Table 1. . Summary of clinical and pharmacogenetic studies of alcohol use disorder.

Drug	FDA approved for AUD	Clinical summary	Pharmacogenetics summary
Disulfiram	Yes	Disulfiram is an FDA-approved, aversive AUD treatment and data on its clinical effectiveness in decreasing the urge to drink compared with other pharmacotherapy interventions or placebo have been inconsistent	There are only a small number of pharmacogenetic studies examining DBH and ALDH2 genotypes’ moderating effects on disulfiram, all of which were limited by small sample sizes; therefore, larger prospective studies are needed
Naltrexone	Yes	Naltrexone, a μ-opioid receptor antagonist, is the most widely studied FDA-approved AUD medication with demonstrated efficacy	Findings from pharmacogenetic studies have been mixed and it remains unclear to what degree the treatment effect is moderated by genetic variation in the OPRK1, OPRD1 and OPRM1 genes; therefore, reliable large-scale prospective pharmacogenetic clinical trials are needed
Injectable naltrexone	Yes	Injectable naltrexone is a long-acting intramuscular injectable form of naltrexone that appears to be well-tolerated, easy to administer, more likely to increase compliance in patients and efficacious for men	None
Acamprosate	Yes	Acamprosate is an FDA-approved AUD treatment with mixed findings on its efficacy for preventing relapse and promoting abstinence	Acamprosate treatment efficacy may be partially moderated by genetic variation of genes regulating stress and reward pathways, including GATA4, DRD2, GABRA6, GABRB2 and GRIN2B
Topiramate	No	Topiramate is an anticonvulsant medication that is prescribed off-label to treat AUD. There is evidence that topiramate is more efficacious than placebo in treating AUD, and one meta-analysis has demonstrated that it has larger effect sizes than both naltrexone and acamprosate; however, an estimated 20% of patients taking topiramate have dropped out of AUD-related clinical trials of this drug due to its side effects	Data suggest that C-allele homozygous individuals for SNP rs2832407 in GRIK1 are not only more likely to respond beneficially to topiramate than their A-allele counterparts but also experience a lower rate of side effects when receiving topiramate; however, this has not yet been replicated
Gabapentin	No	Gabapentin is an oral anticonvulsant medication that has been prescribed off-label to treat alcohol craving and withdrawal with a favorable safety profile. While there are a small number of clinical trials with data supporting the efficacy of gabapentin for some but not all drinking-related outcome measures, it should be noted that a systematic review has found a risk of misuse of gabapentin for recreational purposes, self-medication or self-harm	None
Baclofen	No	Baclofen is a GABAB receptor agonist that is prescribed off-label for AUD with mixed findings regarding its efficacy	Pharmacogenetic data are limited to date and focused on GABA receptors
Ondansetron	No	Ondansetron is a 5-HT3 receptor antagonist that has been prescribed off-label to reduce alcohol consumption in AUD	Initial data suggest that multiple polymorphisms in the serotonin transporter gene (SLC6A4), as well as in the 5-HT3 receptor gene may moderate treatment response to ondansetron; however, replication in larger clinical trials is required
Varenicline	No	Varenicline is a partial α4β2 nAChR agonist prescribed for smoking cessation and further prescribed off-label for AUD. Initial data suggest that varenicline might be a promising treatment option for AUD, especially in patients with comorbid nicotine use disorder, however, its efficacy for AUD will have to be demonstrated in rigorous clinical trials	None
Nalmefene	No	Nalmefene is a μ- and δ-opioid receptor antagonist and partial κ-opioid receptor agonist that has been approved for the treatment of AUD in the European Union but not in the United States. While some data suggest that nalmefene may have some efficacy in reducing alcohol consumption, there is not enough high-quality data to establish its value for the treatment of AUD; therefore, carefully designed, well-powered randomized controlled trials are needed to compare nalmefene not only to placebo but also to other approved pharmacological AUD treatments	Limited data are available and no effects were found for opioid related genes
SSRIs and serotonin-related drugs	No	Although SSRIs are widely prescribed for the treatment of depression and anxiety, clinical trials examining the efficacy of SSRIs in treating comorbid AUD, depression and anxiety have shown few promising results, and there are few pharmacogenetic studies of these drugs	While some data suggest some genetic moderation of variation in 5-HTTLPR on SSRI efficacy in anxious individuals with AUD, at this time these findings have not been replicated and offer little clinical utility

AUD: Alcohol use disorder; GABA: Gamma-aminobutyric acid; nAChR: Nicotinic acetylcholine receptor; SSRI: Selective serotonin reuptake inhibitor.