protective factors overlap with alcohol use and interact in predicting coping regulation and alcohol use among individual patients.


  • Table 1 Alcohol use disorder criteria, as defined by the Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) (4), and the International Classification of Diseases, 10th edition (ICD-10) (116).

    DSM-5 criteria for alcohol use
    ICD-10 criteria for alcohol
    Difficulties controlling drinking
    (unsuccessful in cutting down or
    stopping drinking)
    Difficulties controlling drinking
    (unsuccessful in cutting down
    or stopping drinking)
    Neglect of activitiesNeglect of activities
    Time spent drinking or recovering
    from effects of alcohol
    Time spent drinking or recovering
    from effects of alcohol
    Drinking despite physical/
    psychological problems
    Drinking despite physical/
    psychological problems
    Alcohol consumed in larger
    amounts or over longer periods
    than was intended
    Failure to fulfill major role
    Recurrent alcohol use in hazardous
    Drinking despite social/
    interpersonal problems
    (Two or more criteria met in past
    (Three or more criteria met in
    past year)
  • Table 2 FDA-approved medications and other medications tested in clinical research settings (phase 2 or 3 medication trials) for the treatment of alcohol use disorder.

    FDA, U.S. Food and Drug Administration; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; PO, per os (oral); IM, intramuscular; HT, serotonin.

    FDA-approved medications for alcohol use disorder
    Daily total dosePharmacological mechanism(s) and additional
    Acamprosate (PO)1998 mg per dayUnclear—it has been suggested that acamprosate is
    a modulator of hyperactive glutamatergic states,
    possibly as an NMDA receptor agonist
    Disulfiram (PO)250–500 mg per dayInhibition of acetaldehyde dehydrogenase
    Naltrexone (PO)50 mg per daym-opioid receptor antagonist
    Naltrexone (IM)380 mg once a monthm-opioid receptor antagonist
    Not FDA-approved medications tested for alcohol use disorder
    Baclofen (PO)30–80 mg per dayGABAB receptor agonist
    Approved in France by the National Agency for the
    Safety of Medicines and Healthcare Products
    Gabapentin (PO)900–1800 mg per dayUnclear—the most likely mechanism is blockade of
    voltage-dependent Ca2+ channels. Although it is a
    GABA analog, gabapentin does not seem to act on
    the GABA receptors
    Nalmefene (PO)18 mg per daym- and d-opioid receptor antagonist and k-opioid
    receptor partial agonist
    Approved in Europe by the European Medicines
    Ondansetron (PO)0.5 mg per day (fixed dose) or up to
    36 mcg/kg per day
    5HT3 antagonist
    Prazosin/doxazosin (PO)Up to 16 mg per daya-1 receptor antagonists
    Topiramate (PO)Up to 300 mg per dayTopiramate is an anticonvulsant with multiple
    targets. It increases GABAA-facilitated neuronal
    activity and simultaneously antagonizes AMPA
    and kainate glutamate receptors. It also inhibits
    l-type calcium channels, limits the activity of
    voltage-dependent sodium channels and
    facilitates potassium conductance. Furthermore, it
    is a weak inhibition of the carbonic anhydrase
    isoenzymes, CA-II and CA-IV
    Varenicline (PO)2 mg per dayNicotinic acetylcholine receptor partial agonist

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