Considering a patient’s genetics could inform clinicians which medications would be most effective in controlling cravings and treating alcohol use disorder.
Twenty million Americans currently struggle with an alcohol use disorder. Of those who seek treatment, only 20% receive medications, either alone or in addition to counseling.
Medications are not used more often, according to Charleston Alcohol Research Center scientific director Raymond Anton, M.D., in part because they do not work equally well for everyone.
Many patients with alcohol use disorder would benefit from a personalized medicine approach, in which a medication is prescribed based on a patient’s genetic code.
Anton and his team report in Alcoholism: Clinical and Experimental Research that doing a few relatively simple genetic tests to identify variations in just three brain genes makes it possible to predict which patients with an alcohol use disorder will benefit most from the addiction treatment medication naltrexone.
In previous studies, Anton’s team showed that treating alcohol use disorder with medications that work on specific brain chemicals can reduce the relapse rate by up to a third.
“Alcohol dependence is a brain disease known to affect certain brain chemicals,” said Anton, “So, it’s important to use treatment methods that address not only the behavioral but also the biological/brain components of the problem.”
Naltrexone, a Food and Drug Administration (FDA)-approved addiction medication, is somewhat unique in that it targets just a single protein in the brain -the mu-opioid receptor.
When activated by either an internally produced or externally introduced opioid-like chemical, the mu-opioid receptor signals a positive experience.
Drinking alcohol releases natural opiates in the brain that activate the mu-opioid receptor.
Naltrexone blocks the mu-opioid receptor to prevent the reward and pleasure that comes from drinking alcohol and can even reduce the craving to consume it.
The gene that produces the mu-opioid receptor protein in the brain is not the same in every patient. In the current study, Anton and his team considered the influence of a small gene variation that results in a slight difference in the mu-opioid receptor protein structure.
That slight difference does not affect how people act under normal situations, but it does cause a subtle difference in how strongly the mu-opioid receptor becomes activated when alcohol is consumed, with one variation having a greater response than the other.
Anton and his team hypothesized that this subtle difference in brain chemistry might affect how well naltrexone works in any given patient.
They quickly discovered, however, that the variation in this one gene only did not fully predict how well a patient would respond to the medication.
“There is a small indication that the difference in the mu-opioid receptor gene sequence matters, but it isn’t a powerful predictor,” Anton explained. “People are far more complex than one individual gene variation.
Naltrexone targets this specific mu-opioid receptor, so we hypothesized that the other brain chemicals that might influence the mu-opioid receptor could also influence how the drug might work.”
Dopamine is another reward and pleasure signaling system in the brain that often interacts with the opioid system. Therefore, the amount of dopamine present could influence the mu-opioid receptor and thus the effectiveness of naltrexone.
Anton and his team looked at two such genes that produce proteins controlling the amount of dopamine in the brain.
Like the mu-opioid receptor, these dopamine-processing genes can have small specific variations that result in slight differences in the strength of reward or pleasure signaling after alcohol consumption.
In a clinical trial, Anton and his team genotyped 146 treatment-seeking alcohol use disorder patients for the selected variations in the mu-opioid receptor gene and the two dopamine-processing genes.
A roughly equal number of patients with each gene variation were assigned randomly to receive naltrexone or an identical-looking placebo medication.
Throughout the 16-week trial funded by the National Institutes of Health, patients reported how much they drank each day. A reduction in the number of binge-drinking days, defined as five or more drinks for men or four or more drinks for women, across the study indicated a positive effect of the medication.
Anton and his team found that only patients with certain combinations of gene variations showed consistently reduced drinking when taking naltrexone.
“To benefit most from naltrexone, you have to have the gene variations that predict you’ll be low in one brain chemical response -dopamine or mu-opioid -and high in the other,” Anton explained.
This finding indicates that patients can be genotyped before treatment to see if they will benefit from naltrexone. If they will not benefit, other medications that might be effective are available for them.
Currently, there are no standard genetic screens to test for a patient’s medication response in alcohol/addiction treatment.
Anton and his team are taking the first steps to make genetic predictors a common clinical practice.
They are currently working with the MUSC Foundation for Research Development, MUSC’s technology transfer office, to secure a patent for the discovery that these three genes together predict naltrexone efficacy.
In addition, they are discussing with others the potential of commercial genetic testing to improve the treatment of alcohol use disorder. This is the first step in what could be a wider range of genetic testing for other addictions.
In most regions of the world, most adults consume alcohol at least occasionally (1). Alcohol is among the leading causes of preventable death worldwide, with 3 million deaths per year attributable to alcohol.
In the United States, more than 55% of those aged 26 and older consumed alcohol in a given month, and one in four adults in this age group engaged in binge drinking (defined as more than four drinks for women and five drinks for men on a single drinking occasion) (2).
Excessive alcohol use costs U.S. society more than $249 billion annually and is the fifth leading risk factor for premature death and disability (3).
The morbidity and mortality associated with alcohol are largely due to the high rates of alcohol use disorder in the population. Alcohol use disorder is defined in the Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) (4) as a pattern of alcohol consumption, leading to problems associated with 2 or more of 11 potential symptoms of alcohol use disorder (see Table 1 for criteria).
In the United States, approximately one-third of all adults will meet criteria for alcohol use disorder at some point during their lives (5), and approximately 15.1 million of U.S. adults meet criteria for alcohol use disorder in the previous 12 months (6).
The public health impacts of alcohol use extend far beyond those individuals who drink alcohol, engage in heavy alcohol use, and/or meet criteria for an alcohol use disorder.
Alcohol use is associated with increased risk of accidents, workplace productivity losses, increased medical and mental health costs, and greater rates of crime and violence (1). Analyses that take into account the overall harm due to drugs (harm to both users and others) show that alcohol is the most harmful drug (7).
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
|Difficulties controlling drinking|
(unsuccessful in cutting down
or stopping drinking)
|Neglect of activities||Neglect of activities|
|Time spent drinking or recovering|
from effects of alcohol
|Time spent drinking or recovering|
from effects of alcohol
|Drinking despite physical/|
|Drinking despite physical/|
|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/|
|(Two or more criteria met in past|
|(Three or more criteria met in|
Only a small percent of individuals with alcohol use disorder contribute to the greatest societal and economic costs (8).
For example, in the 2015 National Survey on Drug Use and Health survey (total n = 43,561), a household survey conducted across the United States, 11.8% met criteria for an alcohol use disorder (n = 5124) (6). Of these 5124 individuals, 67.4% (n = 3455) met criteria for a mild disorder (two or three symptoms, based on DSM-5), 18.8% (n = 964) met criteria for a moderate disorder (four or five symptoms, based on DSM-5), and only 13.8% (n = 705) met criteria for a severe disorder (six or more symptoms) (6).
There is a large treatment gap for alcohol use disorder, arising from the fact that many individuals with alcohol use disorder do not seek treatment. Those with a mild or moderate alcohol use disorder may be able to reduce their drinking in the absence of treatment (9) and have a favorable course; but it is those with more severe alcohol use disorder who most often seek treatment and who may experience a chronic relapsing course (10).
NEUROBIOLOGY OF ALCOHOL USE DISORDER
Alcohol use disorder is characterized by loss of control over alcohol drinking that is accompanied by changes in brain regions related to the execution of motivated behaviors and to the control of stress and emotionality (e.g., the midbrain, the limbic system, the prefrontal cortex, and the amygdala).
Mechanisms of positive and negative reinforcement both play important roles with individual drinking behavior being maintained by positive reinforcement (rewarding and desirable effects of alcohol) and/or negative reinforcement mechanisms (negative affective and physiological states that are relieved by alcohol consumption) (15, 16).
At the neurotransmitter level, the positive reinforcing effects of alcohol are primarily mediated by dopamine, opioid peptides, serotonin, γ-aminobutyric acid (GABA), and endocannabinoids, while negative reinforcement involves increased recruitment of corticotropin-releasing factor and glutamatergic systems and down-regulation of GABA transmission (16).
Long-term exposure to alcohol causes adaptive changes in several neurotransmitters, including GABA, glutamate, and norepinephrine, among many others. Discontinuation of alcohol ingestion results in the nervous system hyperactivity and dysfunction that characterizes alcohol withdrawal (15, 16).
Acting on several types of brain receptors, glutamate represents one of the most common excitatory neurotransmitters. As one of the major inhibitory neurotransmitters, GABA plays a key role in the neurochemical mechanisms involved in intoxication, tolerance, and withdrawal. This brief review can offer only a very simplified overview of the complex neurobiological basis of alcohol use disorder. For deeper, more detailed analysis of this specific topic, the reader is encouraged to consult other reviews (15, 16).
CLINICAL MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME
Alcohol withdrawal symptoms may include anxiety, tremors, nausea, insomnia, and, in severe cases, seizures and delirium tremens. Although up to 50% of individuals with alcohol use disorder present with some withdrawal symptoms after stopping drinking, only a small percentage requires medical treatment for detoxification, and some individuals may be able to reduce their drinking spontaneously.
Medical treatment may take place either in an outpatient or, when clinically indicated, inpatient setting. In some cases, clinical monitoring may suffice, typically accompanied by supportive care for hydration and electrolytes and thiamine supplementation.
For those patients in need of pharmacological treatment, benzodiazepines (e.g., diazepam, chlordiazepoxide, lorazepam, oxazepam, and midazolam) are the most commonly used medications to treat alcohol withdrawal syndrome. Benzodiazepines work by enhancing the effect of the GABA neurotransmitter at the GABAA receptor.
Notably, benzodiazepines represent the gold standard treatment, as they are the only class of medications that not only reduces the severity of the alcohol withdrawal syndrome but also reduces the risk of withdrawal seizures and/or delirium tremens.
Because of the potential for benzodiazepine abuse and the risk of overdose, if benzodiazepine treatment for alcohol withdrawal syndrome is managed in an outpatient setting, careful monitoring is required, particularly when combined with alcohol and/or opioid medications (17).
a-2 agonists (e.g., clonidine) and β-blockers (atenolol) are sometimes used as an adjunct treatment to benzodiazepines to control neuro-autonomic manifestations of alcohol withdrawal not fully controlled by benzodiazepine administration (18). However, because of the lack of efficacy of a-2 agonists and β-blockers in preventing severe alcohol withdrawal syndrome and the risk of masking withdrawal symptoms, these drugs are recommended not as monotherapy, but only as a possible adjunctive treatment.
Of critical importance to a successful outcome is the fact that alcohol withdrawal treatment provides an opportunity for the patient and the health care provider to engage the patient in a treatment program aimed at achieving and maintaining long-term abstinence from alcohol or reductions in drinking. Such a treatment may include pharmacological and/or psychosocial tools, as summarized in the next sections.
PHARMACOLOGICAL APPROACHES TO THE TREATMENT OF ALCOHOL USE DISORDER
U.S. Food and Drug Administration–approved pharmacological treatments
Development of novel pharmaceutical reagents is a lengthy, costly, and expensive process. Once a new compound is ready to be tested for human research use, it is typically tested for safety first via phase 0 and phase 1 clinical studies in a very limited number of individuals.
Efficacy and side effects may then be further tested in larger phase 2 clinical studies, which may be followed by larger phase 3 clinical studies, typically conducted in several centers and are focused on efficacy, effectiveness, and safety. If approved for use in clinical practice, this medication is still monitored from a safety standpoint, via phase 4 postmarketing surveillance.
Only three drugs are currently approved by the U.S. Food and Drug Administration (FDA) for use in alcohol use disorder.
The acetaldehyde dehydrogenase inhibitor disulfiram was the first medication approved for the treatment of alcohol use disorder by the FDA, in 1951.
The most common pathway in alcohol metabolism is the oxidation of alcohol via alcohol dehydrogenase, which metabolizes alcohol to acetaldehyde, and aldehyde dehydrogenase, which converts acetaldehyde into acetate.
Disulfiram leads to an irreversible inhibition of aldehyde dehydrogenase and accumulation of acetaldehyde, a highly toxic substance. Although additional mechanisms (e.g., inhibition of dopamine β-hydroxylase) may also play a role in disulfiram’s actions, the blockade of aldehyde dehydrogenase activity represents its main mechanism of action.
Therefore, alcohol ingestion in the presence of disulfiram leads to the accumulation of acetaldehyde, resulting in numerous related unpleasant symptoms, including tachycardia, headache, nausea, and vomiting. In this way, disulfiram administration paired with alcohol causes the aversive reaction, initially proposed as a remedy for alcohol use disorder by Rush (11) in 1784.
One challenge in conducting a double-blind, placebo-controlled alcohol trial of disulfiram is that it is easy to break the blind unless the “placebo” medication also creates an aversive reaction when consumed with alcohol, which would then provide the same mechanism of action as the medication (e.g., the placebo and disulfiram would both have the threat of an aversive reaction).
Open-label studies of disulfiram do provide support for its efficacy, as compared to controls, with a medium effect size (19), as defined by Cohen’s d effect size ranges of small d = 0.2, medium d = 0.5, and large d = 0.8 (20).
The efficacy of disulfiram largely depends on patient motivation to take the medication and/or supervised administration, given that the medication is primarily effective by the potential threat of an aversive reaction when paired with alcohol (21).
The next drug approved for treatment of alcohol use disorder was acamprosate; first approved as a treatment for alcohol dependence in Europe in 1989, acamprosate has subsequently been approved for use in the United States, Canada, and Japan.
Although the exact mechanisms of acamprosate action are still not fully understood, there is evidence that it targets the glutamate system by modulating hyperactive glutamatergic states, possibly acting as an N-methyl-d-aspartate receptor agonist (22).
The efficacy of acamprosate has been evaluated in numerous double-blind, randomized controlled trials and meta-analyses, with somewhat mixed conclusions (23–26). Although a meta-analysis conducted in 2013 (25) indicated small to medium effect sizes in favor of acamprosate over placebo in supporting abstinence, recent large-scale trials conducted in the United States (27) and Germany (28) failed to find effects of acamprosate distinguishable from those of a placebo.
Overall, there is evidence that acamprosate may be more effective in promoting abstinence and preventing relapse in already detoxified patients than in helping individuals reduce drinking (25), therefore suggesting its use as an important pharmacological aid in treatment of abstinent patients with alcohol use disorder.
The most common side effect with acamprosate is diarrhea. Other less common side effects may include nausea, vomiting, stomachache, headache, and dizziness, although the causal role of acamprosate in giving these side effects is unclear.
A third drug, the opioid receptor antagonist naltrexone, was approved for the treatment of alcohol dependence by the FDA in 1994. Later, a monthly extended-release injectable formulation of naltrexone, developed with the goal of improving patient adherence, was also approved by the FDA in 2006.
Naltrexone reduces craving for alcohol and has been found to be most effective in reducing heavy drinking (25). The efficacy of naltrexone in reducing relapse to heavy drinking, in comparison to placebo, has been supported in numerous meta-analyses (23–25), although there is less evidence for its efficacy in supporting abstinence (25).
Fewer studies have been conducted with the extended-release formulation, but its effects on heavy drinking, craving, and quality of life are promising (29, 30). Common side effects of naltrexone may include nausea, headache, dizziness, and sleep problems. Historically, naltrexone’s package insert has been accompanied by a risk of hepatotoxicity, a precaution primarily due to observed liver toxicity in an early clinical trial with administrating a naltrexone dosage of 300 mg per day to obese men (31).
However, there is no published evidence of severe liver toxicity at the lower FDA-approved dosage of naltrexone for alcohol use disorder (50 mg per day). Nonetheless, transient, asymptomatic hepatic transaminase elevations have also been observed in some clinical trials and in the postmarketing period; therefore, naltrexone should be used with caution in patients with active liver disease and should not be used in patients with acute hepatitis or liver failure.
Additional pharmacological treatments approved for alcohol use disorder in Europe
Disulfiram, acamprosate, and naltrexone have been approved for use in Europe and in the United States.
Pharmacologically similar to naltrexone, nalmefene was also approved for the treatment of alcohol dependence in Europe in 2013.
Nalmefene is a m- and d-opioid receptor antagonist and a partial agonist of the k-opioid receptor (32).
Side effects of nalmefene are similar to naltrexone; compared to naltrexone, nalmefene has a longer half-life. Meta-analyses have indicated that nalmefene is effective in reducing heavy drinking days (32). An indirect meta-analysis of these two drugs concluded that nalmefene may be more effective than naltrexone (33), although whether a clinically relevant difference between the two medications really exists is still an open question (34).
Network meta-analysis and microsimulation studies suggest that nalmefene may have some benefits over placebo for reducing total alcohol consumption (35, 36). The approval of nalmefene in Europe was accompanied by some controversy (37); a prospective head-to-head trial of nalmefene and naltrexone could help clarify whether nalmefene has added benefits to the existing medications available for alcohol use disorder.
Last, nalmefene was approved in Europe as a medication that can be taken “as needed” (i.e., on days when drinking was going to occur). Prior work has also demonstrated the efficacy of taking naltrexone only on days that drinking was potentially going to occur (38).
In addition to these drugs, a GABAB receptor agonist used to treat muscle spasms, baclofen, was approved for treatment of alcohol use disorder in France in 2018 and has been used off label for alcohol use disorder for over a decade in other countries, especially in other European countries and in Australia (39, 40).
Recent human laboratory work suggests that baclofen may disrupt the effects of an initial priming dose of alcohol on subsequent craving and heavy drinking (41).
Meta-analyses and systematic reviews examining the efficacy of baclofen have yielded mixed results (35, 39, 42); however, there is some evidence that baclofen might be useful in treatment of alcohol use disorder among individuals with liver disease (43, 44).
Evidence of substantial heterogeneity in baclofen pharmacokinetics among different individuals with alcohol use disorder (41) could explain the variability in the efficacy of baclofen across studies.
The appropriate dose of baclofen for use in treatment of alcohol use disorder remains a controversial topic, and a recent international consensus statement highlighted the importance of tailoring doses based on safety, tolerability, and efficacy (40).
Promising pharmacological treatments
Numerous other medications have been used off label in the treatment of alcohol use disorder, and many of these have been shown to be modestly effective in meta-analyses and systematic reviews (23, 24, 26, 35).
Systematic studies of these medications suggest promising findings for topiramate, ondansetron, gabapentin, and varenicline. The anticonvulsant drug topiramate represents one of the most promising medications in terms of efficacy, based on its medium effect size from several clinical trials [for a review, see (45)], including a multisite clinical study (46).
One strength of topiramate is the possibility of starting treatment while people are still drinking alcohol, therefore serving as a potentially effective treatment to initiate abstinence (or to reduce harm) rather than to prevent relapse in already detoxified patients (45).
Although not approved by the FDA, it is worth noticing that topiramate is a recommended treatment for alcohol use disorder in the U.S. Department of Veterans Affairs (47).
A concern with topiramate is the potential for significant side effects, especially those affecting cognition and memory, warranting a slow titration of its dose and monitoring for side effects.
Furthermore, recent attention has been paid on zonisamide, another anticonvulsant medication, whose pharmacological mechanisms of actions are similar to topiramate but with a better tolerability and safety profile (48).
Recently published and ongoing research focuses on a potential pharmacogenetic approach to treatment in the use of topiramate to treat alcohol use disorder, based on the possibility that both efficacy and tolerability and safety of topiramate may be moderated by a functional single-nucleotide polymorphism (rs2832407) in GRIK1, encoding the kainate GluK1 receptor subunit (49).
Human laboratory studies (50) and treatment clinical trials (51) have also used a primarily pharmacogenetic approach to testing the efficacy of the antinausea drug ondansetron, a 5HT3 antagonist, in alcohol use disorder.
Overall, these studies suggest a potential role for ondansetron in alcohol use disorder, but only in those individuals with certain variants of the genes encoding the serotonin transporter 5-HTT and the 5-HT3 receptor.
The anticonvulsant gabapentin has shown promising results in human laboratory studies and clinical trials (52–54), although a more recent multisite trial with an extended-release formulation of the medication did not have an effect of gabapentin superior to that of a placebo (55).
Although the latter findings might be related to potential pharmacokinetic issues secondary to the specific formulation used, it is nonetheless possible that gabapentin may be more effective in patients with more clinically relevant alcohol withdrawal symptoms (52).
Several human laboratory studies support a role for varenicline, a nicotinic acetylcholine receptor partial agonist approved for smoking cessation, in alcohol use disorder [for a review, see (56)], and two of three clinical trials also support its efficacy on alcohol outcomes (57–59), especially in heavy drinkers who are males (59) and in male and female alcohol-dependent individuals who are also smokers (60).
Additional details on the FDA-approved medications and other medications tested in clinical research settings for the treatment of alcohol use disorder are summarized in 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 dose||Pharmacological mechanism(s) and additional|
|Acamprosate (PO)||1998 mg per day||Unclear—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 day||Inhibition of acetaldehyde dehydrogenase|
|Naltrexone (PO)||50 mg per day||m-opioid receptor antagonist|
|Naltrexone (IM)||380 mg once a month||m-opioid receptor antagonist|
|Not FDA-approved medications tested for alcohol use disorder|
|Baclofen (PO)||30–80 mg per day||GABAB receptor agonist|
|Approved in France by the National Agency for the|
Safety of Medicines and Healthcare Products
|Gabapentin (PO)||900–1800 mg per day||Unclear—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 day||m- 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
|Prazosin/doxazosin (PO)||Up to 16 mg per day||a-1 receptor antagonists|
|Topiramate (PO)||Up to 300 mg per day||Topiramate 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 day||Nicotinic acetylcholine receptor partial agonist|
The medications and targets described above have shown promising results in phase 2 or phase 3 medication trials. However, owing to the development of novel neuroscience techniques, a growing and exciting body of data is expanding the armamentarium of targets currently under investigation in animal models and/or in early-phase clinical studies.
Pharmacological approaches with particular promise for future drug development include, but are not limited to the following [for recent reviews, see, e.g., (56, 61–68)]: the antipsychotic drug aripiprazole, which has multiple pharmacological actions (mainly on dopamine and serotonin receptors), the antihypertensive alpha-1 blocker drugs prazosin and doxazosin, neurokinin-1 antagonism, the glucocorticoid receptor blocker mifepristone, vasopressin receptor 1b antagonism, oxytocin, ghrelin receptor antagonism, glucagon-like peptide-1 agonism, and pharmacological manipulations of the nociception receptor (We are intentionally using a general pharmacological terminology for the nociceptin receptor, given that it is unclear whether agonism, antagonism, or both may represent the best approach.).
New medications development is particularly important for the treatment of comorbid disorders that commonly co-occur among individuals with alcohol use disorder, particularly affective disorders, anxiety disorders, suicidality, and other substance use disorders.
This aspect of alcohol use disorder is relevant to the fact that addictive disorders often present with significantly more severe symptoms when they coexist with other mental health disorders (69). Likewise, there is evidence that pharmacotherapy is most effective when implemented in conjunction with behavioral interventions (70), and all phase 2 and phase 3 medication trials, mentioned above, have included a brief psychosocial behavioral treatment in combination with medication.
More information: Raymond F. Anton et al, Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial, Alcoholism: Clinical and Experimental Research (2020). DOI: 10.1111/acer.14431